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You are here: Home / Publications / Bibliographies and Resource Guides / Canine Models in Biomedical Research, 1990-2009  / Cardiovascular System  Printer Friendly Page
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Canine Models in Biomedical Research,  1990-2009
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Cardiovascular System

Achour, H.C., F. Boccalandro, M.L. Buja, Y.J. Geng, J. Amirian, P. Felli, and R.W. Smalling (2004). Effects of mechanical left ventricular unloading on endothelin-1 release and apoptosis. Journal of the American College of Cardiology 43(5 Supplement A): 263A-264A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, left anterior descending coronary artery occlusion, lad occlusion, experimental surgical techniques, laboratory techniques, radio immunoassay, immunologic techniques, apoptosis.

Ahlberg, S.E., C.M. Ripplinger, N.D. Skadsberg, P.A. Iaizzo, and L.J. Mulligan (2007). Effects of pacing rate on mechanical restitution within the in vivo canine heart: study of the force-frequency relationship. Journal of Cardiovascular Electrophysiology 18(2): 212-217.
Abstract: INTRODUCTION: It is known that as stimulation frequency is increased in a healthy heart, a corresponding increase in LV contractile function (dP/dt(max)) is observed, i.e., force-frequency relationship. The impact of this relationship on systolic and diastolic mechanical restitution in an ejecting, in vivo preparation has yet to be explored. Understanding this relationship may lead to further insight on the cellular processes that govern the contraction and relaxation of the heart, in addition to providing a safer, more feasible clinical diagnostic tool. METHODS AND RESULTS: Anesthetized canines (n = 8) were paced from the RA at rates of 130, 150, and 180 bpm. At each rate, extrasystoles were delivered at varying intervals. The LV dP/dt(max) and dP/dt(min) associated with the extrasystolic beat were expressed as a percentage of steady-state levels and plotted as a function of the extrasystolic interval to obtain mechanical restitution curves. The systolic restitution time constant length decreased significantly with all increases in heart rate, P < 0.05. In the diastolic case, significant decreases in restitution time constants were seen when heart rate was increased from 130 bpm to 180 bpm, and from 150 bpm to 180 bpm, P < 0.05. CONCLUSION: This study was the first to quantify the finding that the time constant of restitution significantly and consistently decreased with a consistent increase in heart rate. The identification of such behavior may be employed to develop stimulation protocols and chronic diagnostic tools to more safely and sensitively identify and optimize the clinical status of patients receiving pacing therapy.
Descriptors: cardiac pacing, artificial methods, myocardial contraction physiology, biomechanics, blood pressure physiology, diastole physiology, dogs, heart rate physiology, linear models, models, animal, recovery of function physiology, systole physiology.

Akar, F.G., R.C. Wu, I. Deschenes, A.A. Armoundas, V.I. Piacentino, S.R. Houser, and G.F. Tomaselli (2004). Phenotypic differences in transient outward k+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular ito. American Journal of Physiology 286(2 Part 2): H602-H609. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: The Ca2+-independent transient outward K+ current (Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, cardiac disease, western blot analysis, genetic techniques, laboratory techniques, protein chemical techniques, phenotypic differences.

Amado, L., B. Gerber, D.L. Kraitchman, K. Nasir, E. Castillo, B. Rosen, and J.A.C. Lima (2003). Accurate and objective infarct sizing by contrast enhanced magnetic resonance imaging defined in a canine myocardial infarction model. Journal of the American College of Cardiology 41(6 Supplement A): 469A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular medicine, human medicine, medical sciences, methods and techniques, myocardial infarction, heart disease, vascular disease, contrast enchanced magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, positron emission tomography.

Anzai, T., Y. Iino, T. Kumeno, and R. Yozu (2007). Feasibility study of a direct endo-aortic clamp balloon. ASAIO Journal American Society for Artificial Internal Organs 1992 53(2): 136-139.
Abstract: We have developed a new end-aortic clamp balloon catheter intended to be inserted directly into, thereby occluding, the ascending aorta. We examined the performance of this catheter in a canine model. We evaluated the extent of migration tolerance of the catheter under cardiopulmonary bypass perfusion in 12 mongrel dogs, weighing 20 kg, under general anesthesia. After institution of cardiopulmonary bypass, this catheter was inserted into the ascending aorta, and the balloon was inflated to occlude the ascending aorta. After the canine heart was arrested following the administration of cardioplegic solution, balloon migration was examined over a period of 3 hours, with hourly increases in perfusion pressure from 50 mm Hg to 80 mm Hg and finally to 100 mm Hg. After the migration test, ascending aortic wall sections, where the balloon was inflated, were examined microscopically. At internal balloon pressure of 300 to 400 mm Hg, migration occurred at perfusion pressure of > or =90 to 100 mm Hg. No histological differences were observed with use of the balloon catheter, compared with an extra-aortic clamp forceps. Based on these results, this device is safe, feasible, and can adequately occlude the ascending aorta during cardiopulmonary bypass. We conclude that this device is effective in patients weighing 20 kg.
Descriptors: aorta, balloon dilatation instrumentation, monitoring, intraoperative methods, surgical procedures, minimally invasive instrumentation, balloon dilatation adverse effects, catheterization, dogs, feasibility studies, models, animal, monitoring, intraoperative instrumentation, time factors.

Asanuma, H., T. Minamino, S. Sanada, S. Takashima, H. Ogita, A. Ogai, M. Asakura, Y. Liao, Y. Asano, Y. Shintani, J. Kim, Y. Shinozaki, H. Mori, K. Node, S. Kitamura, H. Tomoike, M. Hori, and M. Kitakaze (2004). Beta-adrenoceptor blocker carvedilol provides cardioprotection via an adenosine-dependent mechanism in ischemic canine hearts. Circulation 109(22): 2773-2779. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background - Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts. Methods and Results - In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0 +/- 2.8% versus 40.9 +/- 4.2% in controls), and this effect was completely reversed by the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2 +/- 5.4%) or by an inhibitor of ecto-5'-nucleotidase (44.4 +/- 3.6%). There were no differences of either area at risk or collateral flow among the various groups. When the coronary perfusion pressure was reduced in other dogs so that coronary blood flow was decreased to 50% of the nonischemic level, carvedilol increased coronary blood flow (49.4 +/- 5.6 to 73.5 +/- 7.5 mL cntdot 100 g-1 cntdot min-1; P 0.05) and adenosine release ( 112.3 +/- 22.2 to 240.6 +/- 57.1 nmol/L; P 0.05) during coronary hypoperfusion. This increase of coronary blood flow was attenuated by either 8-sulfophenyltheophylline or superoxide dismutase. In human umbilical vein endothelial cells cultured with or without xanthine and xanthine oxidase, carvedilol caused an increase of ecto-5'-nucleotidase activity. Conclusions - Carvedilol shows a cardioprotective effect against ischemia and/or reperfusion injury via adenosine-dependent mechanisms.
Descriptors: cardiovascular system, transport and circulation, pharmacology, heart ischemia, heart disease, vascular disease, therapy.

Ashikaga, H., B.A. Coppola, B. Hopenfeld, E.S. Leifer, E.R. McVeigh, and J.H. Omens (2007). Transmural dispersion of myofiber mechanics: implications for electrical heterogeneity in vivo. Journal of the American College of Cardiology 49(8): 909-16.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: We investigated whether transmural mechanics could yield insight into the transmural electrical sequence. BACKGROUND: Although the concept of transmural dispersion of repolarization has helped explain a variety of arrhythmias, its presence in vivo is still disputable. METHODS: We studied the time course of transmural myofiber mechanics in the anterior left ventricle of normal canines in vivo (n = 14) using transmural bead markers under biplane cineradiography. In 4 of these animals, plunge electrodes were placed in the myocardial tissue within the bead set to measure transmural electrical sequence. RESULTS: The onset of myofiber shortening was earliest at endocardial layers and progressively delayed toward epicardial layers (p < 0.001), resulting in transmural dispersion of myofiber shortening of 39 ms. The onset of myofiber relaxation was earliest at epicardial layers and most delayed at subendocardial layers (p = 0.004), resulting in transmural dispersion of myofiber relaxation of 83 ms. There was no significant transmural gradient in electrical repolarization (p = NS). CONCLUSIONS: Despite lack of evidence of significant transmural gradient in electrical repolarization in vivo, there is transmural dispersion of myofiber relaxation as well as shortening.
Descriptors: myocardial contraction physiology, ventricular function, left physiology, biomechanics, blood pressure, dogs, electrocardiography, endocardium physiology, models, animal, pericardium physiology.
Notes: Comment In: J Am Coll Cardiol. 2007 Aug 14;50(7):649-50; author reply 650.

Auchampach, J.A., Z.D. Ge, T.C. Wan, J. Moore, and G.J. Gross (2003). A3 adenosine receptor agonist ib-meca reduces myocardial ischemia-reperfusion injury in dogs. American Journal of Physiology 285(2 Part 2): H607-H613. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: We examined the effect of the A3 adenosine receptor (AR) agonist IB-MECA on infarct size in an open-chest anesthetized dog model of myocardial ischemia-reperfusion injury. Dogs were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion and 3 h of reperfusion. Infarct size and regional myocardial blood flow were assessed by macrohistochemical staining with triphenyltetrazolium chloride and radioactive microspheres, respectively. Four experimental groups were studied: vehicle control (50% DMSO in normal saline), IB-MECA (100 mug/kg iv bolus) given 10 min before the coronary occlusion, IB-MECA (100 mug/kg iv bolus) given 5 min before initiation of reperfusion, and IB-MECA (100 mug/kg iv bolus) given 10 min before coronary occlusion in dogs pretreated 15 min earlier with the ATP-dependent potassium channel antagonist glibenclamide (0.3 mg/kg iv bolus). Administration of IB-MECA had no effect on any hemodynamic parameter measured including heart rate, first derivative of left ventricular pressure, aortic pressure, LAD coronary blood flow, or coronary collateral blood flow. Nevertheless, pretreatment with IB-MECA before coronary occlusion produced a marked reduction in infarct size (apprx40% reduction) compared with the control group (13.0+-3.2% vs. 25.2+-3.7% of the area at risk, respectively). This effect of IB-MECA was blocked completely in dogs pretreated with glibenclamide. An equivalent reduction in infarct size was observed when IB-MECA was administered immediately before reperfusion (13.1+-3.9%). These results are the first to demonstrate efficacy of an A3AR agonist in a large animal model of myocardial infarction by mechanisms that are unrelated to changes in hemodynamic parameters and coronary blood flow. These data also demonstrate in an in vivo model that IB-MECA is effective as a cardioprotective agent when administered at the time of reperfusion.
Descriptors: animal model, myocardial ischemia-reperfusion injury, myocardial blood flow, infarct size, coronary occlusion, A3 adenosine receptor, IB-MECA, cardioprotective agent, pharmacology, coronary occlusion, drug therapy, aortic pressure, coronary blood flow, coronary collateral blood flow, heart rate, infarct size, left ventricular pressure.

Auchampach, J.A., X. Jin, J. Moore, T.C. Wan, L.M. Kreckler, Z.D. Ge, J. Narayanan, E. Whalley, W. Kiesman, B. Ticho, G. Smits, and G.J. Gross (2004). Comparison of three different a1 adenosine receptor antagonists on infarct size and multiple cycle ischemic preconditioning in anesthetized dogs. Journal of Pharmacology and Experimental Therapeutics 308(3): 846-856. ISSN: 0022-3565.
NAL Call Number: 396.8 J82
Abstract: A1 adenosine receptor (AR) antagonists are effective diuretic agents that may be useful for treating fluid retention disorders including congestive heart failure. However, antagonism of A1ARs is potentially a concern when using these agents in patients with ischemic heart disease. To address this concern, the present study was designed to compare the actions of the A1AR antagonists CPX (1,3-dipropyl-8-cyclopentylxanthine), BG 9719 (1,3-dipropyl-8-(2-(5,6-epoxynorbomyl))xanthine), and BG 9928 (1,3-dipropyl-8-(1-(4-propionate)-bicyclo-(2,2,2)octyl)xanthine) on acute myocardial ischemia/reperfusion injury and ischemic preconditioning (IPC) in an in vivo dog model of infarction. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion, after which infarct size was assessed by staining with triphenyltetrazolium chloride. IPC was elicited by four 5-min occlusion/5-min reperfusion cycles produced 10 min before the 60-min occlusion. Multiple-cycle IPC produced a robust reduction (apprx65%) in infarct size; this effect of IPC on infarct size was not abrogated in dogs pretreated with any of the three AR antagonists. Surprisingly, in the absence of IPC, pretreatment with CPX or BG 9928 before occlusion or immediately before reperfusion resulted in significant reductions (apprx40-50%) in myocardial infarct size. However, treatment with an equivalent dose of BG 9719 had no similar effect. We conclude that the A1AR antagonists BG 9719, BG 9928, and CPX do not exacerbate cardiac injury and do not interfere with IPC induced by multiple ischemia/reperfusion cycles. We discuss the possibility that the cardioprotective actions of CPX and BG 9928 may be related to antagonism of A2BARs.
Descriptors: cardiovascular system, transport and circulation, pharmacology, acute myocardial ischemia, reperfusion injury, heart disease, injury, vascular disease, ischemic preconditioning.

Baba, S., W. Dun, and P.A. Boyden (2003). Can pka activators restore na+ channel function in cells from the canine infarcted heart? Biophysical Journal 84(2 Part 2): 549A. ISSN: 0006-3495.
NAL Call Number: 442.8 B5238
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, membranes, cell biology, myocardial infarction, heart disease, vascular disease, patch clamp, histology and cytology techniques, laboratory techniques.

Bal, H., E.V. Dibella, and G.T. Gullberg (2003). Myocardial assessment with dynamic teboroxime spect in a reperfused canine model. Journal of Nuclear Medicine 44 (5 Supplement): 113P. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, cardiac single photon emission computed tomography imaging, imaging and microscopy techniques, laboratory techniques, myocardial assessment, myocardial blood flow, myocardial viability.

Banerjee, D.D., M.S. Quinn, L.B. Mohanty, and A.J. Minisi (2008). Failure of chronic transmyocardial laser revascularization to alter cardiac nociceptive reflexes: implications for the treatment of angina pectoris. Lasers in Medical Science 23(2): 155-61. ISSN: 0268-8921.
Abstract: The aim of this study was to assess the delayed effects of transmyocardial laser revascularization (TMLR) on cardiac nociceptors. Experiments were performed in anesthetized dogs 1 month after thoracotomy with either TMLR (n = 17) or sham laser procedure (n = 17). All dogs underwent sinoaortic denervation and vagotomy to isolate the sympathetic afferent system. Left ventricular sympathetic afferents were stimulated by intracoronary bradykinin and transmural myocardial ischemia. Efferent responses were measured by direct recording of renal sympathetic nerve activity. Renal nerve responses to intracoronary bradykinin administered to the laser-treated anterior ventricular wall were not significantly different from those observed from the unlased posterior wall. Anterior transmural ischemia elicited similar renal nerve responses in laser-treated and sham groups. Pathologic analysis showed intact neural structures in the subepicardial regions both near and remote from the lased channels. We conclude that reflexes mediated by left ventricular sympathetic afferents are preserved after chronic TMLR. These findings do not support the neural hypothesis for angina relief.
Descriptors: angina pectoris therapy, heart innervation, heart ventricles innervation, laser therapy methods, nociceptors radiation effects, treatment failure, chronic disease, dogs, heart physiology, laser therapy instrumentation, models, animal, myocardial ischemia therapy, myocardium, sympathetic nervous system, thoracotomy, time factors, ventricular function.

Banyasz, T., L. Fulop, J. Magyar, N. Szentandrassy, A. Varro, and P.P. Nanasi (2003). Endocardial versus epicardial differences in l-type calcium current in canine ventricular myocytes studied by action potential voltage clamp. Cardiovascular Research 58(1): 66-75. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: Objectives: The aim of the present study was to assess and compare the dynamics of L-type Ca2+ current (ICa,L) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin. Methods: ICa,L was recorded on cells derived from the two regions of the heart using both AP voltage clamp and conventional whole cell voltage clamp techniques. Results: AP voltage clamp experiments revealed that the decay of ICa,L is monotonic during endocardial AP, whereas the current is double-peaked (displaying a second rise) during epicardial AP. The amplitude of the first peak was significantly greater in ENDO (-4.6+-0.8 pA/pF) than in EPI cells (-2.8+-0.3 pA/pF). Application of epicardial APs as command pulses to endocardial cells yielded double-peaked ICa,L profiles, and increased the net charge entry carried by ICa,L during the AP from 0.187+-0.059 to 0.262+-0.056 pC/pF (n=5, P<0.05). No differences were observed in current densities and inactivation kinetics of ICa,L between EPI and ENDO cells when studied under conventional voltage clamp conditions. Nisoldipine shortened action potentials and eliminated the dome of the epicardial AP. Conclusion: ICa,L was shown to partially inactivate before and deactivate during phase-1 repolarization and reopening of these channels is responsible for the formation of the dome in canine EPI cells. The transmural differences in the profile of ICa,L could be well explained with differences in AP configuration.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, cell biology, methods and techniques, action potential.

Bashar, A.H., K. Suzuki, T. Kazui, M.Y. Okada, T. Suzuki, N. Washiyama, H. Terada, and K. Yamashita (2008). Changes in cerebrospinal fluid and blood lactate concentrations after stent-graft implantation at critical aortic segment: a preliminary study. Interactive Cardiovascular and Thoracic Surgery 7(2): 262-6.
Abstract: OBJECTIVES: Obstruction of blood flow through the arteria radicularis magna (ARM) has been linked with ischemic spinal cord injury after conventional thoracic aortic repair. Whether or not endoluminal stent-grafts, deliberately positioned against this artery can cause similar damage to the spinal cord has not been comprehensively investigated. The purpose of this study was to assess the blood and cerebrospinal fluid (CSF) concentrations of lactate - a well-known biochemical marker of ischemic neurological injury, before and after stent-graft implantation against the ARM. MATERIALS AND METHODS: Endoluminal stent-grafting was performed in ten mongrel dogs. In five animals (experimental group), stent-grafts covered the fourth and fifth lumbar segmental arteries - which have been described as the canine equivalents to the ARM in humans. In the remaining five animals (control group), devices of similar length were placed in the lower thoracic aorta. CSF was obtained by cisternal puncture technique at the following time points; before stent-grafting, and 15, 30 and 60 min after stent-grafting. Parallel arterial blood samples were also obtained using a heparinized syringe. All samples were centrifuged and the supernatant analysed for lactate. RESULTS: The mean preprocedural lactate concentration in the CSF was 1.7+/-0.3 mmol/l. Mean postprocedural levels in the experimental group at 15, 30 and 60 min were 3.1+/-1.9, 3.9+/-1.1 and 11.9+/-2.5 mmol/l, respectively (control values; 2.1+/-1.9, 2.7+/-1.1 and 1.9+/-1.5 mmol/l, respectively). Mean preprocedural blood lactate level was 1.8+/-0.6 mmol/l, while the mean postprocedural concentrations in the experimental group at 15, 30 and 60 min were 2.9+/-1.2, 3.4+/-1.7 and 3.9+/-2.0 mmol/l, respectively. Two out of the five animals in the experimental group suffered mild to moderate hind limb weakness. CONCLUSION: Selective placement of stent-grafts against the ARM in dogs resulted in a conspicuous increase in CSF and blood lactate concentrations 60 min after the procedure with or without physical signs of neurological deficits. Although the small sample size of this preliminary study does not allow any definitive conclusion, it may be worthwhile to confirm the findings in appropriately controlled larger studies.
Descriptors: blood vessel prosthesis, blood vessel prosthesis implantation adverse effects, lactic acid metabolism, spinal cord ischemia etiology, stents, thoracic arteries surgery, aortography, biological markers metabolism, blood vessel prosthesis implantation instrumentation, dogs, lactic acid blood, lactic acid cerebrospinal fluid, models, animal, motor activity, pilot projects, prosthesis design, spinal cord ischemia metabolism, spinal cord ischemia physiopathology, thoracic arteries radiography, time factors, up regulation.

Basso, C., P.R. Fox, K.M. Meurs, J.A. Towbin, A.W. Spier, F. Calabrese, B.J. Maron, and G. Thiene (2004). Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease. Circulation 109(9): 1180-1185. ISSN: 1524-4539.
NAL Call Number: RC681.A1 C8
Abstract: BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. METHODS AND RESULTS: ARVC was diagnosed in 23 boxer dogs (12 male; 9.1+/-2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4+/-18.8% versus 13.8+/-3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6+/-19.2% versus 84.8+/-3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. CONCLUSIONS: We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.
Descriptors: boxer dog, genetically transmitted animal model, arrhythmogenic right ventricular cardiomyopathy (ARVC), morbidity risk, histopathological abnormalities.

Bauer, A., J.K. Donahue, F. Voss, R. Becker, P. Kraft, J.C. Senges, K. Kelemen, H.A. Katus, and W. Schoels (2004). Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long qt syndrome. Naunyn Schmiedeberg's Archives of Pharmacology 369(4): 447-454. ISSN: 0028-1298.
NAL Call Number: 448.8 AR2
Abstract: Increasing the heart rate is one option for suppressing bradycardia-dependent polymorphic ventricular tachycardias (PVTs). The mechanisms underlying preventive pacing in acquired forms of the long QT syndrome (LQTs) are still not fully understood. Using two needle electrodes, local effective refractory periods (ERPs) were determined in the left (LV) and right ventricle (RV) in 20 dogs with acute AV node ablation before continuous pacing, during a 20-min period of continuous fast pacing (Cl 300 ms, fastpac) and during a 35-min recovery period with slow (Cl 500 ms) pacing. This protocol was applied to control dogs (5 dogs) and dogs with pretreatment of the IKs blocking agent chromanol 293b (5 dogs, LQTs1), the IKr-blocking agent dofetilide (5 dogs, LQTs2) or a combination thereof (5 dogs). Fastpac resulted in a significant abbreviation of ERPs in control dogs and dogs receiving dofetilide or chromanol 293b. During recovery, shortening of ERPs persisted in the control group, but diminished in dogs with acquired LQTs. In dogs with LQTs2 fastpac could not suppress inhomogeneity of refractoriness during recovery. With pretreatment of dofetilide and chromanol 293b in combination, MAP duration during fastpac significantly increased (first beat: 256+/-6 ms vs. sixth beat: 278+/-9 ms, p<0.05) and fastpac-induced PVTs were evident. ERP shortening and reduced inhomogeneity of refractoriness might be one antiarrhythmic action of fastpac in dogs with acute AV-block. However, in the acquired LQTs1 and 2 beneficial effects of fastpac diminished and in a combination thereof fastpac-induced PVTs are likely.
Descriptors: cardiovascular system, transport and circulation, acquired long QT syndrome, heart disease, polymorphic ventricular tachycardia, heart disease, fast cardiac pacing, antiarrhythmic effects, proarrhythmic effects, heart rate.

Bayar, M.A., Y. Erdem, K. Ozturk, O. Bescalti, M. Caydere, D. Yucel, Z. Buharali, and H. Ustun (2003). The effect of egb-761 on morphologic vasospasm in canine basilar artery after subarachnoid hemorrhage. Journal of Cardiovascular Pharmacology 42(3): 395-402. ISSN: 0160-2446.
Abstract: This study investigated the effects of Ginkgo biloba extract (EGb-761), an anti-oxidant and platelet-activating factor antagonist, on basilar artery vasospasm in an experimental canine subarachnoid hemorrhage model. Morphometric analyses were performed, and serum and cerebrospinal fluid endothelin-1 levels were measured by radioimmunoassay. Comparisons were made between treated and untreated groups. Twenty-four mongrel dogs were randomly assigned to three groups. The animals in group 1 (n=8) were not subjected to subarachnoid hemorrhage and received no treatment. In this group, serum and cerebrospinal fluid endothelin-1 levels were measured daily for 8 days. On day 9, the animals were killed and their basilar arteries were excised for histopathological examination. In group 2 (n=8), subarachnoid hemorrhage was produced using autologous arterial blood, and daily intravenous boluses of saline were administered for the next 8 days. Assessments of endothelin-1 levels and the basilar arteries were performed as described for group 1. In group 3 (n=8), subarachnoid hemorrhage was produced using autologous arterial blood, and daily intravenous boluses of EGb-761 were administered for 8 days. Endothelin-1 levels and the basilar arteries were assessed as described above. The groups' serum endothelin-1, cerebrospinal fluid endothelin-1, and histopathological findings were compared. In group 1, the serum and cerebrospinal fluid endothelin-1 levels did not change significantly over the 8 days, and histopathological examination of the basilar arteries revealed no abnormalities. In group 2, the serum and cerebrospinal fluid endothelin-1 levels increased abruptly and significantly on day 2, and remained high to the end of the study period (day 8). Histopathological examination revealed marked vasospasm. In group 3, the serum and cerebrospinal fluid endothelin-1 levels followed the same pattern observed in group 2; however, the arteries showed significantly less vasospasm than that observed in group 2. The study findings did not provide information about the mechanism of action of the platelet-activating factor-antagonist EGb-761, but they clearly show that this agent decreases morphologic vasospasm in the dog basilar artery.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacognosy, pharmacology, cerebral vasospasm, nervous system disease, vascular disease, subarachnoid hemorrhage.

Behringer, W., P. Safar, X. Wu, R. Kentner, A. Radovsky, P.M. Kochanek, C.E. Dixon, and S.A. Tisherman (2003). Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia. Critical Care Medicine 31(5): 1523-31. ISSN: 0090-3493.
Abstract: OBJECTIVES: This study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60-120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest. DESIGN: Prospective experimental comparison of three arrest times, without randomization. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (17-25 kg). INTERVENTIONS: Dogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2 degrees C (at a rate of 1 L/min), until tympanic temperature reached 20 degrees C (for 60 mins of cardiac arrest), 15 degrees C (for 60 mins of cardiac arrest), or 10 degrees C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. MEASUREMENTS AND MAIN RESULTS: We assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0-40, mild; 40-100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20 degrees C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15 degrees C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10 degrees C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10 degrees C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0-37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10 degrees C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22. CONCLUSIONS: In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10 degrees C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest-which rarely can be resuscitated effectively with current methods-can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.
Descriptors: animal model, cardiac arrest, brain damage, organ damage, resuscitation.

Bhattacharyya, M.L., K.P. Mull, Q. Debnam, S. Kabir, and A. Ivy (2003). Contrasting roles of a novel k+ channel blocker and a k+ channel opener on electro-mechanical activity in canine heart tissue. International Journal of Cardiology 89(1): 71-78. ISSN: 0167-5273.
Abstract: We tested the effects of a potassium channel opener diazoxide on the action potential duration (APD) and contractile force changes in canine Purkinje tissue induced by a novel class III anti-arrhythmic agent (C3A), KCB-328 (0.5 muM) with 3,4-dimethoxyphenethyl ring structure (0.5 muM). KCB-328 shortened APD25 by 8.3+-2.1%, prolonged APD50 and APD90 by 31.2+-5.3 and 50.0+-7.1%, respectively. Diazoxide (0.1 mM) shortened APD at all levels by 58.3+-8.1, 54.1+-6.1, and 42.8+-5.8%, respectively. In the presence of diazoxide, KCB-328 still prolonged APD50 and APD90 (12.5+-3.8 and 26.8+-5.9%, respectively). KCB-328 increased force of contraction in a dose-dependent manner. KCB-328 increased force less in the presence of diazoxide. Administration of diazoxide only, reduced force of contraction. We conclude that APD prolongation by KCB-328 may occur even in the presence of diazoxide. It is not sufficient for the restoration of already diminished contractile force and that such an APD prolongation may be unrelated to the restoration of force of contraction even though both are most often seen to occur simultaneously.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, action potential duration, prolongation.

Bin Jianping , K. Wei, and R.A. Pelberg (2000). Dipyridamole stress myocardial contrast echocardiography in detection coronary stenosis: a chest closed dog trial. Zhongguo Chaosheng Yixue Zazhi 16(6): 409-412. ISSN: 1002-0101.
Abstract: Objective: To assess the accuracy of myocardial contrast echocardiography (MCE) in combination with dipyridamole stress in detecting non-flow-limited coronary stenoses at rest. Methods: MCE was performed by intravenous injection of microbubbles (MRX-115) and radiolabled microspheres to measure myocardial blood flow (MBF)in 17 chest closed dogs. Chronical instrumental coronary stenoses models were created by placing ameroid contrictors. Data were acquired in 7-10 post-operative days. Results: No perfusion defects were noted at baseline. However, perfusion defects were seen in abnormal beds (MBF reserve<3) during dipyridamole stress. The peak video intensity(VI)in the abnormal beds was lower (33+-13 ver 50+-12; P<0. 01)than in normal beds with dipyridamole. An excellent linear relation was noted between the peak VI ratio (0. 6+-0. 2, abnormal/normal) and that of MBF using dipyridamole (r = 0. 89, P< 0. 0001). Conclusion: MCF with dipyridamole may be clinically useful for the detection and quantification of coronary stenoses.
Descriptors: radiology, medical sciences, cardiovascular system, transport and circulation, coronary stenosis, vascular disease, diagnosis, non flow limited, ameroid constrictor placement, surgical method, dipyridamole stress myocardial contrast echocardiography, accuracy, diagnostic method, myocardial blood flow.
Language of Text: Chinese.

Boswood, A. and A. Murphy (2006). The effect of heart disease, heart failure and diuresis on selected laboratory and electrocardiographic parameters in dogs. Journal of Veterinary Cardiology 8(1): 1-9. ISSN: 1760-2734.
NAL Call Number: SF811
Abstract: Objectives: To evaluate the influence of heart disease and heart failure on 9 parameters: the serum sodium, potassium, chloride, creatinine and urea concentrations, heart rate, vaso-vagal tonus index (VVTI), red cell number and hematocrit. Background: Previous studies have demonstrated that heart disease, heart failure and their treatment are associated with changes in laboratory and electrocardiographic parameters. Animals, materials and methods: Data were retrieved from 92 client-owned dogs with naturally occurring heart disease. Dogs were classified according to the severity of their heart disease and or the presence of heart failure. The effects of heart disease, the progression into heart failure, the initiation of successful therapy and the administration of diuretics on these parameters were determined. Results: Worse heart failure was characterized by the following changes: a significant fall in serum sodium and chloride concentrations and VVTI, and a significant increase in the serum urea concentration and heart rate. The onset of heart failure was characterized by a fall in VVTI and chloride concentration. The successful treatment of heart failure was characterized by a fall in heart rate, an increase in creatinine and sodium concentrations. Dogs receiving diuretics had higher heart rates, lower VVTI, higher urea concentrations, lower potassium, sodium and chloride concentrations. Conclusions: Numerous complex alterations in some of the studied parameters are associated with heart disease, heart failure and their treatment. Further consideration of these changes may improve our skills in diagnosis, prognostication and treatment..
Descriptors: blood composition, creatinine, diagnosis, diuresis, electrocardiography , haematocrit, heart, heart diseases, heart rate, medical treatment, potassium, potassium chloride, sodium, urea.

Briot, R., S. Bayat, D. Anglade, J.L. Martiel, and F.A. Grimbert (2003). Increased cardiac output induced by terbutaline may recruit injured capillaries during recovery from oleic acid lung injury. FASEB Journal 17(4-5): Abstract No. 562.10. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: terbutaline, a beta 2-agonist, cardiovascular system, transport and circulation, pharmacology, respiratory system, respiration, lung injury, injury, respiratory system disease, chemically induced, broncho alveolar lavage technique, laboratory techniques, capillary alveolar macromolecular permeability [camp], cardiac input, microvascular permeability.

Burashnikov, A. and C. Antzelevitch (2008). Can inhibition of IKur promote atrial fibrillation? Heart Rhythm the Official Journal of the Heart Rhythm Society 5(9): 1304-9.
Abstract: BACKGROUND: Block of ultrarapid delayed rectified potassium current (I(Kur)), present in atria but not in ventricles, is thought to be a promising approach for atrial-specific therapy of atrial fibrillation (AF). However, it has been shown that I(Kur) block may abbreviate atrial repolarization and that loss-of-function mutations in KCNA5, which encodes K(v) 1.5 channels responsible for I(Kur), is associated with familial AF. OBJECTIVE: Our objective in this study was to use low concentrations of 4-aminopyridine (4-AP, 10 to 50 microM), known to selectively block I(Kur), to assess the proarrhythmic and antiarrhythmic effects of I(Kur) block in healthy and remodeled atria. METHODS: Isolated canine coronary-perfused right atrial preparations were used. Acetylcholine or ischemia/reperfusion was used to acutely remodel the atria. Transmembrane action potentials and a pseudo-electrocardiogram were simultaneously recorded. RESULTS: Normal (healthy) atria typically displayed action potentials (AP) with a prominent plateau, whereas remodeled atria displayed triangular-shaped APs (remodeled). In healthy atria, in which AF could not be induced with programmed stimulation, 4-AP abbreviated action potential measured at 90% repolarization (APD(90)) and effective refractory period (ERP), permitting the induction of AF in 4 of 12 preparations (33%). In remodeled atria, 4-AP produced little (50 microM) to no (10 to 25 microM) prolongation of APD(90) or ERP and was either ineffective or poorly effective in terminating AF or preventing its induction. CONCLUSION: Our findings suggest that block of I(Kur) can provide the substrate for development of AF in healthy canine atria, presumably via abbreviation of APD and ERP.
Descriptors: 4 aminopyridine pharmacology, atrial fibrillation drug therapy, heart atria innervation, potassium channel blockers pharmacology, potassium channels drug effects, action potentials drug effects, anti arrhythmia agents therapeutic use, atrial fibrillation physiopathology, delayed rectifier potassium channels drug effects, dogs, heart atria drug effects, heart atria physiopathology, models, animal, potassium channels, voltage gated drug effects, risk factors.

Cardinal, R., C. Bouchard, M. Vermeulen, and P. Page (2000). Creation of a monomorphic ventricular tachycardia substrate in a canine chronic preparation of stable myocardial hypoperfusion and tachycardia-induced energetic stress. Canadian Journal of Cardiology 16 (Supplement F): 186F. ISSN: 0828-282X.
Descriptors: biochemistry and molecular biophysics, membranes, cell biology, cardiovascular system, transport and circulation, energetic stress, monomorphic ventricular tachycardia, myocardial hypoperfusion, sodium ion current, meeting abstract.

Cesselli, D., I. Jakoniuk, L. Barlucchi, A.P. Beltrami, T.H. Hintze, B. Nadal Ginard, J. Kajstura, A. Leri, and P. Anversa (2001). Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circulation Research 89(3): 279-286. ISSN: 0009-7330.
NAL Call Number: RC681.A1A57137
Abstract: Cell death has been questioned as a mechanism of ventricular failure. In this report, we tested the hypothesis that apoptotic death of myocytes, endothelial cells, and fibroblasts is implicated in the development of the dilated myopathy induced by ventricular pacing. Accumulation of reactive oxygen products such as nitrotyrosine, potentiation of the oxidative stress response by p66shc expression, formation of p53 fragments, release of cytochrome c, and caspase activation were examined to establish whether these events were coupled with apoptotic cell death in the paced dog heart. Myocyte, endothelial cell, and fibroblast apoptosis was detected before indices of severe impairment of cardiac function became apparent. Cell death increased with the duration of pacing, and myocyte death exceeded endothelial cell and fibroblast death throughout. Nitrotyrosine formation and p66shc levels progressively increased with pacing and were associated with cell apoptosis. Similarly, p50 (DELTAN) fragments augmented paralleling the degree of cell death in the failing heart. Moreover, cytochrome c release and activation of caspase-9 and -3 increased from 1 to 4 weeks of pacing. In conclusion, cardiac cell death precedes ventricular decompensation and correlates with the time-dependent deterioration of function in this model. Oxidative stress may be critical for activation of apoptosis in the overloaded heart.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, dilated cardiomyopathy, heart disease, heart failure, ventricular dysfunction, apoptosis, cell death, oxidative stress.

Cha, S.H., M.H. Han, Y.H. Choi, C.J. Yoon, S.K. Baik, S.J. Kim, and K.H. Chang (2003). Vascular responses in normal canine carotid arteries: comparison between various self-expanding stents of the same unconstrained size. Investigative Radiology 38(2): 95-101. ISSN: 0020-9996.
Abstract: RATIONALE AND OBJECTIVES: To compare long-term vascular responses upon the insertion of various self-expandable stents, all the same unconstrained size, in canine carotid artery models. MATERIALS AND METHODS: Twenty-two stents (5 SMARTs, 5 Wallstents, 6 Niti-Ss, 6 Niti-Ds) of the same unconstrained size (6 mm in diameter, 20 mm in length) were endovascularly placed in canine common carotid arteries. The luminal changes were measured on three occasions, on prestenting, immediate poststenting, and angiograms taken before specimens were killed. After en-bloc harvest of the stented carotid arteries at 6 months, the intraluminal surface was evaluated by gross observation and scanning electron microscopy (SEM). Neointimal thickness was measured at several points both over the wire and between the wires. RESULTS: Niti-D was excluded from analysis because of high rate of poststenting occlusion. SMART stent showed the greatest expansibility with average initial luminal gain (P<0.05) of 21.2% (Niti-S: 16.5%, Wallstent: 12.9%). At 6 months follow-up, the dilated arterial lumen had returned almost to the prestenting caliber without any significant differences among the stent types (P>0.05). The thickness of neointimal coverage was more prominent with SMART stent (354 mum over the wire and 258 mum between the wires) than Niti-S (228 mum and 83 mum) or Wallstent (187 mum and 78 mum). CONCLUSION: Stent types with its higher initial luminal gain appeared to be associated with thicker neointimal formation at 6 months. The acute expanding force of a self-expanding stent may be the key to the cause of neointimal hyperplasia. Regardless of the inserted stent type, the variations in neointimal response were offset by luminal gains of varying degree, thus preserving the arterial patency almost to the prestenting size.
Descriptors: cardiovascular system, transport and circulation, equipment apparatus devices and instrumentation, neointimal hyperplasia, vascular disease, smart self expandable stent, medical equipment, wall stent, medical equipment, angiogram, clinical techniques, diagnostic techniques, scanning electron microscopy, imaging and microscopy techniques, laboratory techniques, stent size, stent type.

Chin, B.B., G. Esposito, and D.L. Kraitchman (2002). Myocardial contractile reserve and perfusion defect severity with rest and stress dobutamine 99mtc-sestamibi spect in canine stunning and subendocardial infarction. Journal of Nuclear Medicine 43(4): 540-550. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Abstract: Myocardial contractile reserve and resting perfusion scintigraphy provide independent information to assess myocardial viability. The purpose of this study was to simultaneously evaluate both with 99mTc-sestamibi SPECT and low-dose dobutamine in canine stunning and subendocardial infarction (SEMI). Methods: Eighteen dogs were included in the study: 7 normal, 7 stunned, and 4 with SEMI. Closed-chest stunning and SEMI were produced by angioplasty balloon occlusion of the left anterior descending artery (20 and 90 min, respectively). Subsequent radiolabeled mircospheres confirmed reflow, and 99mTc-sestamibi was then administered at rest. Gated SPECT and MRI tagging were performed at rest and during low-dose dobutamine infusion (5 mug/kg/min). SPECT systolic wall thickening index (SWI) and MRI radial strain quantified myocardial contraction. Postmortem 2,3,5-triphenyltetrazolium chloride staining quantified SEMI. Results: Defect severity by SPECT in the anterior wall was mild and was not statistically different for the stunned versus SEMI groups (P=not significant). At rest, anterior wall SPECT SWI was significantly higher in the normal versus stunned groups (21.1+-3.1 vs. 10.1+-9.0; P=0.0002) and the normal versus SEMI groups (21.1+-3.1 vs. 2.6+-6.0; P=0.000002). With low-dose dobutamine, SWI increased significantly compared with rest for the stunned group (29.1+-10.4 vs. 10.1+-9.0; P=0.000007) but did not increase significantly for the SEMI group (11.0+-11.3 vs. 2.6+-6.0; P=0.09); SWI during low-dose dobutamine infusion for the stunned group was comparable to that for the normal group (29.1+-10.4 vs. 28.2+-7.0; P=0.80). SWI also showed correlation with MRI radial strain (r=0.42; P=0.00015). Conclusion: Defect severity for stunned myocardium and SEMI was mild and was not significantly different. Contractile reserve was significantly different in stunned myocardium and SEMI. 99mTc-Sestamibi SPECT at rest and with low-dose dobutamine is a promising new technique to simultaneously assess myocardial perfusion and contractile reserve.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, radiation biology, myocardial infarction, heart disease, vascular disease, myocardial stunning, subendocardial infarction, heart disease, magnetic resonance imaging, imaging techniques, imaging method, technetium 99m sestamibi spect, technetium 99m sestamibi single photon emission computed tomography, imaging method, rest, stress.

Cho, S., S. Zhang, H. Ureshino, T. Hara, S. Tomiyasu, and K. Sumikawa (2003). Hemodynamic interactions of propofol and dantrolene in chronically instrumented dogs. Anesthesia and Analgesia 96(5): 1369-1373. ISSN: 0003-2999.
Abstract: The hemodynamic interaction of dantrolene, a specific drug for malignant hyperthermia, and propofol which appears to be safe in malignant hyperthermia-susceptible patients, has not been investigated. We performed this study to examine the hemodynamic actions of dantrolene at a therapeutic dose during propofol anesthesia. Ten dogs were chronically instrumented for the measurements of systemic and coronary hemodynamics. The dogs were assigned to receive propofol with vehicle or dantrolene in a random manner on separate experimental days. Propofol significantly decreased mean arterial blood pressure, left ventricular systolic and end-diastolic pressure, the maximal rate of increase in left ventricular pressure, and left ventricular regional segment shortening. Coronary blood flow (CBF) was unchanged but coronary vascular resistance (CVR) decreased. Dantrolene reversed the decrease in mean arterial blood pressure and left ventricular systolic pressure caused by propofol, and significantly increased heart rate. However, left ventricular end-diastolic pressure, cardiac output, maximal rate of increase in left ventricular pressure, and segment shortening were unchanged. CBF was significantly increased with a decrease in CVR. These results suggest that dantrolene reverses the hypotensive action produced by propofol and causes an increase in CBF with a decrease in CVR, but does not significantly change the negative inotropic effects. Thus, dantrolene exerts favorable hemodynamic effects during propofol anesthesia.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, malignant hyperthermia, metabolic disease, muscle disease, drug induced, cardiac output, coronary blood flow, drug drug interaction, mean arterial blood pressure.

Chou, C.C., B.L. Nguyen, A.Y. Tan, P.C. Chang, H.L. Lee, F.C. Lin, S.J. Yeh, M.C. Fishbein, S.F. Lin, D. Wu, M.S. Wen, and P.S. Chen (2008). Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure. Heart Rhythm the Official Journal of the Heart Rhythm Society 5(8): 1170-7.
Abstract: BACKGROUND: Heart failure increases autonomic nerve activities and changes intracellular calcium (Ca(i)) dynamics. OBJECTIVE: The purpose of this study was to investigate the hypothesis that abnormal Ca(i) dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS: Simultaneous optical mapping of Ca(i) and membrane potential was performed in isolated Langendorff-perfused PV-left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 micromol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS: Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Ca(i), late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 +/- 0.6 beats/s (N = 4) to 6.5 +/- 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV-LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid-Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION: Ca(i) dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.
Descriptors: acetylcholine pharmacology, calcium metabolism, heart failure physiopathology, heart ventricles drug effects, pulmonary veins drug effects, pulmonary veins physiopathology, vasodilator agents pharmacology, acetylcholine administration and dosage, calcium transporting atpases drug effects, cardiac pacing, artificial, dogs, enzyme inhibitors pharmacology, heart failure etiology, models, animal, ryanodine pharmacology, stroke volume, thapsigargin pharmacology, vasodilator agents administration and dosage, left ventricular function.

Christian, T.F., A.H. Aletras, and A.E. Arai (2008). Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: comparison to single-bolus injection method. Journal of Magnetic Resonance Imaging JMRI 27(6): 1271-7. ISSN: 1053-1807.
Abstract: PURPOSE: To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). MATERIALS AND METHODS: Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI). RESULTS: Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. CONCLUSION: Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results. 2008 Wiley-Liss, Inc
Descriptors: contrast media administration and dosage, coronary circulation physiology, gadolinium dtpa administration and dosage, image enhancement methods, magnetic resonance angiography methods, blood flow velocity, dogs, microspheres, models, animal, reproducibility of results, time factors.

Chu, Y., Y.C. Wu, Y.C. Chou, H.Y. Chueh, H.P. Liu, J.J. Chu, and P.J. Lin (2004). Endothelium-dependent relaxation of canine pulmonary artery after prolonged lung graft preservation in university of wisconsin solution: role of l-arginine supplementation. Journal of Heart and Lung Transplantation 23(5): 592-598. ISSN: 1053-2498.
Abstract: Background: The University of Wisconsin (UW) solution has been demonstrated to enhance pulmonary allograft preservation. Endothelial nitric oxide (NO) production has been shown to be significantly impaired after ischemia and reperfusion (I/R) injury. The present experiments aimed to determine the protective effects of pulmonary endothelium-dependent function by using supplemental NO in University of Wisconsin (UW) solution following prolonged lung graft preservation. Methods: Thirty-six healthy mongrel dogs underwent thoracotomy to expose the left lung. In addition to a group given UW solution (n = 4), 100 mumol/liter L-arginine, (n = 7), 100 mumol/liter NG-monomethyl-L-arginine (L-NMMA n = 7) and 1.0 mumol/liter 3-morpholinosydnonimine (SIN-1, n = 18 respectively, were added to UW solution, and infused from the aortic root and pulmonary artery to the pulmonary vein. The perfused lung was then allowed to inflate to its maximum volume for 24-hour oxygenated preservation in each supplemented condition of UW solution at 4degreeC. In the SIN-1 group, the preservation period was further divided into 8 hours and 16 hours, respectively. Rings of the third-order pulmonary artery of the inflated lung were then suspended in organ chambers to measure isometric force. Results: Endothelium-dependent relaxation (EDR) to acetylcholitie, adenosine diphosphate and sodium fluoride of the pulmonary rings in the L-arginine group was significantly preserved compared with UW-solution-only group. The L-NMMA group showed significant EDR impairment after 24-hour preservation compared with the UW solution group. Similar to the L-arginine group, the SIN-1 group showed significant EDR protection with 8-hour preservation, but not with 24-hour preservation. In contrast, EDR to calcium ionophore A23187 showed no EDR changes after 24-hour preservation in any of the supplemented groups. Conclusions: Supplemental L-arginine in UW solution ameliorates impaired pulmonary EDR following prolonged lung preservation of up to 24 hours.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, respiratory system, respiration, ischemia and reperfusion injury, vascular disease, pathology, prolonged lung graft preservation.

Coxson, P.G., K.M. Brennan, S.E. Taylor, M.K. Huesman, S. Lim, R.H. Huesman, and T.F. Budinger (1996). Dipyridamole-induced stress-variability in 82rb pet kinetic studies in the anesthetized canine. Journal of Nuclear Medicine 37(5 SUPPL.): 146P. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Descriptors: cardiovascular system, transport and circulation, morphology, meeting abstract, meeting poster, myocardium, rubidium 82 positron emission tomography.

Cremona, G., C.F. Donner, and T.S. Hakim (1997). Nonlinear behaviour of resistance and compliance in isolated dog lung lobes. European Respiratory Journal Supplement 10(25): 433S-434S. ISSN: 0904-1850.
Descriptors: cardiovascular system, transport and circulation, respiratory system, respiration, pulmonary hemodynamics, meeting abstract.

Ding, C., L. Rao, S.F. Nagueh, and D.S. Khoury (2005). Dynamic three-dimensional visualization of the left ventricle by intracardiac echo cardiography. Ultrasound in Medicine and Biology 31(1): 15-21. ISSN: 0301-5629.
NAL Call Number: QC244.U4
Descriptors: cardiovascular system, transport and circulation, methods and techniques, intracardiac echocardiography, laboratory techniques, hemodynamics, left ventricular volume, catheterization.

Discigil, B., R.M. King, P.J. Pearson, V.K. Capellini, A.J. Rodrigues, H.V. Schaff, and P.R. Evora (2008). High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries. Revista Brasileira De Cirurgia Cardiovascular Orgao Oficial Da Sociedade Brasileira De Cirurgia Cardiovascular 23(2): 190-6.
Abstract: OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M), Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.
Descriptors: endothelium, vascular injuries, muscle, smooth, vascular injuries, nitric oxide biosynthesis, ultrasonic therapy adverse effects, ultrasonography, interventional adverse effects, acetylcholine pharmacology, adenosine diphosphate pharmacology, analysis of variance, coronary vessels injuries, coronary vessels metabolism, dogs, endarterectomy methods, endothelium, vascular drug effects, endothelium, vascular physiopathology, isoproterenol pharmacology, models, animal, muscle, smooth, vascular drug effects, muscle, smooth, vascular physiopathology, nitroprusside pharmacology, sodium fluoride pharmacology, ultrasonography, interventional methods, vasodilation drug effects, vasodilation physiology.
Language of Text: Portuguese.

Doi, A., M. Takagi, I. Toda, M. Teragaki, M. Yoshiyama, K. Takeuchi, and J. Yoshikawa (2003). Real time quantification of low temperature radiofrequency ablation lesion size using phased array intracardiac echocardiography in the canine model: comparison of two dimensional images with pathological lesion characteristics. Heart (London) 89(8): 923-927. ISSN: 1355-6037.
NAL Call Number: RB37.C43
Abstract: Objective: To evaluate the feasibility of quantifying low temperature radiofrequency catheter ablation (RFCA) lesions using a phased array intracardiac echocardiography (ICE) catheter-with better tissue penetration and in a deflectable device-in the canine model. Intervention: Low temperature radiofrequency (RF) energy (50-60degreeC at up to 40 W) was delivered to the left ventricle in 11 beagles for 60 seconds, using an 8 French catheter with a deflectable tip and a 4 mm distal electrode. Main outcome measures: Comparison of the width and depth of RFCA lesions measured by ICE with pathological findings. Results: 33 RF energies were delivered in 11 dogs. 31 lesions (94%) were confirmed at necropsy. 27 of 31 ablation lesions (87%) were detected by ICE. The mean (SD) width and depth of the ICE detected lesions were 10.4 (2.6) mm and 5.7 (1.9) mm, respectively. Pathological findings showed that RFCA lesions consisted of inner and outer layers. Macroscopically, the mean (SD) width and depth of the inner layers were 7.6 (2.3) mm and 3.6 (1.2) mm and those for the whole layers were 10.0 (2.8) mm and 5.3 (1.5) mm, respectively. Microscopically, the inner and outer layers corresponded to necrotic and oedematous areas, respectively. The ICE detected lesion size had better correlation with the pathological measurements of the whole layers in width (r = 0.911) and in depth (r = 0.756). Conclusion: The real time evaluation of RFCA lesion size using the phased array ICE is feasible, even with a low temperature RF application. However, ICE slightly overestimates RFCA lesion size compared with pathological necrotic lesion size.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, french catheter, medical equipment, intracardiac echocardiography, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, radiofrequency catheter ablation, therapeutic and prophylactic techniques, lesion size, tissue penetration.

Dourado, P.M., J.M. Tsutsui, A.C.P. Chagas, W.J. Mathias, J.L. Andrade, and P.L. Da Luz (2003). The real value of contrast echocardiography in the identification of stunned myocardium in an occlusion-reperfusion dog model. FASEB Journal 17(4-5): Abstract No. 342.10. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, methods and techniques, muscular system, movement and support, veterinary medicine, medical sciences, ischemia, vascular disease, occlusion reperfusion, anterior descending coronary artery occlusion, experimental surgical techniques, laboratory techniques, contrast echocardiography, clinical techniques, diagnostic techniques, electromagnetic flowmeter, medical equipment, real time myocardial contrast echocardiography, diagnostic techniques, reperfusion, clinical techniques, therapeutic and prophylactic techniques, triphenyltetrazolium chloride staining, tcc, imaging and microscopy techniques, necrosis.

Eldstrom, J., D.R. Van Wagoner, and D. Fedida (2004). Kv1.5 Is highly expressed in canine atrial myocytes. Biophysical Journal 86(1): 533A. ISSN: 0006-3495.
NAL Call Number: 442.8 B5238
Abstract: Canine atria have been used as a model to study atrial fibrillation and the effects of rapid atrial pacing on atrial electrical remodeling. To date, Kv3.1 is thought to be the sole molecular species underlying the atrial-specific, ultra-rapid delayed rectifier K+ current (IKur) in canine atria. Here, using RT-PCR, we have found that Kv1.5 mRNA was highly expressed in canine atrial tissue, while message for Kv3.1 was not. Western analysis detected Kv3.1 only in brain preparations, while Kv1.5 was expressed at high levels in both atrial and ventricular membrane fractions. Confocal imaging clearly demonstrated the presence of Kv1.5 immunostaining in single atrial myocytes. The channel was found at the surface of the myocytes both at intercalated discs and along lateral membranes. Double labeling with a sarcomeric actinin antibody showed co-localization of the channel and actinin proteins where the Z-line met the surface membrane, supporting previous data from rat showing Kv1.5 can be immunoprecipitated with actinin-2. Kv3.1 staining was faintly observable but unchanged after pre-incubation of the antibody with the blocking peptide. We conclude from our results that Kv1.5 but not Kv3.1 is expressed in our canine atrial samples.
Descriptors: cardiovascular system, transport and circulation, membranes, cell biology, atrial fibrillation, heart disease, reverse transcriptase polymerase chain reaction, genetic techniques, laboratory techniques, atrial electrical remodeling, atrial specific ultra rapid delayed rectifier potassium ion current, rapid atrial pacing.

Eto, M., S. Morita, M. Sugiura, T. Yoshimura, R. Tominaga, and T. Matsuda (2007). Elastomeric surgical sealant for hemostasis of cardiovascular anastomosis under full heparinization. European Journal of Cardio Thoracic Surgery Official Journal of the European Association for Cardio Thoracic Surgery 32(5): 730-4. ISSN: 1010-7940.
NAL Call Number: RD598
Abstract: PURPOSE: We developed a novel surgical sealant, a viscous diisocyanated prepolymer, applicable to arterial hemostasis. The purpose of this study is to evaluate hemostatic effect of this surgical sealant under heparinized conditions. METHODS: The effectiveness of this sealant was verified by applying it to the end-to-end anastomosis of canine carotid arteries. Five mongrel dogs were used. After a complete heparinization, the carotid arteries were clamped, divided, and end-to-end anastomoses were performed with four simple interrupted sutures. The sealant was coated on the anastomosis. After 5 min the clamps were removed and the hemostatic effect was evaluated. Three dogs were immediately subjected to macroscopic evaluation. Two dogs were subjected to angiography after 3 months and 16 months, respectively. RESULTS: No bleeding occurred in any of the anastomoses immediately after the removal of the clamp. Macroscopic finding revealed no leakage of the sealant into the lumen. Carotid angiography revealed patent anastomoses without stenosis. CONCLUSION: A novel surgical sealant exhibited rapid and potent hemostatic effect on a moisturized tissue under full heparinization.
Descriptors: blood loss, surgical prevention and control, cardiovascular surgical procedures methods, hemostasis, surgical methods, polymers standards, tissue adhesives standards, anastomosis, surgical methods, dogs, hemorrhage prevention and control, models, animal, postoperative hemorrhage prevention and control.

Eto, Y., H. Yamada, Y. Zhang, D.A. Agler, E. Donal, and T.N. Mazgalev (2003). Effect of ventricular slowing during atrial fibrillation on relationship between cycle length irregularity and mitral annular velocity: a chronic conscious canine model. Circulation 108(17 Supplement): IV-393. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, methods and techniques, atrial fibrillation, heart disease, atrioventricular node vagal stimulation, clinical techniques, therapeutic and prophylactic techniques, right atrial pacing, clinical techniques, tissue doppler echocardiography, diagnostic techniques, r r interval, aortic pulse pressure, arterial pressure, cycle length irregularity, left ventricular ejection fraction, left ventricular systolic function, mitral annular systolic velocity, ventricular rate, ventricular slowing.

Eun, L.Y., E. Arruda, G.J. Ensing, and A. Ludomirsky (2003). Does cardiac muscle restoration of the left ventricle differ from the right ventricle in the normal canine heart? A passive stress-strain relationship. Pediatric Research 53(4 Part 2): 31A-32A ISSN: 0031-3998.
NAL Call Number: RJ1.P4
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, cardiac restoration, clinical techniques, therapeutic and prophylactic techniques, circumferential orientation, force length relationships, longitudinal orientation, passive stress strain relationship, lagrangian, radial orientation, ventricular diastolic function.

Fedorov, V.V., G.G. Beloshapko, A.V. Yushmanova, O.F. Sharifov, and L.V. Rosenshtraukh (2003). Effects of a new class iii antiarrhythmic drug nibentan in a canine model of spontaneous atrial fibrillation. European Heart Journal 24(Abstract Supplement): 391. ISSN: 0195-668X.
Descriptors: cardiovascular system, transport and circulation, pharmacology, atrial premature depolarization, heart disease, prevention and control, reentrant arrhythmia, heart disease, prevention and control, spontaneous atrial fibrillation, heart disease, drug therapy, atrial electrical stimulation, clinical techniques, ik potassium current, atrial effective refractory period, basic cycle length, conduction velocity.

Fedorov, V.V., O.P. Trifonova, A.V. Glukhov, G.G. Beloshapko, A.V. Iushmanova, and L.V. Rozenshtraukh (2004). Vliianie vnutripredserdnogo davleniia na kharakter vozniknoveniia vagotonicheskoi fibrilliatsii predserdii u sobak. Kardiologiia 44(12): 51-63. ISSN: 0022-9040.
Abstract: Atrial fibrillation (AF) frequently occurred under conditions associated with atrial dilatation (stretch) or vagal hyperactivity. To study possible role of atrial stretch in spontaneous initiation of vagal AF we compared changes of right atrial pressure (RAP) and activation patterns during AF beginning. In anesthetized open-chest dogs (n=45) AF was induced by stimulation of vagal nerves (VS) (30-60 Hz, 5-10 s train). VS resulted in sinus node arrest (4.7+/-0.7 sec) with subsequent AF initiation in 153 of 229 cases. In 41% of cases of AF initiation the first atrial wave (A(1)) was closely related to ventricular activation (V) with V-A(1) interval of 94+/-5 ms (<<ventricle-dependent>> AF). This ventricular excitation induced acute short increase of RAP from 6.6.+/-0.6 to 12.9+/-1.1 mmHg (p<0.00l). Whereas other cases of AF initiation (59%) had no relation to ventricular activation (A(1)-V interval of 1382+/-173 ms) (<<ventricle-independent>> AF). Atrial activation mapping (224 unipolar electrodes) showed that interval A(1)-A(2) of <<ventricle-dependent>> AF was significantly shorter than of <<ventricle-independent>>. These data indicate that atrial stretch induced by elevation of RAP may facilitate the induction of AF but do not play a significant role in the mechanism of spontaneous AF initiation in this animal model.
Descriptors: animal model, open chest dogs, atrial fibrillation, vagal hyperactivity, atrial stretch.
Language of Text: Russian

Fenelon, G., R.K. Shepard, and B.S. Stambler (2003). Focal origin of atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. Journal of Cardiovascular Electrophysiology 14(10): 1093-1102. ISSN: 1045-3873.
Abstract: Introduction: Dogs with rapid ventricular pacing-induced congestive heart failure (CHF) have inducible atrial tachycardia (AT), with a mechanism consistent with delayed afterdepolarization-mediated triggered activity. We assessed the hypothesis that AT has a focal origin. Methods and Results: Twenty-one CHF dogs undergoing 3 to 4 weeks of ventricular pacing at 235 beats/min were studied. Biatrial epicardial mapping of 20 sustained AT episodes (cycle length (CL), 175+-53 msec) in 5 dogs revealed an area of earliest activation in the right atrial (RA) free wall (13 episodes), RA appendage (4 episodes), or between the pulmonary veins (3 episodes). Total epicardial activation time during AT (73+-19 msec) was similar to that during sinus rhythm (72+-13 msec) and on average was <50% of the AT CL. Higher-density mapping of the RA free wall during 30 sustained AT episodes (163+-55 msec) in 9 dogs identified a site of earliest activation along the sulcus terminalis most frequently as a stable, focal activation pattern from a single site. Endocardial mapping of 49 sustained AT episodes (156+-27 msec) in 10 dogs revealed multiple sites of AT origin arising along the crista terminalis and pulmonary veins. Right and left ATs were terminated with discrete radiofrequency ablation, but other ATs remained inducible. A rapid, left AT generating an ECG pattern of atrial fibrillation was ablated inside the pulmonary vein. Conclusion: AT induced in this CHF model after 3 to 4 weeks of rapid ventricular pacing has an activation pattern consistent with a focal origin. Sites of earliest activation are distributed predominately along the crista terminalis and within or near the pulmonary veins.
Descriptors: cardiovascular system, transport and circulation, veterinary medicine, medical sciences, atrial tachycardia, heart disease, congestive heart failure, rapid ventricular pacing, induced heart failure, heart disease, biatrial epicardial mapping, clinical techniques, ventricular pacing, clinical techniques, sinus rhythm.

Forrest, M.J., D. Bloomfield, R.J. Briscoe, P.N. Brown, A.M. Cumiskey, J. Ehrhart, J.C. Hershey, W.J. Keller, X. Ma, H.E. McPherson, E. Messina, L.B. Peterson, W. Sharif Rodriguez, P.K. Siegl, P.J. Sinclair, C.P. Sparrow, A.S. Stevenson, S.Y. Sun, C. Tsai, H. Vargas, M.3. Walker, S.H. West, V. White, and R.F. Woltmann (2008). Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. British Journal of Pharmacology 154(7): 1465-73. ISSN: 0007-1188.
NAL Call Number: 396.8 B77
Abstract: BACKGROUND AND PURPOSE: Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib. EXPERIMENTAL APPROACH: Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models. KEY RESULTS: Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats. CONCLUSIONS AND IMPLICATIONS: Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands.
Descriptors: blood pressure drug effects, cholesterol ester transfer proteins antagonists and inhibitors, oxazolidinones toxicity, quinolines toxicity, adrenal cortex cytology, adrenal cortex drug effects, aldosterone blood, anticholesteremic agents toxicity, corticosterone blood, dogs, drug evaluation, preclinical, macaca mulatta, mice, mice, inbred c57bl, models, animal, muscle, smooth, vascular drug effects, muscle, smooth, vascular metabolism, rats, rats, sprague dawley, species specificity.
Notes: Comment In: Br J Pharmacol. 2008 Aug;154(7):1379-81.

Freitas, C.F., R. Faro, D. Dragosavac, M. Clozel, G. De Nucci, and E. Antunes (2004). Role of endothelin-1 and thromboxane a2 in the pulmonary hypertension induced by heparin-protamine interaction in anesthetized dogs. Journal of Cardiovascular Pharmacology 43(1): 106-112. ISSN: 0160-2446.
Abstract: This study aimed to study the role of thromboxane A2 (TXA2) and endothelin-1 (ET-1) in the pulmonary hypertension induced by interaction of heparin-protamine in anesthetized dogs. The effect of inhaled nitric oxide (NO) was also investigated in this model. Dogs were anesthetized and instrumented for acquisition of mean arterial blood pressure, mean arterial pulmonary pressure (MPAP), and pulmonary pressure gradient (PPG). Cardiac index (CI), heart rate, and index of systemic vascular resistance were also obtained. Intravenous administration of heparin (500 IU/kg) 3 minutes before protamine (10 mg/kg) caused marked pulmonary hypertension, as evaluated by the increase in MPAP and PPG. This was accompanied by systemic hypotension, CI decrease, and tachycardia. Indomethacin (10 mg/kg), dazoxiben (10 mg/kg), or tezosentan (10-mg/kg bolus plus 10-mg/kg/h infusion) significantly reduced the increase in MPAP and PPG, but had no effect on the systemic hypotension. Similar results were obtained with inhaled NO (3 ppm). Plasma TXB2 levels were markedly elevated during the pulmonary hypertension, and this was abolished in indomethacin-treated dogs. Our study shows that interaction of heparin-protamine in anesthetized dogs lead to TXA2- and ET-1-mediated pulmonary hypertension. Drugs that interfere with the synthesis of these mediators as well as inhaled NO may be of beneficial value to control this disorder.
Descriptors: cardiovascular system, transport and circulation, pharmacology, pulmonary hypertension, vascular disease, tachycardia, heart disease, cardiac index, heart rate, heparin protamine interaction, mean arterial blood pressure, mean arterial pulmonary pressure, pulmonary pressure gradient, systemic vascular resistance index.

Fujii, Y., K. Orito, M. Muto, and Y. Wakao (2007). Modulation of the tissue reninangiotensin-aldosterone system in dogs with chronic mild regurgitation through the mitral valve. American Journal of Veterinary Research 68(10): 1045-50. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: OBJECTIVE: To investigate whether the tissue and plasma renin-angiotensin-aldosterone system (RAAS) is activated in dogs with mild regurgitation through the mitral valve and determine the contribution of chymase and angiotensin-converting enzyme (ACE) to the activation of the RAAS and potential production of angiotensin II during the chronic stage of mild mitral valve regurgitation. ANIMALS: 5 Beagles with experimentally induced mild mitral valve regurgitation and 6 clinically normal (control) Beagles. PROCEDURES: Tissue ACE and chymase-like activities and plasma RAAS were measured and the RAAS evaluated approximately 1,000 days after experimental induction of mitral valve regurgitation in the 5 dogs. RESULTS: Dogs with experimentally induced mitral valve regurgitation did not have clinical signs of the condition, although echocardiography revealed substantial eccentric hyper- trophy. On the basis of these findings, dogs with mitral valve regurgitation were classified as International Small Animal Cardiac Health Council class Ib. Plasma activity of renin and plasma concentrations of angiotensin I, angiotensin II, and aldosterone were not significantly different between dogs with mitral valve regurgitation and clinically normal dogs. Tissue ACE activity was significantly increased and chymase-like activity significantly decreased in dogs with mitral valve regurgitation, compared with values in clinically normal dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The tissue RAAS was modulated without changes in the plasma RAAS in dogs with mild mitral valve regurgitation during the chronic stage of the condition. An ACE-dependent pathway may be a major route for production of angiotensin II during this stage of the condition.
Descriptors: dog diseases physiopathology, mitral valve insufficiency veterinary, renin angiotensin system physiology, chronic disease, chymases metabolism, dog diseases enzymology, dogs, mitral valve insufficiency enzymology, mitral valve insufficiency physiopathology, models, animal, peptidyl dipeptidase a metabolism, reference values.

Gallegos, R.P., C. Swingen, N.J. Xu, X. Wang, R. Bianco, M. Jerosch Herold, and R.M. Bolman (2004). Infarct extent by mri corelates with peak serum troponin level in the canine model. Journal of Surgical Research 120(2): 266-271. ISSN: 0022-4804.
Descriptors: Serum Troponin I, biochemistry and molecular biophysics, cardiovascular system, diagnosis, myocardial infarction, heart disease, vascular disease, magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, blood immunoassay, bioassay techniques, coronary artery ligation, therapeutic and prophylactic techniques, electrocardiography, thoracotomy, infarct size.

Garrido, M.J., M.R. Williams, A. Kherani, D.W. Vigilance, D. Parish, H. Hermoni, Y. Naka, C.R.J. Smith, M.C. Oz, and M. Argenziano (2003). Linear ethanol jet injection for surgical treatment of atrial fibrillation: canine survival study. Journal of the American College of Cardiology 41(6 Supplement A): 92A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, atrial fibrillation, heart disease, therapy, beating ethanol linear jet injection, laboratory techniques, therapeutic and prophylactic techniques.

Ge Lei , Wei Meng , Yao Rui Ming , and Et Al (2003). Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor in a canine model of acute myocardial infarction. Zhonghua Xinxueguanbing Zazhi 31(6): 452-455. ISSN: 0253-3758.
Abstract: Objective: To evaluate the effects of intramyocardial administration of basic fibroblast growth factor (bFGF) on myocardial blood flow and angiogenesis in a canine acute myocardial infarction model. Methods: Myocardial infarction was induced in 17 dogs by ligation of the first, second diagonal branches of left anterior descending (LAD) and the first, second obtuse marginal branches of LCX. 200 mug of human recombinant bFGF in 0.2 ml of saline was injected into the infarct border zone 20 minutes after coronary occlusion in 9 dogs, whereas 200 mul saline was used in 8 control dogs. Myocardial blood flow, which was expressed as percentage of normal, was determined with non-radioactive colored microspheres before and immediately after coronary ligation, 3 hours, 7 days and 28 days after treatment. Angiogenesis was determined at the end of the whole study. Results: Compared with control group, treatment with 200 mug bFGF significantly increased the epicardial blood flow in the infracted zone ((36.40+-2.04)% vs (32.32+-3.07)% 3 hours after coronary ligation, P<0.05; (56.30+-3.49)% vs (35.68+-1.62)% 7 days after coronary ligation, P<0.01; and (70.62+-3.17)% vs (46.20+-2.58)% 28 days after coronary ligation, P<0.01, respectively). bFGF also significantly increased the epicardial blood flow in the border zone ((68.06+-2.69)% vs (53.94+-2.27)% 7 days after coronary ligation, P<0.01; (79.74+-4.61)% vs (61.84+-4.52)% 28 days after coronary ligation, P<0.01, respectively). bFGF increased the vessel density in the infarcted zone (7.24+-1.89 vessels/mm2 vs 4.07+-1.89 vessels/mm2, P<0.05) and infarcted border zone (14.48+-4.69 vessels/mm2 vs 8.15+-3.43 vessels/mm2, P<0.05). Conclusion: The current study shows that intramyocardial administration of bFGF increases the regional myocardial blood flow and promotes myocardial collateral vessel formation in the canine acute myocardial infarction model.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, acute myocardial infarction, heart disease, vascular disease, coronary occlusion, coronary ligation, experimental surgical techniques, laboratory techniques, therapeutic angiogenesis, clinical techniques, therapeutic and prophylactic techniques.
Language of Text: Chinese.

Ge, Z.D., J. Moore, G.J. Gross, and J.A. Auchampach (2003). The a3 adenosine receptor agonist ib-meca reduces myocardial infarct size in anesthetized dogs. FASEB Journal 17(4-5): Abstract No. 151.5. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, myocardial infarction, heart disease, vascular disease, left anterior descending artery occlusion, experimental surgical techniques, laboratory techniques, coronary blood flow.

Ghiassi, S., Y.S. Sun, V.B. Kim, C.M. Scott, L.W. Nifong, M.F. Rotondo, and W.R.J. Chitwood (2004). Methylene blue enhancement of resuscitation after refractory hemorrhagic shock. Journal of Trauma Injury Infection and Critical Care 57(3): 515-521. ISSN: 1079-6061.
Abstract: Background: Methylene blue has been used to treat hypovolemic states. This study evaluated prehospital resuscitation after refractory hemorrhagic shock with a combination of methylene blue and limited-volume lactated Ringer's solution. Methods: After blood loss to a mean arterial pressure of 50 mm Hg in canines, refractory hemorrhagic shock was defined as minimal hemodynamic response to phenylephrine. Differential protocols included no treatment (control), methylene blue bolus, limited-volume lactated Ringer's solution, and combined methylene blue/lactated Ringer's solution therapies. Hemodynamic parameters were collected at baseline, during shock, during refractory hemorrhagic shock, and 30, 60, 90, and 120 minutes after treatment. Radiolabeled microspheres were used to measure end-organ perfusion and oxygen delivery. Results: Methylene blue/lactated Ringer's resuscitation improved prehospital survival (p 0.05), mean arterial pressure and cardiac output (p 0.05), vital end-organ blood flow and oxygen delivery (p 0.05), and decreased serum lactate levels (p 0.05), as compared with the methylene blue and lactated Ringer's single therapies. Conclusions: Resuscitation after refractory hemorrhagic shock using a combination of methylene blue and limited-volume lactated Ringer's solution improves prehospital survival and hemodynamic stability and reduces ischemic damage in an acute setting. This form of therapy has been proved useful as a temporizing measure for resuscitation after refractory hemorrhagic shock in a canine model and warrants further study for its application to the hemorrhagic trauma patient.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, nervous system, neural coordination, hemorrhagic shock, nervous system disease, vascular disease, radiolabeling, laboratory techniques, arterial pressure, cardiac output, end organ blood flow.

Glaus, T.M., M. Hassig, C. Baumgartner, and C.E. Reusch (2003). Pulmonary hypertension induced in dogs by hypoxia at different high-altitude levels. Veterinary Research Communications 27(8): 661-670. ISSN: 0165-7380.
NAL Call Number: SF601 .V38
Abstract: Chronic natural hypoxia at 2300 in altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 in (PaO2 52+-5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 in (48%+-4%) did not differ from that at 2300 in (49%+-40%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105+-13 mmHg at 3500 m versus 98+-17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR Vmax was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 in (33.6-54.8 mmHg), when PH was defined as TR Vmax gtoreq2.8 m/s, i.e. a peak pressure gradient >30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period.
Descriptors: blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, erythrocytosis, polycythemia, pulmonary hypertension, vascular disease, tricuspid regurgitation, heart disease, blood pressure, chronic natural hypoxia, high altitude, packed cell volume.

Grover, G.J., D.E. Burkett, C.S. Parham, R.J. Scalese, and K.K. Sadanaga (2003). Protective effect of mitochondrial katp activation in an isolated gracilis model of ischemia and reperfusion in dogs. Journal of Cardiovascular Pharmacology 42(6): 790-792. ISSN: 0160-2446.
Abstract: Adenosine triphosphate-sensitive potassium channel (KATP) openers protect ischemic myocardium by direct protection of cardiac myocytes, which is thought to be a result of activation of mitochondrial KATP (mKATP). KATP is expressed in skeletal muscle, and the purpose of this study was to determine the effect of the mKATP opener BMS-191095 on infarct size in an isolated gracilis model of ischemia and reperfusion in dogs. The right and left gracilis muscles were isolated in anesthetized dogs except for the artery and vein supplying these muscles (pedicle). BMS-191095 (0.4 mg) or vehicle were infused directly into the artery supplying each gracilis muscle (each animal had one drug-treated and one vehicle-treated muscle). The pedicle was completely occluded for 5 hours followed by 48 hours of reperfusion, after which infarct size was determined. In the vehicle-treated gracilis muscles, significant necrosis was observed (82%+-3% of gracilis muscle). BMS-191095 significantly reduced the infarct size in the contralateral gracilis muscle (55%+-6%). Reflow into the gracilis muscle was significantly greater in BMS-191095-treated muscles. BMS-191095 appears to reduce damage in ischemic/reperfused skeletal muscle, suggesting that mKATP activation is an important protective mechanism in this tissue.
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, pharmacology, ischemia, vascular disease, ischemia reperfusion injury, myocardial ischemia, heart disease, infarct size, isolated gracilis model.

Grundfest, W.S., J. Val Mejias, E. Monnet, B.P. Knight, S. Nazarian, R.D. Berger, T.B.J. Ferguson, M.M. Roden, D. Amundson, J. Hanlin, and L. Blankenship (2007). Real-time percutaneous optical imaging of anatomical structures in the heart through blood using a catheter-based infrared imaging system. Seminars in Thoracic and Cardiovascular Surgery 19(4): 336-41. ISSN: 1043-0679.
Abstract: The ability to optically image structures and instrumentation within the heart during procedures is limited by the presence of blood in the field. The goal of our research was to design, develop, and evaluate technology for a catheter-based optical imaging system that enables intracardiac and intravascular visualization in real time through blood. Based on Mie optical scattering theory, imaging through blood using infrared light was theoretically feasible, but scattering in the near-infrared wavelengths (1100 to 1300 nm) generated substantial noise in the image despite relatively low absorption. Using illumination between 1550 and 1650 nm provided better images, as the effect of scattering is less while the effect of absorption is greater. Absorption losses can be overcome by increasing light intensity. Infrared (IR) transmitting endoscopes were constructed using novel flexible illumination and imaging bundles. Endoscope designs, all 7.5 Fr. in outer diameter, were used to obtain images of the coronary sinus, tricuspid valve, and great vessels in 25 pigs, 16 dogs, 1 calf, and 1 sheep. Imaging was successful in all 43 animals, but the coronary sinus was not always visualizable. After obtaining FDA 510(k) approval, the device was used to acquire images in 50 patients during placement of electrophysiologic leads via right heart catheterization. Clinical experience demonstrates successful visualization in the heart in 45 patients, although coronary sinus images were obtained only in 39 patients. High heart rates, large dilated hearts, and problems with catheter design prevented visualization in all patients. On occasion, it was possible to visualize the tricuspid valve. Infrared endoscopy allows for visualization of intimal surfaces of blood vessels, cardiac chambers, and valves through flowing blood. While technical challenges remain, the feasibility of the approach has been demonstrated.
Descriptors: angioscopy methods, heart anatomy and histology, heart catheterization instrumentation, infrared rays, optics and photonics, cattle, diagnostic imaging, dogs, feasibility studies, heart physiopathology, heart catheterization methods, models, animal, sheep, swine, time factors.

Gu, W., D. Weihrauch, K. Tanaka, J.P. Tessmer, P.S. Pagel, J.R. Kersten, W.M. Chilian, and D.C. Warltier (2003). Reactive oxygen species are critical mediators of coronary collateral development in a canine model. American Journal of Physiology 285(4 Part 2): H1582-H1589. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n=8) or presence of N-acetylcysteine (NAC) (occlusion+NAC, n=8). A sham group (n=8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71+-7%) in occlusion dogs after 21 days but remained unchanged (13+-3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28+-8%). Brief coronary artery occlusion and reperfusion caused ROS production (256+-33% of baseline values), which was abolished with NAC (104+-12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation.
Descriptors: cardiovascular system, transport and circulation, coronary artery occlusion, heart disease, vascular disease, coronary collateral blood flow.

Guan, D.W., X.G. Zhang, R. Zhao, B. Lu, Y. Han, Z.H. Hou, and J.T. Jia (2007). Diverse morphological lesions and serious arrhythmias with hemodynamic insults occur in the early myocardial contusion due to blunt impact in dogs. Forensic Science International 166(1): 49-57. ISSN: 0379-0738.
NAL Call Number: RA1001
Abstract: To investigate the morphology and hemodynamics of the early myocardial contusion, an animal model of cardiac contusion was established by impact to the precordial region at sternum at velocity of 10.0m/s with a mechanical elastic-cord propelled impactor in 19 dogs. The electrocardiogram and both the left and right intra-ventricular pressures were recorded continuously throughout the experiment. Histological and immunohistochemical examinations of myoglobin, creatine kinase-MB and fibrinogen were conducted. At the moment of impact, abrupt over-pressures within the left and right ventricles occurred with concomitant serious arrhythmias followed by variety of cardiac conduction disorders and depressed left and right ventricular systolic pressures during the observation times. Histologically, lesions of myocardial contusions were identified at subepicardial, myocardial or subendocardial layer as interstitial hemorrhage, disruption or coagulative necrosis as well as contraction band necrosis of the muscle fibers, which might be categorized into the hemorrhagic, necrotized and mixed forms. The three forms of lesions were found to exist independently, or co-existed in a heart. However, severity of the lesions varied greatly with different parts even within a heart. Intravascular thromboses were occasionally discovered post-impact. Immunohistochemically, loss of myoglobin and creatine kinase-MB from cardiac cells, and accumulation of fibrinogen at the cell membranes were detected 5min post-impact. The intracellular accumulation of fibrinogen increased with extension of post-impact intervals. Our results indicate that diverse morphological lesions concomitant with hemodynamic compromise and serious, even fatal arrhythmias occur in the early myocardial contusion, and intravascular thromboses are occasionally produced, suggesting that traumatic myocardial ischemic lesion may be induced due to blunt impact to the precordial region.
Descriptors: arrhythmias, cardiac physiopathology, heart injuries pathology, wounds, nonpenetrating pathology, dogs, electrocardiography, heart injuries physiopathology, immunohistochemistry, models, animal, ventricular pressure, wounds, nonpenetrating physiopathology.

Guccione, J.M., K.D. Costa, and A.D. Mcculloch (1995). Finite element stress analysis of left ventricular mechanics in the beating dog heart. Journal of Biomechanics 28(10): 1167-1177. ISSN: 0021-9290.
NAL Call Number: TA166.J6
Abstract: A three-dimensional finite element model was used to explore whether or not transmural distributions of end-diastolic and end-systolic fiber stress are uniform from the apex to the base of the canine left ventricular wall. An elastance model for active fiber stress was incorporated in an axisymmetric model that accurately represented the geometry and fiber angle distribution of the anterior free wall. The nonlinear constitutive equation for the resting myocardium was transversely isotropic with respect to the 4.6 kPa at the apex, and 3.3 kPa at the base. Transmural fiber stress differences at end-systole (14 kPa) were relatively small in regions from the base to the midventricle (13-22 kPa), but were larger between within or very close to one standard deviation of published measurements through the midanterior left ventricular free wall of the passive canine heart (Omens et al., Am. J. Physiol. 261, H918-H928 (1991)). End-systolic in-plane normal and shear strains also agreed closely with published experimental measurements in the beating dog heart (Waldman et al., Circ. Res. 63, 550-562 (1988)). The results indicate that, unlike in the midventricle region that has been studied most fully, there may be significant regional nonhomogeneity of fiber stress in the normal left ventricle associated with regional variations in shape and fiber angle.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, mathematical biology, computational biology, models and simulations, mathematical model, myocardium, myofiber stress, systole.

Guo Zhi Bin , Li Qing , Cao Hong Yu , and Xu Zhi (2003). Comparative study of propafenone and procainamide on canine ischemic ventricular tachyarrhythmias. Zhongguo Yaolixue Yu Dulixue Zazhi 17(5): 360-365. ISSN: 1000-3002.
Abstract: AIM: To observe the electrophysiologic effects of propafenone (Prop) on canine ischemic ventricular tachyarrhythmias and compared with those of procainamide (PA), so as to evaluate the effect and mechanism of Prop on ischemic ventricular tachyarrhythmias. METHODS: A canine ischemic ventricular tachyarrhythmia model was established by the left anterior descending coronary artery occlusion for 2 h and reperfusion. Five to eight days later, open-chest dogs were given programmed electrical stimulation (PES), and electrophysiologic data were measured by electrocardiogram (ECG). RESULTS: Both Prop and PA distinctly lengthened the QTc interval (P<0.01) and effective refractory period (ERP) of normal and ischemic ventricular myocardium respectively (P<0.01), decreased the dispersion of ERP in ischemic myocardium and in left ventricle (P<0.01), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably (P<0.01). Prop and PA effectively prevented PES- or ischemia-induced ventricular tachycardia or ventricular fibrillation (P<0.05, or P<0.01). CONCLUSION: The canine model is a worthy and reliable one. Prop and PA may be effective in preventing the onset of ventricular tachycardia or ventricular fibrillation after myocardial ischemic damage. The antiarrhythmic effects of both drugs are similar.
Descriptors: cardiovascular system, transport and circulation, pharmacology, ischemic ventricular tachyarrhythmia, heart disease, myocardial infarction, heart disease, vascular disease, ventricular fibrillation, ventricular tachycardia, electrocardiography, clinical techniques, diagnostic techniques, programmed electrical stimulation, experimental surgical techniques, laboratory techniques, qtc interval, comparative study, diastolic excitability threshold, disease onset, disease prevention, effective refractory period, electrophysiologic data.

Hainsworth, R., O.A. Sofola, A.J.P. Knill, and M.J. Drinkhill (2003). Influence of dietary salt intake on the response of isolated perfused mesenteric veins of the dog to vasoactive agents. American Journal of Hypertension 16(1): 6-10. ISSN: 0895-7061.
NAL Call Number: RC685.H8
Abstract: Background: Previous work has established that a high dietary salt intake results in enhanced arterial vasoconstrictor responses to stimulation with agonists. This investigation was designed to investigate the effects of dietary salt on the responses of isolated capacitance vessels (third order mesenteric veins). Methods: Dogs were fed diets containing low, intermediate, and high levels of dietary salt (0.4, 3.0, and 6.0 mmol kg/day). The animals were killed, and lengths of mesenteric vein were mounted in a perfusion myograph with changes in lumenal diameter measured using a video tracking device. Responses to cumulative doses of norepinephrine (NE) and acetylcholine (Ach) were then determined. Results: The vasoconstrictor responses to NE were greater in the veins from dogs on a high salt diet. Acetylcholine also caused venoconstriction that also was greater in the high salt group of animals. Responses to Ach were unaffected by Nomega-nitro-L-arginine methyl ester but were abolished by atropine. Conclusions: These results indicate that mesenteric veins from dogs fed a high salt diet constrict more powerfully in response to agonists, which could contribute to the hypertensive effects of high intakes of dietary salt.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, nutrition.

Hamann, J.J., J.B. Buckwalter, and P.S. Clifford (2004). Vasodilatation is obligatory for contraction-induced hyperaemia in canine skeletal muscle. Journal of Physiology (Oxford) 557(3): 1013-1020. ISSN: 0022-3751.
NAL Call Number: 447.8 J82
Abstract: There is a rapid increase in blood flow to active skeletal muscle with the onset of exercise, but the mechanism(s) eliciting this increase remains elusive. We hypothesized that the rapid increase in blood flow to active skeletal muscle with the onset of exercise is attributable to vasodilatation as a consequence of smooth muscle hyperpolarization. To test this hypothesis we examined the blood flow response to a brief tetanic contraction in which potassium (K+) was infused intra-arterially to elevate the (K+)o and clamp the smooth muscle membrane potential within the skeletal muscle vascular bed. In six anaesthetized beagle dogs control contractions increased hindlimb blood flow by 97 +/- 14 ml min-1. During K+ infusion the hyperaemic response to contraction was 8 +/- 3 ml min-1. Since the hindlimb blood flow was reduced during K+ infusion, a similar reduction in baseline blood flow was produced with phenylephrine infusion. During phenylephrine infusion the hyperaemic response to contraction was preserved (89 +/- 23 ml min-1). Recovery contractions performed after the discontinuation of the K+ infusion elicited blood flow responses similar to control (100 +/- 11 ml min-1). In a separate experimental protocol using the isolated gastrocnemius muscle of mongrel dogs (n = 6) K+ infusion did not alter force production by the skeletal muscle. Our data indicate that in the absence of vasodilatation, there is virtually no change in blood flow. One implication of this finding is that the muscle pump cannot be responsible for the initial contraction-induced hyperaemia. We conclude that the increase in blood flow immediately following a single muscle contraction is due to vasodilatation, presumably as a consequence of smooth muscle hyperpolarization.
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, contraction induced hyperemia, metabolic disease, blood flow response, hindlimb blood flow, recovery contractions, smooth muscle membrane potential, vasodilatation.

Hashimoto, N., I. Takeyoshi, H. Tsutsumi, Y. Sunose, M. Tokumine, O. Totsuka, S. Ohwada, K. Matsumoto, and Y. Morishita (2004). Effects of a bradykinin b2 receptor antagonist on ischemia-reperfusion injury in a canine lung transplantation model. Journal of Heart and Lung Transplantation 23(5): 606-613. ISSN: 1053-2498.
Abstract: Background: This study investigated the effects of a bradykinin B, receptor antagonist, FR173657 (FR), on ischemia-reperfusion (I/R) injury in a canine lung transplantation model. Methods: Eighteen pairs of weight-matched dogs were randomly divided into 3 groups. Six pairs were assigned to the FR(D+R) group, in which FR (100 nmol/kg/h) was administered to the transplant donor continuously beginning 30 minutes before ischemia until the onset of ischemia, and FR was administered to the transplant recipient beginning 30 minutes before reperfusion and continuing for 2 hours after reperfusion. Another 6 pairs of dogs were assigned to the FR(R) group, in which FR was administered only to the recipient in the same manner as in the FR(D + R) group. The other pairs were assigned to the control group, in which vehicle alone was administered. Orthotopic left lung transplantation was performed after 12-hour cold storage in Euro-Collins solution. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated. The animals were measured for 4 hours after reperfusion for left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (Pao2) and alveolar-arterial oxygen pressure difference (A-aDo2). Lung specimens were harvested for measurement of the wet-to-dry lung weight ratio (WDR), histopathologic studies and polymorphonuclear neutrophil (PMN) count. Results: Compared with the control group, Pao2, A-aDo2, L-PVR and CO were all significantly (p < 0.05) improved and WDR significantly (p < 0.05) lower in both the FR(D+R) and FR(R) groups. Moreover, in the FR-treatcd groups, histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced. Conclusions: The bradykinin B, receptor antagonist, FR173657, ameliorates I/R injury in lung grafts, indicating that protection of lung grafts can be achieved by the administration of FR solely to the transplant.
Descriptors: cardiovascular system, transport and circulation, pharmacology, respiratory system, respiration, ischemia reperfusion injury, injury, vascular disease, pathology, histopathologic study, histology and cytology techniques, laboratory techniques, lung transplantation, clinical techniques, therapeutic and prophylactic techniques, orthotopic left lung transplantation, alveolar arterial oxygen pressure difference, arterial oxygen pressure, cardiac output, left pulmonary vascular resistance, wet to dry lung weight ratio.

Hatada, K., L.M. Riou, M. Ruiz, R.L. Lima, A.R. Goode, D.D. Watson, G.A. Beller, and D.K. Glover (2003). Comparison between the myocardial uptake of 99mtcn-dbodc5 and 201ti during vasodilator stress in a canine model of a critical coronary stenosis. Journal of the American College of Cardiology 41(6 Supplement A): 443A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, metabolism, pharmacology, coronary stenosis, heart disease, vascular disease, myocardial blood flow, vasodilator stress.

Haushalter, T.M., G.S. Friedrichs, D.L. Reynolds, M. Barecki Roach, G. Pastino, R. Hayes, and A.S. Bass (2008). The cardiovascular and pharmacokinetic profile of dofetilide in conscious telemetered beagle dogs and cynomolgus monkeys. British Journal of Pharmacology 154(7): 1457-64. ISSN: 0007-1188.
NAL Call Number: 396.8 B77
Abstract: BACKGROUND AND PURPOSE: The effects of dofetilide were studied in monkeys and dogs. Pharmacokinetic data were generated together with the monitoring of cardiovascular changes in order to compare effects relative to human exposure. EXPERIMENTAL APPROACH: Beagle dogs and cynomolgus monkeys were telemetered to collect arterial blood pressure, heart rate and ECG for 6 h after selected oral doses of dofetilide. Pharmacokinetic parameters were determined for each dose. KEY RESULTS: Dogs: increases in the QT(c) interval reached 56 ms in dogs dosed with 0.3 mg kg(-1) of dofetilide. Premature ventricular contractions and right bundle branch block were evident at this dose, without changes in cardiovascular parameters. The mean C(max) values were 3.35 and 60.15 ng mL(-1) at doses of 0.03 and 0.3 mg kg(-1), respectively. Monkeys: increases in QT(c) intervals reached 40-50 ms after 0.03 mg kg(-1). T-wave changes were observed after 0.03 mg kg(-1) without changes in cardiovascular parameters. The mean C(max) values following oral doses of 0.01 and 0.03 mg kg(-1) were 0.919 ng mL(-1) and 1.85 ng mL(-1), respectively. CONCLUSIONS AND IMPLICATIONS: Despite dofetilide exposure comparable to that in humans, QT(c) responses in dogs were greater than those reported in humans. A comparable human dose used in the monkey achieved only half of the exposure but was associated with twofold greater increases in QT(c). Our data support the view that safety risk assessments of new drugs in animal models should ensure that the clinical therapeutic range of exposure is achieved and any untoward effects interpreted accordingly.
Descriptors: anti arrhythmia agents toxicity, long qt syndrome chemically induced, models, animal, phenethylamines toxicity, sulfonamides toxicity, administration, oral, anti arrhythmia agents administration and dosage, anti arrhythmia agents pharmacokinetics, blood pressure drug effects, dogs, dose response relationship, drug, electrocardiography, heart rate drug effects, macaca fascicularis, phenethylamines administration and dosage, phenethylamines pharmacokinetics, species specificity, sulfonamides administration and dosage, sulfonamides pharmacokinetics, telemetry.

He, K.L., M. Dickstein, H.N. Sabbah, G.H. Yi, A. Gu, M. Maurer, C.M. Wei, J. Wang, and D. Burkhoff (2004). Mechanisms of heart failure with well preserved ejection fraction in dogs following limited coronary microembolization. Cardiovascular Research 64(1): 72-83. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Descriptors: animal model, induced myocardial injury, hemodynamics, microembolization, neurohormonal activation, cardiovascular system, heart failure, heart disease, etiology, coronary microembolization, diastolic dysfunction, ejection fraction, neurohormonal activation.

He, K.L., W. Hadad, G.H. Yi, H. Zhou, S. Mohri, J. Wang, and D. Burkhoff (2003). Nonexcitatory electric signals improve systemic hemodynamics and cardiac contractility in conscious dogs with chronic heart failure. Journal of the American College of Cardiology 41(6 Supplement A): 89A ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, chronic heart failure, heart disease, left ventricular function, chronic heart failure effects, nonexcitatory electric signal induced improvement, systemic hemodynamics.

He, K.L., W. Sherman, G.H. Yi, Q. Li, H. Zhou, E.M. Becker, A.G. Gu, J. Harvey, E. Rose, H.B. Haimes, R. Kao, G.P. Zhang, M.J. Lee, J. Wang, and D. Burkhoff (2003). Autologous skeletal myoblast transplantation improves hemodynamics and left ventricular regional and global function in conscious dogs with chronic heart failure. Cell Transplantation 12(2): 146. ISSN: 0963-6897.
NAL Call Number: RM287.C45
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, surgery, medical sciences, veterinary medicine, chronic heart failure, heart disease, autologous skeletal myoblast transplantation, laboratory techniques, echocardiography, clinical techniques, diagnostic techniques, inferior vena cava occlusion, experimental surgical techniques, skeletal muscle biopsy, ejection fraction, hemodynamics, mean aortic pressure, regional segment length, determination.

Hobai, I.A., C. Maack, and B. O'rourke (2004). Partial inhibition of sodium/calcium exchange restores cellular calcium handling in canine heart failure. Circulation Research 95(3): 292-299. ISSN: 0009-7330.
NAL Call Number: RC681.A1A57137
Abstract: Sodium/calcium (Na+/Ca2+) exchange (NCX) overexpression is common to human heart failure and heart failure in many animal models, but its specific contribution to the cellular Ca2+ ((Ca2+)i) handling deficit is unclear. Here, we investigate the effects of exchange inhibitory peptide (XIP) on Ca2+ handling in myocytes isolated from canine tachycardic pacing-induced failing hearts. Whole-cell patch-clamped left ventricular myocytes from failing hearts ( F) showed a 52% decrease in steady-state sarcoplasmic reticulum (SR) Ca2+ load and a 44% reduction in the amplitude of the (Ca2+)i transient, as compared with myocytes from normal hearts (N). Intracellular application of XIP (30 mumol/L) normalized the (Ca2+)i transient amplitude in F (3.86-fold increase), concomitant with a similar increase in SR Ca2+ load. The degree of NCX inhibition at this concentration of XIP was apprxeq27% and was selective for NCX: L-type Ca2+ currents and plasmalemmal Ca2+ pumps were not affected. XIP also indirectly improved the rate of (Ca2+)i removal at steady-state, secondary to Ca2+-dependent activation of SR Ca2+ uptake. The findings indicate that in the failing heart cell, NCX inhibition can improve SR Ca2+ load by shifting the balance of Ca2+ fluxes away from trans-sarcolemmal efflux toward SR accumulation. Hence, inhibition of the Ca2+ efflux mode of the exchanger could potentially be an effective therapeutic strategy for improving contractility in congestive heart failure.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, veterinary medicine, medical sciences, congestive heart failure.

Ishizaka, T., A. Takahara, H. Iwasaki, Y. Mitsumori, H. Kise, Y. Nakamura, and A. Sugiyama (2008). Comparison of electropharmacological effects of bepridil and sotalol in halothane-anesthetized dogs. Circulation Journal Official Journal of the Japanese Circulation Society 72(6): 1003-11. ISSN: 1346-9843.
Abstract: BACKGROUND: Bepridil is known to have a multiple ion channel-blocking property in the heart, which has been applied for the treatment of atrial fibrillation and drug-refractory ventricular tachyarrhythmias. In this study, the electro-pharmacological effects of bepridil were compared with those of dl-sotalol, a representative class III antiarrhythmic drug, using the halothane-anesthetized canine model. METHODS AND RESULTS: Cardiovascular and electrophysiological variables were measured under the halothane anesthesia. Intravenous administration of bepridil (0.3 mg/kg, n=4) delayed the intraventricular conduction and prolonged the ventricular effective refractory period, whereas dl-sotalol (0.3 mg/kg, iv, n=4) inhibited atrioventricular conduction and prolonged the atrial and ventricular effective refractory period. The additional administration of 10 times the higher dose of bepridil or dl-sotalol (ie, 3 mg/kg, iv, n=4 for each group) decreased blood pressure, suppressed ventricular contraction and sinus automaticity, and prolonged the atrial and ventricular effective refractory period and monophasic action potential duration, in addition to the effects of the low dose. CONCLUSIONS: The electropharmacological effects of bepridil and dl-sotalol were similar, although their potency for each cardiovascular variable varied significantly. These findings can be useful when selecting these drugs according to the pathophysiological condition of a patient.
Descriptors: adrenergic beta antagonists pharmacology, bepridil pharmacology, heart conduction system drug effects, sotalol pharmacology, vasodilator agents pharmacology, adrenergic beta antagonists blood, anesthetics, inhalation, atrioventricular node drug effects, bepridil blood, bundle of his drug effects, dogs, dose response relationship, drug, electrocardiography drug effects, halothane, models, animal, myocardial contraction drug effects, pacemaker, artificial, sinoatrial node drug effects, sotalol blood, vasodilator agents blood.

Ito, B.R., J. Ryan, S.C. Potter, and M.A. Young (1995). Contractile dysfunction with arbutamine stress correlates with heart rate in conscious dog with coronary stenosis. Circulation 92(8 SUPPL.): I479. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, coronary artery disease, diagnostic method, meeting abstract

Kador, P.F., K. Blessing, and M. Wyman (2003). The results of combretastatin in galactose - fed dogs with diabetes - like proliferative retinopathy. Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, USA; May 04-08, 2003,
Abstract: Purpose: Combretastatin A-4 (CA4P) is a vascular targeting agent that has been reported to be capable of destroying newly formed capillary endothelial cells in growing vessels. The net effect of this drug has been to rapidly shut off blood flow in newly growing vessels and, as a result, regress neovascularization. The purpose of this study was to determine whether retinal neovascularization which results in altered retinal vessel blood flow and retinal permeability in the long-term galactose-fed dog can be halted with CA4P. Methods: All experiments conform to the ARVO Resolution on the Use of Animals in Research and NIH ACUC Guidelines. Eight beagles fed 30% galactose diet for 80-104 months and four age-matched control dogs were surgically made aphakic. Following recovery the dogs were divided into two groups each containing 4 galactose-fed dogs and 2 age-matched controls dogs with each group receiving CA4P either as sub-Tenon's injections administered at the corneoscleral junction or intravitreal injections. Six weeks after initial CA4P treatment all dogs also received systemic (IV) injections of CA4P. The extent of neovascularization and affect of CA4P administration were monitored by fluorescein angiography and color and monochromatic fundus photography at 2-week intervals. Results: Although CA4P was well tolerated by the healthy eyes of the control animals its administration to galactose-fed dogs was associated with corneal edema and increases in IOP after sub-Tenon's and intraocular injections. All galactose-fed dogs demonstrated retinal neovascular lesions and these were not ameliorated by either sub-Tenon's, intravitreal or systemic CA4P administration. Conclusions: Neovascularization in this animal model progresses over a period of years similar to that observed clinically. The failure of CA4P to ameliorate neovascularization suggests that chronic, long-term administration is required to destroy the slowly growing retinal endothelial cells.
Descriptors: cardiovascular system, transport and circulation, metabolism, pharmacology, sense organs, sensory reception, aphakia, eye disease, diabetes like proliferative retinopathy, endocrine disease, pancreas, metabolic disease, retinal blood vessel blood flow, retinal neovascularization.

Karapinar, K., A.T. Ulus, U. Tutun, A. Aksoyek, N. Apaydin, K. Pamuk, Z. Can, Z. Saritas, F. Kucukay, K. Arda, and S.F. Katircioglu (2004). Implantation of novel small-diameter polyurethane vascular prostheses interposed in canine femoral and carotid arteries. European Surgical Research 36(4): 241-248. ISSN: 0014-312X.
Descriptors: bioprocess engineering, cardiovascular system, transport and circulation, scanning electron microscopy, imaging and microscopy techniques, laboratory techniques, vascular grafts, small diameter polyurethane vascular prosthesis, carotid artery interposition, femoral artery interposition.

Kassotis, J., R.B. Sauberman, C. Cabo, A.L. Wit, and J. Coromilas (2003). Beta receptor blockade potentiates the antiarrhythmic actions of d-sotalol on reentrant ventricular tachycardia in a canine model of myocardial infarction. Journal of Cardiovascular Electrophysiology 14(11): 1233-1244. ISSN: 1045-3873.
Abstract: Introduction: The importance of beta receptor blockade for the antiarrhythmic action of sotalol has not been completely elucidated. We determined how beta receptor blockade interacts with the effects of potassium channel blockade on reentrant circuits. Methods and Results: Sustained ventricular tachycardia was induced by programmed stimulation in dogs 4 days after left anterior coronary artery occlusion and reentrant circuits in the epicardial border zone (EBZ) mapped. The effects of the beta receptor-blocking drug, esmolol, the potassium channel-blocking drug d-sotalol, which lacks beta receptor-blocking effects, and the combination of the two drugs on the reentrant circuits that cause tachycardia were determined. Esmolol did not alter the ability to induce tachycardia. Small changes in the location or extent of lines of block in reentrant circuits accounted for small decreases or increases in tachycardia cycle lengths. d-Sotalol prolonged the lines of block in reentrant circuits, slowed propagation around the circuits, and prolonged tachycardia cycle length, but it did not stop tachycardia or prevent the induction of tachycardia. The combination of esmolol and d-sotalol prevented the initiation of sustained tachycardia. The stimulated premature impulse either blocked before reentering or traversed the circuit several times prior to blocking in a region of fractionated electrograms. The addition of esmolol to d-sotalol abolished the reverse use-dependent effects of d-sotalol alone on effective refractory period (ERP) and significantly prolonged ERP in the area of the reentrant circuit. Conclusion: Beta receptor blockade is important for the antiarrhythmic effects of d,l-sotalol on reentrant ventricular tachycardia in this model. The mechanism is speculative but may involve potentiation of d-sotalol actions to prolong ERP or effects on gap junctions.
Descriptors: cardiovascular system, transport and circulation, coronary artery occlusion, heart disease, reentrant ventricular tachycardia, effective refractory period.

Kast, R., H. Schirok, S. Figueroa Perez, J. Mittendorf, M.J. Gnoth, H. Apeler, J. Lenz, J.K. Franz, A. Knorr, J. Hutter, M. Lobell, K. Zimmermann, K. Munter, K.H. Augstein, H. Ehmke, and J.P. Stasch (2007). Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase. British Journal of Pharmacology 152(7): 1070-80. ISSN: 0007-1188.
NAL Call Number: 396.8 B77
Abstract: BACKGROUND AND PURPOSE: Rho-kinase (ROCK) has been implicated in the pathophysiology of altered vasoregulation leading to hypertension. Here we describe the pharmacological characterization of a potent, highly selective and orally active ROCK inhibitor, the derivative of a class of azaindoles, azaindole 1 (6-chloro-N4-{3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-phenyl}pyrimidine-2,4-diamine). EXPERIMENTAL APPROACH: Pharmacological characterization of azaindole 1 was performed with human recombinant ROCK in vitro. Vasodilator activity was determined using isolated vessels in vitro and different animal models in vivo. KEY RESULTS: This compound inhibited the ROCK-1 and ROCK-2 isoenzymes with IC50 s of 0.6 and 1.1 nM in an ATP-competitive manner. Although ATP-competitive, azaindole 1 was inactive against 89 kinases (IC50>10 microM) and showed only weak activity against an additional 21 different kinases (IC50=1-10 microM). Only the kinases TRK und FLT3 were inhibited by azaindole 1 in the sub-micromolar range, albeit with IC50 values of 252 and 303 nM, respectively. In vivo, azaindole 1 lowered blood pressure dose-dependently after i.v. administration in anaesthetized normotensive rats. In conscious normotensive and spontaneously hypertensive rats azaindole 1 induced a dose-dependent decrease in blood pressure after oral administration without inducing a significant reflex increase in heart rate. In anaesthetized dogs, azaindole 1 induced vasodilatation with a moderately elevated heart rate. CONCLUSIONS AND IMPLICATIONS: Azaindole 1 is representative of a new class of selective and potent ROCK inhibitors and is a valuable tool for the elucidation of the role of ROCK in the cardiovascular system.
Descriptors: cardiovascular system drug effects, diamines pharmacology, protein kinase inhibitors pharmacology, pyrimidines pharmacology, rho associated kinases antagonists and inhibitors, administration, oral, apoptosis regulatory proteins antagonists and inhibitors, apoptosis regulatory proteins genetics, apoptosis regulatory proteins metabolism, binding sites drug effects, blood pressure drug effects, calcium calmodulin dependent protein kinases antagonists and inhibitors, calcium calmodulin dependent protein kinases genetics, calcium calmodulin dependent protein kinases metabolism, cells, cultured, computer simulation, dogs, dose response relationship, drug, injections, intravenous, mice, models, animal, models, molecular, organ culture techniques, phosphorylation, polymerase chain reaction methods, protein kinase inhibitors administration and dosage, protein kinase inhibitors chemistry, rabbits, rats, rats, inbred shr, rats, wistar, recombinant proteins antagonists and inhibitors, recombinant proteins genetics, recombinant proteins metabolism, time factors, vasodilator agents administration and dosage, vasodilator agents chemistry, vasodilator agents pharmacology, rho associated kinases genetics, rho associated kinases metabolism.

Kawase, A., T. Ikeda, K. Nakazawa, T. Ashihara, T. Namba, T. Kubota, K. Sugi, and H. Hirai (2003). Widening of the excitable gap and enlargement of the core of reentry during atrial fibrillation with a pure sodium channel blocker in canine atria. Circulation 107(6): 905-910. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background: This study aimed to assess the effects of pilsicainide, a pure sodium channel blocker, on electrophysiological action and wavefront dynamics during atrial fibrillation (AF). Methods and Results: In a newly developed model of isolated, perfused, and superfused canine atria (n=12), the right and left endocardia were mapped simultaneously by use of a computerized mapping system. AF was induced with 1 to 5 mumol/L acetylcholine. The antifibrillatory actions of pilsicainide on AF cycle length (AFCL), refractory period (RP), conduction velocity (CV), excitable gap (EG), and the core of the mother rotor were studied. The RP was defined as the shortest coupling interval that could capture the fibrillating atrium. The EG was estimated as the difference between the AFCL and RP. At baseline, multiple wavefronts were observed. After 2.5 mug/mL infusion of pilsicainide, all preparations showed irregular activity, and AF was terminated in 2 preparations. The AFCL and RP were prolonged, and CV was decreased significantly. The EG was widened (147%; P<0.01), and the core perimeter was increased (100%; P<0.01). Increasing the dosage either terminated AF (6 preparations) or converted to organized activity (ie, atypical atrial flutter) (4 preparations). On the maps, all "unorganized" AFs were terminated with the excitation of the core of the mother rotor by an outside wavefront, whereas in preparations with atrial flutter, pilsicainide did not terminate its activity. Conclusions: Widening of the EG by pilsicainide facilitates the excitation of the core of the mother rotor, leading to the termination of AF. In some experiments, pilsicainide converts AF to persistent atrial flutter.
Descriptors: cardiovascular system, transport and circulation, pharmacology, atrial fibrillation, heart disease, drug therapy, pathology, electrophysiology, clinical techniques, conduction velocity, cycle length, excitable gap widening, reentry core enlargement, refractory period, wavefront dynamics.

Keenan, C.M. and J.D. Vidal (2006). Standard morphologic evaluation of the heart in the laboratory dog and monkey. Toxicologic Pathology 34(1): 67-74. ISSN: 0192-6233.
Abstract: The nonrodent species most commonly utilized in preclinical safety studies are the purpose-bred beagle dog and cynomolgus macaque (Macaca fascicularis). Potential effects of a new chemical entity (NCE) on the heart pose serious concerns; consequently in vivo testing is focused on detection of functional alterations as well as morphological changes. Macroscopic and microscopic evaluation of the heart is based on a standard survey of key structures to properly assess presence of spontaneous and potential drug-induced lesions. Evaluation of historical controls to determine type and frequency of background change is valuable, as studies with non-rodent species generally have a small sample size. Archived control dog and monkey data were retrospectively reviewed, including terminal body weight (BW), heart weight (HW), and archival glass slides of heart. Control dogs had minimal background changes that included myxomatous or cartilagenous change in the cardiac skeleton and a variable degree of vacuolation in Purkinje fibers. Control monkey hearts commonly contained inflammatory cell infiltrates, myocyte anisokaryosis, and handling artifacts, while myocyte degeneration, squamous plaques, pigment, and intimal plaques were occasionally observed. These findings highlight the utility of consistently recorded and readily accessible archived control data when attempting to discern background spontaneous changes and artifacts from test-article induced changes.
Descriptors: dogs anatomy and histology, heart anatomy and histology, macaca fascicularis anatomy and histology, specimen handling standards, toxicity tests standards, body weight, drug evaluation, preclinical, organ size, reference values, species specificity, specimen handling methods, toxicity tests methods.

Kelly, C.M., M. Miyamoto, and S.J. Gosselin (2003). Validation for qt prolongation in conscious beagle dogs administered sotalol via the oral route. Toxicological Sciences 72(S-1): 32 ISSN: 1096-6080.
NAL Call Number: RA1190.F8
Descriptors: cardiovascular system, transport and circulation, pharmacology, toxicology, DSI telemetry system, medical equipment, williams test, laboratory techniques, implanted telemetry transmitters, medical supplies, ECG waveform, qt prolongation, blood pressure, heart rate.

Kemming, G., J.B. Messick, W. Mueller, G. Enders, F. Meisner, S. Muenzing, H. Kisch Wedel, A. Schropp, C. Wojtczyk, K. Packert, K. Messmer, and E. Thein (2004). Can we continue research in splenectomized dogs? Mycoplasma haemocanis: old problem - new insight. European Surgical Research 36(4): 198-205. ISSN: 0014-312X.
Descriptors: cardiovascular system, transport and circulation, infection, Mycoplasma haemocanis infection, bacterial disease, diagnosis, therapy, blood smear, diagnostic techniques, laboratory techniques, specific polymerase chain reaction, genetic techniques.

Kerbaul, F., B. Rondelet, S. Motte, P. Fesler, I. Hubloue, P. Ewalenko, R. Naeije, and S. Brimioulle (2004). Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure. Critical Care Medicine 32(4): 1035-40. ISSN: 0090-3493.
Abstract: OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects norepinephrine and dobutamine on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-two anesthetized dogs. INTERVENTIONS: Animals underwent transient (90-min) PA constriction to induce persistent RV failure. They were randomly assigned to control, norepinephrine, or dobutamine group. Norepinephrine was administered at 0.1 and 0.5 microg x kg x min or dobutamine at 5 and 10 microg x kg x min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We also measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. The transient PA constriction persistently increased PA resistance and elastance, increased Ea from 0.8+/-0.1 to 2.7+/-0.3 mmHg/mL, decreased Ees from 1.1+/-0.1 to 0.5+/-0.1 mm Hg/mL, and decreased Ees/Ea from 1.2+/-0.1 to 0.2+/-0.1. Norepinephrine restored arterial pressure, increased RV contractility, and increased but did not normalize RV-PA coupling and cardiac output. Dobutamine restored arterial pressure, markedly increased RV contractility, and normalized RV-PA coupling and cardiac output. Compared with norepinephrine, dobutamine decreased PA resistance and elastance and increased RV contractility and RV-PA coupling. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Dobutamine restores RV-PA coupling and cardiac output better than norepinephrine because of its more pronounced inotropic effect.
Descriptors: animal model, pulmonary arterial (PA) pressure, right ventricular (RV) contractility, cardiac output, norepinephrine, dobutamine.

Kim, J.T., K.Y. Rhee, J.H. Bahk, S.H. Do, Y.J. Lim, H. Ko, and K.H. Lee (2003). Continuous mixed venous oxygen saturation, not mean blood pressure, is associated with early bupivacaine cardiotoxicity in dogs. Canadian Journal of Anesthesia 50(4): 376-381. ISSN: 0832-610X.
Abstract: Purpose: To investigate changes of continuous mixed venous oxygen saturation (cSvO2) and mean arterial blood pressure (MBP) in dogs with bupivacaine-induced cardiac depression. Methods: Bupivacaine was infused into pentobarbital-anesthetized mongrel dogs (n=8) at a rate of 0.5 mgcntdotkg-1cntdotmin-1 until the MBP was 40 mmHg or less (end of bupivacaine infusion; BIE). The infusion time was divided into the early period, first 30 min of bupivacaine infusion and the late period, which was from 30 min of bupivacaine infusion until BIE. cSvO2 was monitored using a fibreoptic pulmonary artery catheter, and MBP and cardiac output (CO) were measured every ten minutes after the initiation of bupivacaine infusion. Arterial blood gas, serum electrolyte and bupivacaine concentration were measured simultaneously. The relationships between CO and cSvO2, and of CO vs MBP were compared by regression analysis in the early and late periods. Results: The Pearson's correlation coefficients between CO and cSvO2 were 0.782 (P=2.1X10-7) in the early period and 0.824 (P=1.3X10-6) in the late period. The correlation coefficients between CO and MBP were 0.019 (P=0.921) in the early period and 0.799 (P=4.8X10-6) in the late period. Conclusions: cSvO2, but not MBP, is associated with CO changes in bupivacaine-induced cardiac depression during the early period of bupivacaine intoxication. Decrease of MBP with low cSvO2 observed during the late period might imply severe cardiac depression induced by bupivacaine infusion.
Descriptors: cardiovascular system, transport and circulation, pharmacology, toxicology, bupivacaine induced cardiac depression, heart disease, toxicity, continuous mixed venous oxygen saturation, bupivacaine induced cardiotoxicity association, mean blood pressure.

Kita, T., K. Kubo, I. Narushima, S. Matsumura, Y. Yonetani, and T. Nakashima (1996). Behavioral effects and role of endothelin in a canine subarachnoid model. Japanese Journal of Pharmacology 71(SUPPL. 1): 91P. ISSN: 0021-5198.
Descriptors: behavior, cardiovascular system, transport and circulation, endocrine system, chemical coordination and homeostasis, nervous system, neural coordination, animal model, basilar artery caliber, behavioral effect, cerebral vasospasm, endocrine system, endothelin 1, meeting poster, meningeal sign, nervous system disease, severe ataxia, subarachnoid hemorrhage, vascular disease.

Kobayashi, T., K. Ashikaga, M. Kimura, K.I. Furukawa, K. Seya, T. Osanai, K. Okumura, and S. Motomura (2004). Rapid atrial pacing upregulates synthesis of asymmetrical dimethylarginine and expression of protein arginine n-methyltransferases in canine af model. Journal of Pharmacological Sciences 94(Supplement 1): 107P. ISSN: 1347-8613.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, atrial fibrillation, heart disease, rt pcr, reverse transcriptase polymerase chain reaction, genetic techniques, laboratory techniques, rapid atrial pacing, clinical techniques, therapeutic and prophylactic techniques.

Koide, M., S. Nishizawa, M. Yamaguchi, Y. Nonaka, and H. Namba (2004). Chronological changes of diameter, functional properties, and morphology of vasospastic artery in canine two-hemorrhage model. Journal of Pharmacological Sciences 94(Supplement 1): 94P. ISSN: 1347-8613.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, models and simulations, computational biology, hemorrhage, vascular disease, chronological changes, two hemorrhage model.

Koike, N., I. Takeyoshi, S. Ohki, M. Tokumine, K. Matsumoto, and Y. Morishita (2004). Effects of adding p38 mitogen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors. Transplantation 77(2): 286-292. ISSN: 0041-1337.
NAL Call Number: QP89.T73
Abstract: Background: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in ischemia-reperfusion injury. This study evaluated the effects of p38 MAPK inhibition using FR167653, a novel p38 MAPK inhibitor, as an additive to Celsior solution in canine heart transplantation from non-heart-beating donors (NHBDs). Methods: Donor hearts were left in situ for 20 minutes after cardiac arrest, which was induced by rapid exsanguination. Twelve donor-recipient pairs of mongrel dogs were divided into two groups: the control and FR167653 (FR) groups (n=6 each). In both groups, the grafts were subjected to coronary flushing and immersed in Celsior solution for 4 hours with or without FR167653. Orthotopic heart transplantation was then performed. Cardiac output (CO), left ventricular pressure (LVP), and end-systolic maximal elastance (Emax) were measured 2 hours after weaning from cardiopulmonary bypass (CPB), and the hearts were then harvested for histopathologic study. The activation of p38 MAPK was evaluated in another 20 mongrel dogs. Results: In the FR group, CO, LVP recovery rate, and Emax were significantly (P<0.05) higher 2 hours after weaning from CPB, histopathologic damage was attenuated, and the activation of p38 MAPK was significantly (P<0.05) inhibited 10 minutes after reperfusion compared with the control group. Conclusions: The addition of FR167653 to Celsior solution improved heart-graft viability, probably by way of the inhibition of p38 MAPK activation, which may attenuate ischemia-reperfusion injury in heart transplantation from NHBDs.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, ischemia reperfusion injury, vascular disease, heart transplantation, experimental surgical techniques, laboratory techniques, celsior solution, non heart beating donor.

Kojima, J., S. Niwano, M. Moriguchi, K. Ikeda, K. Inuo, J. Saito, and T. Izumi (2003). Effect of pilsicainide on atrial electrophysiologic properties in the canine rapid atrial stimulation model: a possible suppressive effect on atrial electrical remodeling. Circulation Journal 67(4): 340-346. ISSN: 1346-9843.
Abstract: The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening (DELTAAERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these DELTAAERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intra-atrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na-Ca exchanger.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, atrial fibrillation, heart disease, atrial stimulation model, laboratory techniques, atrial effective refractory period, atrial electrical remodeling, atrial electrophysiology, ventricular heart rate.

Krause, S.-M., F.-C. Clayton, and D.-L.-J. Williams (2004). Myocardial protection with the non-selective endothelin receptor antagonist l-753,037 following acute coronary artery occlusion in the dog. Journal of Cardiovascular Pharmacology 43(2): 214-221. ISSN: 0160-2446.
Abstract: Efficacy of a new, potent non-selective endothelin antagonist, L-753037, was examined in a model of canine coronary artery occlusion and reperfusion to assess whether blockade of both ETA and ETB receptors would enhance or reduce myocardial ischemic injury. Instrumented dogs were randomized to receive vehicle (n=9) or L-753037 (0.1 mug/kg/min, n=9) by intracoronary infusion 30 minutes before a 90-minute LCx coronary artery occlusion and through 4 hours of reperfusion. After 4 hours of reperfusion, plasma ET-1 levels rose significantly in both groups: 24+-3 fmol/ml in vehicle animals (P<0.01) versus 42+-5 fmol/ml with L-753037 (P<0.05). Treatment with L-753037 normalized total LCx flow and regional myocardial flow after 4 hours of reperfusion in all regions. LCx flow was reduced 16% from pre-occlusion baseline (P=0.45) with treatment compared with 35% with vehicle (P<0.01). Endocardial flow in the risk region returned to baseline values with L-753037 treatment but was reduced apprx50% in vehicle animals. L-753037 treatment was associated with a 38% reduction in infarct size (24.1+-3.9% AAR with L-753037 treatment versus 38.7+-3.1% with vehicle, P<0.01). Thus, a non-selective endothelin antagonist provides significant myocardial protection primarily by improving regional myocardial flow distribution following reperfusion and demonstrated no detrimental effects associated with blockade of the ETB receptor.
Descriptors: cardiovascular system, transport and circulation, pharmacology, acute coronary artery occlusion, vascular disease, myocardial ischemic injury, heart disease, injury, myocardial protection.

Krolikowski, J.G., W. Gu, J.P. Tessmer, P.S. Pagel, D.C. Warltier, and J.R. Kersten (2004). Sildenafil enhances coronary collateral development in dogs with diabetes. FASEB Journal 18(4-5): Abst. 437.7. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: nitric oxide, phosphodiesterase fraction V inhibitor sildenafil, pharmacology, cardiovascular system, transport and circulation, endocrine system, chemical coordination and homeostasis, diabetes mellitus, endocrine disease, pancreas, metabolic disease, coronary collateral development.

Kucukhuseyin, C. (2003). Cardiovascular effects of intravenous pentazocine and cyclazocine in conscious, curarized-conscious, and anesthetized dogs. Journal of Basic and Clinical Physiology and Pharmacology 14(3): 235-255. ISSN: 0792-6855.
Abstract: The cardiovascular effects of intravenous pentazocine and cyclazocine in dogs were studied under conscious, curarized-conscious (paralyzed by gallamine), and anesthetized states. In the conscious state, blood pressure and heart rate were dose-dependently increased by pentazocine (1, 2, 3 mg/kg) and to a lesser extent by cyclazocine (0.3 mg/kg). In all subsequent experiments on dogs, the results were obtained using 3 mg/kg pentazocine and 0.3 mg/kg cyclazocine. Pentazocine accelerated breathing, peaking at about 10 min, whereas cyclazocine reduced breathing to a minimum in 1 min, followed by a gradual recovery thereafter. In the curarized-conscious state, the blood pressure response to pentazocine was biphasic, namely an initial decrease followed by an increase; chronotrophic activity was stimulated. Pretreatment with either ganglionic or alpha andrenergic blocking agents not only significantly antagonized the pressory responses to the drug but also potentiated the initial decreases in blood pressure and unmasked a bradycardic component, but these parameters were not altered by 0.3 mg/kg naxalone. In open-chest anesthetized dogs, blood pressure, heart rate, contractility, and mean peripheral vascular resistance were simultaneously decreased by both pentazocine and cyclazocine, initially accompanied by increases in aortic blood flow. During the later stages of drug action, only the blood pressure and contractility were increased above control levels (biphasic effect). A comparison of blood pressure and heart rate responses to pentazocine in dogs kept under differing experimental conditions revealed that conscious dogs were more sensitive than curarized conscious and anesthetized animals to pentazocine action. In isolated guinea pig atria, the effect of adrenaline (0.1, 0.3, or 1 mg/mL) on the spontaneous breathing rate was significantly augmented by 10 mg/mL pentazocine (p<0.02 for 0.3 g/mL; p<0.01 for 0.1 g/mL adrenaline). In dogs, however, adrenaline (1 mg/kg)-induced increases in heart contractility, aortic blood flow, and blood pressure remained almost unaltered in the presence of pentazocine. We concluded that the above mentioned cardiovascular responses to pentazocine and cyclazocine are a consequence of the sum of the two following opposing effects: (i) an indirect reflex activation of sympathetic neuromediation in the periphery, and (ii) a direct membrane effect on the heart leading to bradycardia and a depression in myocardial contractility.
Descriptors: cardiovascular system, transport and circulation, pharmacology, curarization, experimental surgical techniques, laboratory techniques, blood pressure, conscious state, heart rate.

Kumagai, K., H. Nakashima, N. Gondo, and K. Saku (2003). Antiarrhythmic effects of jtv-519, a novel cardioprotective drug, on atrial fibrillation/flutter in a canine sterile pericarditis model. Journal of Cardiovascular Electrophysiology 14(8): 880-884. ISSN: 1045-3873.
Abstract: Introduction: A new cardioprotective drug, JTV-519, blocks Na+ current and inwardly rectifying K+ current and inhibits Ca2+ current. However, its role in atrial electrophysiology is unknown. We investigated the antiarrhythmic effects of JTV-519 on atrial fibrillation/flutter in the canine sterile pericarditis model. Methods and Results: In nine dogs with sterile pericarditis, 38 episodes of sustained (>30 sec) atrial fibrillation (8 dogs) and 24 episodes of sustained atrial flutter (7 dogs) were induced by rapid atrial pacing. When atrial fibrillation or atrial flutter was sustained >15 minutes, it was cardioverted and reinduced. The inducibility of atrial fibrillation/flutter, the atrial effective refractory period, and the intra-atrial conduction time were compared before and after the continuous infusion of JTV-519 (0.03 mg/kg/min). JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2+-2.9 to 0+-0, P<0.01). In contrast, atrial flutter was still inducible in 4 dogs after JTV-519 (from 2.7+-2.5 to 1.6+-2.1, P=NS). JTV-519 significantly prolonged effective refractory period (from 123+-18 to 143+-14 msec, from 127+-18 to 151+-12 msec, and from 132+-13 to 159+-9 msec at basic cycle lengths of 200, 300, and 400 msec, respectively, P<0.01), but it did not affect the intra-atrial conduction time (from 47+-11 msec to 48+-11 msec, P=NS). Conclusion: JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.
Descriptors: cardiovascular system, transport and circulation, pharmacology, atrial fibrillation, heart disease, drug therapy, atrial flutter, heart disease, drug therapy, sterile pericarditis, electrophysiology, clinical techniques, atrial effective refractory period, calcium ion current, intra atrial conduction time, inwardly rectifying potassium ion current, sodium ion current.

Kumagai, K., H. Nakashima, and K. Saku (2003). The hmg-coa reductase inhibitor atorvastatin prevents atrial fibrillation by inhibiting inflammation in the canine sterile pericarditis model. Journal of the American College of Cardiology 41(6 Supplement A): 90A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, pharmacology, atrial fibrillation, heart disease, therapy, sterile pericarditis.

Kuniyoshi, T., Y. Kakihana, S. Isowaki, Y. Kanmura, and M. Tamura (2002). Evaluation of cytochrome oxidase signal obtained by near-infrared spectroscopy during cardiopulmonary bypass in a dog model. 2002 Annual Meeting of the American Society of Anesthesiologists, Orlando, FL, USA; October 12-16, 2002,
Online: http://www.asa-abstracts.com
Abstract: Although the signal obtained for cytochrome oxidase (cyt. ox.) by near-infrared spectroscopy (NIRS) should be a useful indicator of intracellular hypoxia and impending cerebral injury, the change in the cyt. ox. signal represents a small component of the total change, and is therefore vulnerable to artifact. Accordingly, data interpretation, especially of the cyt. ox. value, remains controversial. We have developed a new approach to the measurement of the redox state of cyt. ox. in the brain involving the use of our new algorithm, which has already been employed in clinical medicine1. In this paper, we used two different NIRS devices to examine possible cross-talk between the cytochrome and hemoglobin (Hb) signals while a change was occurring in the hematocrit. Methods: After institution of cardiopulmonary bypass (CPB), an aerobic (100% O2)-to-anaerobic (100% N2) transition was induced using a membrane oxygenator in 12 dogs to produce a maximum change (full scale) in cerebral oxygenation. After stabilization for 10 min under 100% O2, animals received 200 mg/kg of sodium cyanide to uncouple cytochrome from Hb. The hematocrit was then decreased from 35 to 5% by hemodilution. During the experiments, the Hb and cytochrome signals were measured and calculations performed using two types of NIRS instrument: (1) NIRO 300 device (Hamamatsu Photonics Co., Hamamatsu, Japan), (2) OM 110 device (using our recently developed algorithm) (Shimadzu Co., Kyoto, Japan). Results: In this study, the Hb concentration calculated by either NIRS device (NIRO 300 or OM 110) showed a strong positive correlation with hematocrit values during hemodilution (NIRO 300: R2 = 0.96, p < 0.0001; OM 110: R2 = 0.98, p < 0.0001). Although the hemodilution resulted in a linear decrease in the cyt. ox. signal measured by the NIRO 300 device (R2 = 0.90, p < 0.0001), there was no correlation between the hematocrit value and the cyt. ox. signal measured by OM 110. Furthermore, the change in the cyt. ox. signal measured by OM 110 during hemodilution (from 35 to 5% Ht) was only 4 % of full scale. Discussion: After administration of a saturating quantity of sodium cyanide, mitochondrial oxygen consumption should be completely inhibited and the cyt. ox. signal should be independent of both the cerebral oxygen saturation and Hb concentration. Our data showed that the cyt. ox. signal calculated using our recently developed algorithm (OM 110 device) was not much influenced by hematocrit, but it showed a positive correlation with pump flow and hypoxia. However, the NIRO 300 device was unable to separate the Hb and cytochrome oxidase components during an attenuation, leading to artifactual changes in the cytochrome signal. In conclusion, the cyt. ox. signal measured by NIRS is dependent on the algorithm employed. Therefore, provided an accurate algorithm is employed the cyt. ox. signal measured by NIRS should provide us with important information even under CPB.
Descriptors: cardiovascular system, transport and circulation, cerebral injury, injury, nervous system disease, cardiopulmonary bypass, clinical techniques, therapeutic and prophylactic techniques, near infrared spectroscopy, laboratory techniques, spectrum analysis techniques, intracellular hypoxia.

Laky, D., L. Parascan, and V. Candea (2008). Myocardial stunning. Morphological studies in acute experimental ischemia and intraoperatory myocardial biopsies. Romanian Journal of Morphology and Embryology; Revue Roumaine De Morphologie Et Embryologie 49(2): 153-8. ISSN: 1220-0522.
Abstract: Myocardial stunning represent a consequence of brief ischemia with reversible regional contractile dysfunction dependent persist from minute to days after reperfusion, despite the absence of irreversible damage and restoration of coronary blood flow. The evolution of these new ischemic entity were described by experimental acute ischemia and repeated intraoperatory myocardial biopsies effectuated near 200 patients with heart disease, excluding those with cardiac failure and atrial fibrillation. Using histological histoenzymological and particularly ultrastructural methods, only reversible mitochondrial and sarcoplasmatic reticulum lesions, slight glycogen granules depletions and sporadical dissociation of myofilaments by edema were seen. Major mechanism for the state was suggested: generation of oxygen derived free radicals with consequent oxidative stress and impaired calcium homeostasis. Rare morphological appearance on stunned myocardium was signaled in the references, our collective first made these studies in Romania.
Descriptors: intraoperative period, myocardial ischemia pathology, myocardial stunning pathology, myocardium pathology, acute disease, biopsy, dogs, middle aged, models, animal.

Lall, S.C., K.V. Foyil, S. Sakamoto, R.K. Voeller, J.P. Boineau, R.J.J. Damiano, and R.B. Schuessler (2008). Pulmonary vein isolation and the Cox maze procedure only partially denervate the atrium. Journal of Thoracic and Cardiovascular Surgery 135(4): 894-900.
Abstract: OBJECTIVES: The effects of ablation lines on myocardial innervation and response to autonomic stimuli are unclear. This study examined the effects of radiofrequency ablation on atrial autonomic innervation and compared pulmonary vein isolation and the biatrial Cox maze procedure. METHODS: In 12 acute canines right and left vagosympathetic trunks and right and left stellate ganglia were isolated. Each nerve was stimulated before bipolar ablation, after pulmonary vein isolation, and after the Cox maze procedure. Nadolol (n = 6) and atropine (n = 6) were administered to block sympathetic and parasympathetic responses, respectively. Changes in heart rate and atrioventricular interval were compared. Changes in QRST area relative to an isoelectric baseline (index of local innervation) were calculated. RESULTS: Sympathetic stimulation of each nerve and parasympathetic stimulation of the vagosympathetic trunks caused significant changes in heart rate and atrioventricular interval. After pulmonary vein isolation, the effect of 33% of the nerves on heart rate changes was eliminated. The Cox maze procedure eliminated right stellate sympathetic effects on heart rate. Fifty percent of the nerves caused heart rate changes after the Cox maze procedure. There was no significant effect of either lesion set on atrioventricular interval changes. Stimulation of 50% of nerves after pulmonary vein isolation produced local area changes significantly different from control area. After the Cox maze procedure, a different 50% of the nerves produced local changes different from those seen after pulmonary vein isolation. CONCLUSIONS: Surgical ablation procedures disrupted innervation, affecting heart rate but not atrioventricular interval. Autonomic innervation affecting the atria was changed by pulmonary vein isolation and additionally by the Cox maze procedure. Residual autonomic effects were present even after the complete Cox maze procedure.
Descriptors: atrial fibrillation surgery, cardiac surgical procedures methods, catheter ablation, heart atria innervation, pulmonary veins surgery, dogs, heart atria surgery, models, animal.

Laurent, G., G. Moe, X. Hu, B. Holub, H. Leong Poi, J. Trogadis, K. Connelly, D. Courtman, B.H. Strauss, and P. Dorian (2008). Long chain n-3 polyunsaturated fatty acids reduce atrial vulnerability in a novel canine pacing model. Cardiovascular Research 77(1): 89-97. ISSN: 0008-6363.
NAL Call Number: QM178.A
Abstract: AIM: Our objective was to assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on atrial fibrillation (AF) vulnerability and atrial structure in a new model of atrial cardiomyopathy. METHODS AND RESULTS: Dogs were studied in three groups: seven control dogs (UNPACED) and 24 dogs undergoing simultaneous atrioventricular pacing (for 2 weeks) assigned to placebo treatment (SAVP-PLACEBO, n = 12 dogs) or oral n-3 PUFAs (1 g/day) treatment (SAVP-PUFA, n = 12 dogs). SAVP-PUFA dogs had less AF inducibility (percentage of burst attempts leading to AF episodes: 5.5 +/- 7.4 vs. 20.4 +/- 14.2, P < 0.001) and maintenance [median AF duration: 601 s (377-1216) vs. 1598 s (1195-2400), P < 0.05] than SAVP-PLACEBO dogs. SAVP-PUFA dogs had significantly less local slowing of conduction and conduction heterogeneity than SAVP-PLACEBO dogs. SAVP-PUFA dogs had a significantly smaller increase in atrial matrix metalloproteinase-9 activity and in collagen type I and III messenger RNA expression (in arbitrary units) than SAVP-PLACEBO dogs (0.62 +/- 0.51 vs. 10.80 +/- 5.61, respectively for collagen I, P < 0.05; 1.66 +/- 0.48 vs. 5.24 +/- 1.16, respectively, for collagen III, P < 0.05). CONCLUSION: n-3 PUFA supplementation can reduce AF vulnerability in a new canine pacing model of atrial cardiomyopathy. The mechanism may be related to attenuation of collagen turnover.
Descriptors: atrial fibrillation prevention and control, cardiac pacing, artificial adverse effects, fatty acids, omega 3 pharmacology, atrial natriuretic factor blood, dogs, echocardiography, heart physiopathology, matrix metalloproteinase 9 metabolism, models, animal, myocardium pathology, transforming growth factor beta1 genetics.

Laurita, K.R., R. Katra, B. Wible, X. Wan, and M.H. Koo (2003). Transmural heterogeneity of calcium handling in canine. Circulation Research 92(6): 668-675. ISSN: 0009-7330.
NAL Call Number: RC681.A1A57137
Abstract: Spatial heterogeneity of the action potential and its influence on arrhythmia vulnerability is known. However, heterogeneity of intracellular calcium handling and, in particular, its effect on the electrophysiological substrate is less clear. Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during steady-state baseline pacing and rapid pacing. During baseline pacing, the decay of intracellular calcium to diastolic levels and calcium transient duration were slower (70%, P<0.005) and longer (20%, P<0.005), respectively, closer to the endocardial surface compared with the epicardial surface. Tissue samples isolated from the left ventricular wall demonstrate that sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) expression was significantly less in the subendocardial and midmyocardial layers compared with the subepicardial layer. In contrast, no significant difference in the transmural expression of Na+-Ca2+ exchanger was observed. During rapid pacing, calcium transient altemans and increased levels of diastolic intracellular calcium were significantly greater (P<0.01) closer to the endocardium (101%+-62% and 41%+-15%, respectively) compared with the epicardium (12%+-7% and 12%+-14%, respectively). In conclusion, cells closer to the endocardium exhibit a slower decay of intracellular calcium compared with cells near the epicardium, which may be due in part to reduced expression of SERCA2a. As a possible consequence, calcium transient alternans and increased diastolic levels of intracellular calcium may occur preferentially closer to the endocardial surface.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, arrhythmia, heart disease, electrophysiology, clinical techniques, optical mapping, laboratory techniques, rapid pacing, steady state baseline pacing, clinical techniques, action potential, calcium handling, transmural heterogeneity, calcium transients.

Leach, J.K., E. Patterson, and E.A. O'rear (2004). Encapsulation of a plasminogen activator speeds reperfusion, lessens infarct and reduces blood loss in a canine model of coronary artery thrombosis. Thrombosis and Haemostasis 91(6): 1213-1218. ISSN: 0340-6245.
Abstract: In the present study, a polymer-encapsulated plasminogen activator was investigated as an alternative to restore blood flow more effectively than free plasminogen activator. While current fibrinolytic agents have limited efficacy, attributable to delayed onset of sustained reperfusion and bleeding complications, encapsulated plasminogen activators have shown promise in addressing these shortcomings. A polymer-encapsulated plasminogen activator could offer an effective formulation with a prolonged shelf-life. In this study, coronary artery thrombosis was produced in the anesthetized dog by the injection of thrombin + whole blood, and then one of five randomly selected formulations was administered intravenously: saline, blank microcapsules, free streptokinase (FREE SK), streptokinase and blank microcapsules (FREE SK + BLANK), or streptokinase entrapped in polymer microcapsules (MESK). MESK significantly accelerated the time to reperfusion compared to FREE SK or FREE SK + BLANK. Additionally, substantial reductions were observed in residual clot mass, infarct mass, reocclusion episodes, fibrinogen depletion and blood loss with MESK compared to FREE SK. The results of this study demonstrate that MESK accelerates thrombolysis and the restoration of blood flow compared to identical dosages of FREE SK while also reducing systemic fibrinogenolysis and blood loss. Microencapsulation may produce an improved dosage form for restoring arterial blood flow and reducing bleeding complications with thrombolytic therapy.
Descriptors: cardiovascular system, transport and circulation, pharmacology, coronary artery thrombosis, heart disease, vascular disease, therapy.

Leather, H.A., P. Segers, N. Berends, E. Vandermeersch, and P.F. Wouters (2002). Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Critical Care Medicine. 30(11): 2548-52. ISSN: 0090-3493.
Abstract: OBJECTIVE: Arginine vasopressin is a promising systemic vasopressor in settings such as vasodilatory shock and cardiopulmonary resuscitation. The evidence that arginine vasopressin may also have a pulmonary vasodilatory effect makes it an attractive drug for the treatment of circulatory shock secondary to right ventricular failure and pulmonary hypertension. In the present study, we evaluated the effects of arginine vasopressin on right ventricular function and ventriculovascular coupling in the setting of moderate acute pulmonary hypertension and compared these effects with those of phenylephrine. DESIGN: Prospective laboratory investigation using an established model of acute pulmonary hypertension. SETTING: University hospital laboratory. SUBJECTS: Seven adult beagle dogs weighing 8-14 kg. INTERVENTIONS: After acute instrumentation to measure right ventricular pressure and volume with the conductance technique and pulmonary artery flow and pressure with high-fidelity transducers, the stable thromboxane analogue U46619 was infused continuously to obtain stable pulmonary hypertension. Phenylephrine and arginine vasopressin were administered consecutively in continuous infusions at doses titrated to achieve a 25% increase in aortic pressure. MEASUREMENTS AND MAIN RESULTS: Phenylephrine and arginine vasopressin both increased total pulmonary vascular resistance and arterial elastance without influencing characteristic impedance. Both drugs decreased cardiac output and stroke volume. Right ventricular hydraulic power output was reduced by arginine vasopressin but not by phenylephrine. Most importantly, arginine vasopressin caused a 31% decrease in right ventricular contractility measured as the slope of the preload recruitable stroke work relationship, whereas contractility was preserved during phenylephrine infusion. CONCLUSIONS: In the present model, arginine vasopressin causes pulmonary vascular constriction and exerts an important negative inotropic effect on the right ventricle. These findings suggest that one should be cautious in the use of arginine vasopressin when right ventricular function is compromised.
Descriptors: beagle dogs, adult, arginine vasopressin, pulmonary vascular resistance, pulmonary hypertension.

Lee, B.H., H.W. Seo, and S.E. Yoo (2004). Cardioprotective effects of (2s,3r,4s)-n'-benzyl-n''-cyano-n-(3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2h-benzopyran-4-yl)-guanidine (kr-31372) in rats and dogs. Pharmacology 70(2): 74-82. ISSN: 0031-7012.
NAL Call Number: RM1.P473
Abstract: The cardioprotective effects of (2S,3R,4S)-N'-benzyl-N''-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat hearts subjected to a 30-min global ischemia/30-min reperfusion, KR-31372 (1-10 muM) significantly improved severe contracture (end-diastolic pressure and time to contracture), markedly reduced reperfusion lactate dehydrogenase release, and enhanced the recovery of reperfusion contractile function (left ventricular developed pressure and double product) in a concentration-dependent manner compared with the vehicle-treated group. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, intravenous KR-31372 dose-dependently reduced infarct size from 58.6% to 48.5, 48.1 and 39.6% at 0.3, 1.0 and 3.0 mg/kg, respectively (p<0.05). In anesthetized beagle dogs that underwent a 1.5-hour occlusion followed by a 5-hour reperfusion, KR-31372 (2 mg/kg, i.v.) markedly reduced infarct size from 57.0% in controls to 28.0% (p<0.05). The cardioprotective effects of KR-31372 on contractile function in globally ischemic rat hearts and on reperfusion injury in anesthetized rats were significantly reversed by pretreatment with selective adenosine triphosphate-sensitive potassium (KATP) channel blockers, sodium 5-hydroxydecanoate and glibenclamide. Taken together, these results indicate that KR-31372 possesses potent cardioprotective effects in rats and dogs and its effects may be mediated by activation of mitochondrial KATP channels.
Descriptors: cardiovascular system, transport and circulation, pharmacology, ischemia, reperfusion injury, vascular disease, drug therapy, pathology, cardioprotection, double product, end diastolic pressure, left ventricular developed pressure, severe contracture.

Lee, C.H., J.M. Goo, K.T. Bae, H.J. Lee, K.G. Kim, E.J. Chun, C.M. Park, and J.G. Im (2007). CTA contrast enhancement of the aorta and pulmonary artery: the effect of saline chase injected at two different rates in a canine experimental model. Investigative Radiology 42(7): 486-90. ISSN: 0020-9996.
Abstract: OBJECTIVE: To investigate the effect of saline chase injected at 2 different rates on computed tomography (CT) angiography. MATERIALS AND METHODS: This study was approved by our institutional animal study committee. Three injection protocols were used; contrast injection (24 mL, 0.8 mL/s) without saline chase (protocol A), contrast injection with saline chase injected at the same rate as the contrast medium (protocol B), and contrast injection with saline chase injected at half the rate (0.4 mL/s) of the contrast medium (protocol C). In the 3 dogs used in our study, each of the protocols was applied twice for every dog resulting in a total of 18 sessions of monitoring scans. CT images were acquired every second at the fixed level of the aorta and pulmonary artery (PA). The duration of plateau, plateau deviation, and peak arterial enhancement were computed and compared using the Kruskall-Wallis and Mann-Whitney U test. RESULTS: Peak contrast enhancements were significantly more delayed with protocol B than with protocol A in both the PA (B: 48 seconds, A: 30 seconds, P=0.024) and aorta (B: 46 seconds, A: 38 seconds, P=0.024). The duration of enhancement plateau was longer with protocol B than with protocol A in PA (B: 14.8 seconds, A: 9.0 seconds, P=0.002) and in aorta (B: 16.2 seconds, A: 11.6 seconds, P=0.004). Protocol C had the longest duration of plateau in both PA (34.5 seconds, P=0.002) and aorta (33.8 seconds, P=0.004) with uniform plateau enhancement. The peak enhancement values of protocol C, however, were substantially lower than that of protocol A and B in both the PA (A: 262 HU, B: 239 HU, C: 191 HU, P=0.001) and aorta (A: 263 HU, B: 268 HU, C: 210 HU, P=0.001). CONCLUSIONS: Saline chase prolongs the duration of plateau and delays peak enhancement of the pulmonary artery and aorta. Saline chase injected at half the rate of contrast medium injection allowed more uniform and prolonged plateau contrast enhancement than other protocols.
Descriptors: angiography instrumentation, aorta physiology, contrast media, pulmonary artery physiology, sodium chloride administration and dosage, tomography, x ray computed instrumentation, aorta pathology, dogs, models, animal, pulmonary artery pathology.

Lee, T.M., M.S. Lin, T.F. Chou, C.H. Tsai, and N.C. Chang (2004). Adjunctive 17beta-estradiol administration reduces infarct size by altered expression of canine myocardial connexin43 protein. Cardiovascular Research 63(1): 109-117. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Descriptors: cardiovascular system, transport and circulation, endocrine system, chemical coordination and homeostasis, pharmacology, coronary occlusion, heart disease, ischemia, vascular disease, ischemia reperfusion injury, myocardial infarction, western blot, genetic techniques, confocal microscopy, imaging and microscopy techniques, lucigenin derived chemiluminescence, laboratory techniques, infarct size.

Letsou, G.V., E.M. Breznock, J. Whitehair, R.S. Kurtz, R. Jacobs, M.L. Leavitt, H. Sternberg, S. Shermer, S. Kehrer, J.M. Segall, M.A. Voelker, H.D. Waitz, and P.E. Segall (2003). Resuscitating hypothermic dogs after 2 hours of circulatory arrest below 6degreec. Journal of Trauma Injury Infection and Critical Care 54(5 Supplement): S177-S182. ISSN: 1079-6061.
Abstract: Background: Ultraprofound hypothermia may have a place in trauma rescue and resuscitation. We describe resuscitation of dogs after asanguineous perfusion and circulatory arrest of 2 hours at 2degree to 4degreeC. Methods: Nine dogs were cooled using a bypass apparatus and their circulating blood replaced with bicarbonated Hextend (Abbott, North Chicago, IL). Perfusion was continued to 2degree to 4degreeC, and 60 mL of 2 mol/L KCl and 20 mL of 50% MgSO4cntdot7H2O were infused intra-arterially, and circulation was arrested for 2 hours. The dogs were then rewarmed, transfused, defibrillated, weaned from by-pass, and allowed to awaken. Preoperative and postoperative biochemistry and hematology were compared. Results: Six dogs recovered fully. One of these dogs died of an infection 2 weeks later. Three other dogs never recovered because of technical or procedural difficulties. Biochemical and hematologic parameters were normal by 3 weeks. Conclusion: Hypothermic blood substitution with Hextend allows resuscitation after 2 hours of ice-cold circulatory arrest in dogs.
Descriptors: biochemistry and molecular biophysics, blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, methods and techniques, circulatory arrest, vascular disease, resuscitation, clinical techniques, therapeutic and prophylactic techniques, hypothermia.

Li Ying Qian , Yang Xiao Yan , Zhou Shun Chang , and Gong Pei Li (2003). Effects of phenolic alkaloids of menispermum dauricum on the hemodynamics and coronary circulation in anesthetized dog. Yaoxue Xuebao 38(9): 658-660. ISSN: 0513-4870.
Abstract: Aim: To observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD) on the hemodynamics, coronary circulation and oxygen metabolism of the myocardium in anesthetized dogs. Methods: In this study, the changes of LVSP, LVEDP and +-dp/dtmax, the flow of coronary artery and myocardial energy metabolism were measured in anesthetized dog with PAMD or NS. Results: In the anesthetized dogs, compared with pre-treatment status, PAMD at 3.5 and 7.0 mgcntdotkg-1 caused decreases in the left ventricular systolic pressure(LVSP), +-dp/dtmax, heart rate, the rate of oxygen utilization, the coronary and general peripheral resistance. It was found to increase myocardial oxygen and coronary flow. There were no significant change in the left ventricular end diastolic pressure (LVEDP). Conclusion: PAMD can ameliorate hemodynamics, coronary circulation and myocardial metabolism.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, coronary resistance, general peripheral resistance, heart rate, hemodynamics, left ventricular systolic pressure.
Language of Text: Chinese.

Ling, L.H., C.A. Moreno, T. Lombari, and C.P. Appleton (2003). Flow propagation velocity is load dependent: evidence from an open-chest dog model. Circulation 108(17 Supplement): IV-393. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, aortic occlusion, vascular disease, balloon aortic occlusion, experimental surgical techniques, laboratory techniques, echocardiography, clinical techniques, diagnostic techniques, right atrial pacing, clinical techniques, therapeutic and prophylactic techniques, lv diastolic dimension [left ventricular diastolic dimension], lv systolic dimension [left ventricular systolic dimension], cardiac output, ejection fraction wall stress, flow propagation velocity, load dependence, mean left atrial pressure, transmitral driving pressure

Liu, J.C., P.K. Kao, P. Chan, Y.H. Hsu, C.C. Hou, G.S. Lien, M.H. Hsieh, Y.J. Chen, and J.T. Cheng (2003). Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacology 67(1): 14-20. ISSN: 0031-7012.
NAL Call Number: RM1.P473
Abstract: Stevioside is a sweet-tasting glycoside isolated from the leaves of Stevia rebaudiana. It has been used as a noncaloric sugar substitute in Japan and Brazil for decades. Previous studies have shown that it lowered blood pressure in spontaneously hypertensive rats by intravenous injection. This study was designed to evaluate the hypotensive effect of stevioside in dogs and to define the underlying mechanism. After nasogastric administration of stevioside powder (200 mg/kg), the blood pressure of healthy mongrel dogs began to significantly decrease at 60 min and returned to baseline level at 180 min. The reduction of blood pressure was more rapid (at 5-10 min) and effective after intravenous injection. However, no significant change of blood pressure was noted after injection through left vertebral artery, implicating that the hypotensive effect is not related to the central nervous system. Stevioside also showed significant hypotensive effects in renal hypertensive dogs, in a dose-dependent manner. In cultured rat aortic smooth muscle cells (A7r5 cell line), stevioside can dose-dependently inhibit the stimulatory effects of vasopressin and phenylephrine on intracellular Ca2+ in a calcium-containing medium. However, no intracellular Ca2+ inhibitory effect was observed in calcium-free medium, implicating that stevioside may inhibit the Ca2+ influx from extracellular fluid. Our present data show that stevioside did not influence the calcium ionophore (A23187) induced Ca2+ influx, indicating that the antagonistic effect was through Ca2+ channels. This study confirmed that stevioside is an effective antihypertensive natural product, and its hypotensive mechanism may be probably due to inhibition of the Ca2+ influx.
Descriptors: cardiovascular system, transport and circulation, pharmacology, hypertension, vascular disease, drug therapy, hypotension, drug therapy, blood pressure, calcium ion influx.

Loh, P., S.Y. Ho, T. Kawara, R.N.W. Hauer, M.J. Janse, G. Breithardt, and J.M.T. De Bakker (2003). Reentrant circuits in the canine atrioventricular node during atrial and ventricular echoes: electrophysiological and histological correlation. Circulation 108(2): 231-238. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background: The anatomic-electrophysiological correlation of AV nodal reentry is unclear. To localize reentrant circuits during atrial and ventricular echoes and to characterize sites of slow conduction and block, we correlated histology with electrophysiology of the AV node. Methods and Results: In 10 isolated dog hearts, extracellular electrical activity was recorded in Koch's triangle at 208 or 247 sites (interelectrode distance, 0.5 and 0.3 mm) after removal of 0.7 to 1.5 mm of overlying atrial tissue. Resection did not affect refractory periods. Five hearts were subjected to histology. Complete atrial echoes were induced in 1 heart, incomplete atrial echoes in 5 hearts. Unidirectional conduction block occurred at the atrial-transitional cell junction in the superior area. Zones of slow conduction arose at the atrial-transitional or the transitional-compact node junction in the inferior area. Complete reentrant circuits of ventricular echoes were obtained in 5 hearts. Unidirectional conduction block occurred at the compact node-transitional cell junction in the superior area. Localized zones of slow conduction arose at the junctions between the different types of tissue in the inferior area. Conclusions: In the dog heart, tissue architecture and functional dissociation between the inferior and the superior region of the AV node enable dual physiology and reentry. Slow conduction and functional conduction block occur at the junctions between the different types of tissue in the AV nodal area. Atrial echoes were enabled by conduction block at the atrial-transitional cell junction, whereas during ventricular echoes conduction block occurred at the compact node-transitional cell junction.
Descriptors: cardiovascular medicine, human medicine, medical sciences, electrophysiology, clinical techniques, histology, histology and cytology techniques, laboratory techniques, atrial echo, atrial transitional cell junction, atrioventricular nodal reentry, anatomic electrophysiological correlation, extracellular electrical activity, inferior area, mapping, slow conduction, block sites, superior area, transitional compact node junction, unidirectional conduction block, ventricular echo.

Lucats, L., L. Vinet, A. Bize, X. Monnet, D. Morin, J.B. Su, P. Rouet Benzineb, O. Cazorla, J.J. Mercadier, L. Hittinger, A. Berdeaux, and B. Ghaleh (2007). The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. Cardiovascular Research 73(3): 560-7. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bize, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh. OBJECTIVES: Late preconditioning reduces contractile dysfunction during myocardial stunning. Mechanisms involving adaptation of calcium handling during excitation-contraction coupling to late preconditioning remain to be established. Thus, we investigated whether the late preconditioned myocardium is associated with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2) and its regulatory protein FKBP12.6. METHODS: Chronically instrumented conscious dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10-min coronary artery occlusion followed by reperfusion. They were studied 24 h later in the late preconditioned state (day 1). RESULTS: Maximal velocity of wall thickening at day 1 was increased as compared to corresponding baseline at day 0 (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg) induced a dose-dependent decrease in wall thickening. In the late preconditioned state, this negative inotropic response was significantly reduced vs. control state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase after late preconditioning as compared to the control state. The amount of RyR2 and its phosphorylated state were similar and binding experiments did not reveal any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and phospholamban levels were not altered by late preconditioning. CONCLUSIONS: The late preconditioned myocardium is characterized by an adaptation of regional function associated with an increased expression of FKBP12.6. This demonstrates an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.
Descriptors: ischemic preconditioning, myocardial, myocardial stunning metabolism, myocardium metabolism, tacrolimus binding proteins metabolism, binding sites, blotting, western methods, calcium metabolism, dogs, dose response relationship, drug, echocardiography, models, animal, myocardial contraction, myocardial reperfusion, myocardial stunning pathology, myocardial stunning physiopathology, myocardium pathology, protein binding, ryanodine pharmacology, ryanodine receptor calcium release channel analysis, ryanodine receptor calcium release channel metabolism, sarcoplasmic reticulum metabolism, tacrolimus binding proteins analysis, time factors.

Lynch, J.E., A. Pouch, R. Sanders, M. Hinders, K. Rudd, and J. Sevick (2007). Gaseous microemboli sizing in extracorporeal circuits using ultrasound backscatter. Ultrasound in Medicine and Biology 33(10): 1661-75. ISSN: 0301-5629.
NAL Call Number: QC244.U4
Abstract: This paper describes efforts to estimate the size of gaseous microemboli (GME) in extracorporeal blood circuits based on the amplitude of backscattered ultrasound, starting with analytic modeling of the scattering behavior of GME in blood. After neglecting resonance effects, this model predicts a linear relationship between the amplitude of backscattered echoes and the diameter of GME. Computer simulations based on the cylindrical acoustic finite integration technique were performed to test some of the simplifying assumptions of the analytical model, with the simulations predicting small deviations from the linear approximation that could be treated as random scatter. Ultrasonic and microscopic measurements of injected GME were then performed on a test circuit to determine the linear correlation coefficient between echo amplitude and GME diameter in conditions like those employed in real cardiopulmonary bypass (CPB) circuits. The correlation coefficient determined through this study was further validated in a closed-loop CPB circuit using canine blood. This study shows that the amplitude of ultrasonic backscattered echoes can be used to accurately estimate the size distribution of a population of detected GME when the spacing of emboli is great enough to minimize interference and other multi-path scattering effects. With the high flow rates found in CPB circuits, typically ranging from 2 to 6 L per minute (equivalent to a flow velocity of 0.3 to 1 m/s through the circuit tubing), this assumption will be valid even when hundreds of emboli per second pass through the circuit. Therefore, sizing of GME using the ultrasonic backscatter models described in this paper is a viable method for estimating embolic load delivered to a patient during a CPB procedure.
Descriptors: computer simulation, embolism, air ultrasonography, extracorporeal circulation adverse effects, image interpretation, computer assisted, algorithms, cardiopulmonary bypass adverse effects, dogs, models, animal, scattering, radiation, ultrasonics.

Maalej, N. and J.D. Folts (1996). Effect of shear stress on acute thrombus formation in stenosed dog carotid arteries. FASEB Journal 10(3): A565. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, nervous system, neural coordination, adhesion, aggregation, atherosclerosis, meeting abstract, myocardial infarction, platelet activation, stroke.

Mahmoudabady, M., M. Mathieu, L. Dewachter, I. Hadad, L. Ray, P. Jespers, S. Brimioulle, R. Naeije, and K. McEntee (2008). Activin-A, transforming growth factor-beta, and myostatin signaling pathway in experimental dilated cardiomyopathy. Journal of Cardiac Failure 14(8): 703-9.
NAL Call Number: RC685.C173
Abstract: BACKGROUND: The pathogenic mechanisms of dilated cardiomyopathy are still uncertain. A number of cytokines and growth factors participate in the remodeling process of the disease. METHODS: We investigated the cardiac myostatin, transforming growth factor (TGF)beta, and activin-A/Smad growth inhibitory signaling pathway in experimental dilated cardiomyopathy. Transvenous endomyocardial biopsies of the interventricular septum were taken weekly in 15 beagle dogs during the development of heart failure (HF) induced by rapid pacing over a period of 7 weeks. Genes involved in the myostatin-TGFbeta-activin-A/Smad signaling pathway and the cardiac hypertrophic process were quantified by real-time quantitative polymerase chain reaction. Left ventricular volume, function, and mass were evaluated by echocardiography. RESULTS: Overpacing was associated with increased left ventricular volumes and decreased ejection fraction, whereas the left ventricular mass remained unchanged. TGFbeta was increased in moderate HF. Activin-A mRNA expression was 4-fold higher in overt congestive HF than at baseline. A 2-fold decrease of activin type II receptors and activin receptor interacting protein 2 gene expressions were observed, as well as a transient decrease of follistatin. Activin type I receptors, activin receptor interacting protein 1, follistatin-related gene, and myostatin remained unchanged. The inhibitory Smad 7, a negative feedback loop regulator of the Smad pathway, was overexpressed in severe HF. Gene expression of the cyclin-dependent kinase inhibitor p21, a direct target gene of the Smad pathway, was 8-fold up-regulated in HF, whereas cyclin D1 was down-regulated. CONCLUSION: We conclude that tachycardia-induced dilated cardiomyopathy is characterized by gene overexpression of the TGFbeta-activin-A/Smad signaling pathway and their target gene p21 and by the absence of ventricular hypertrophy.
Descriptors: activins metabolism, cardiomyopathy, dilated metabolism, cyclin d1 metabolism, cyclin dependent kinase inhibitor p21 metabolism, myostatin metabolism, signal transduction, cardiomyopathy, dilated genetics, cardiomyopathy, dilated ultrasonography, cytokines metabolism, disease progression, dogs, gene expression, intercellular signaling peptides and proteins metabolism, models, animal.

Mangrum, J.M., T.H.I. Everett, L.C. Kok, L. Shang, and D.E. Haines (1999). Atrial mechanoelectric feedback in a chronic dog model: stretch dominates stress in atrial fibrillation vulnerability. Circulation 100(18 SUPPL.): I.341. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, atrial fibrillation, heart disease, vulnerability, atrial mechanoelectric feedback, atrial stretch, atrial wall stress, meeting abstract.

Markos, F., B.A. Hennessy, M. Fitzpatrick, J. O'sullivan, and H.M. Snow (2002). The effect of tezosentan, a non-selective endothelin receptor antagonist, on shear stress-induced changes in arterial diameter of the anaesthetized dog. Journal of Physiology 544(3): 913-918. ISSN: 0022-3751.
NAL Call Number: 447.8 J82
Abstract: The effects of changes in the mean (Sm) and pulsatile (Sp) components of arterial wall shear stress on arterial dilatation of the iliac artery of the anaesthetized dog were examined in the absence and presence of the endothelin receptor antagonist tezosentan (10 mg kg-1 I.V.; Ro 61-0612; (5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide)). Changes in shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and stimulation of the left ansa subclavia. An increase in Sm from 1.81+-0.3 to 7.29+-0.7 N m-2 (means+-S.E.M.) before tezosentan caused an endothelium-dependent arterial dilatation which was unaffected by administration of tezosentan for a similar increase in Sm from 1.34+-0.6 to 5.76+-1.4 N m-2 (means+-S.E.M.). In contrast, increasing the Sp from 7.1+-0.8 to a maximum of 11.5+-1.1 N m-2 (means+-S.E.M.) before tezosentan reduced arterial diameter significantly. Importantly, after administration of tezosentan subsequent increases in Sp caused arterial dilatation for the same increase in Sp achieved prior to tezosentan, increasing from a baseline of 4.23+-0.4 to a maximum of 9.03+-0.9 N m-2 (means+-S.E.M.; P<0.001). In conclusion, the results of this study provide the first in vivo evidence that pulsatile shear stress is a stimulus for the release of endothelin from the vascular endothelium.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, arterial diameter, arterial dilatation, arterial wall shear stress, pulsatile components, endothelium dependent arterial dilatation, shear stress induced changes, stroke volume.

Markos, F., B.A. Hennessy, M. Fitzpatrick, J. O'sullivan, and H.M. Snow (2002). Reverse arterial wall shear stress causes nitric oxide-dependent vasodilatation in the anaesthetised dog. Pfluegers Archiv European Journal of Physiology 445(1): 51-54. ISSN: 0031-6768.
Abstract: The effects of a maintained increase in mean arterial wall shear stress (SSm) caused by blood flow in the normal and reverse direction on dilatation of the iliac artery were examined in the anaesthetised dog. Blood flow in the left iliac artery was varied in both the forwards and reverse directions by a perfusion pump connecting the right and left femoral arteries. An increase in blood flow, and therefore SSm in either direction, caused an increase in arterial diameter. However, an increase in forwards SSm (control 4.1+-0.11 mm) caused a significantly greater change in arterial diameter than an equivalent increase in the reverse direction (control 4.3+-0.08), 0.198+-0.02 mm vs. 0.132+-0.02 mm (mean+-SEM) respectively, for the same increase in SSm (3.23 N/m2). The increase in arterial diameter in response to an increase in forwards or reverse SSm was attenuated by L-NAME (80 mg/kg i.v.), indicating that the arterial dilatation was mediated by nitric oxide (NO). These findings confirm that endothelial NO release is dependent on the steady-state SSm and that the response occurs irrespective of the direction in which this force is applied, but is attenuated in the reverse direction.
Descriptors: cardiovascular system, transport and circulation, veterinary medicine, medical sciences, anesthesia, clinical techniques, shear stress, vasodilatation.

Masugata, H., B. Peters, S. Lafitte, B. Yao, M. Strachan, O.L. Kwan, K. Ohmori, K. Mizushige, and M. Kohno (2003). Comparison of open- and closed-chest canine model for quantification of coronary stenosis severity by myocardial contrast echocardiography. Investigative Radiology 38(1): 44-50. ISSN: 0020-9996.
Abstract: RATIONALE AND OBJECTIVES: The objective of the present study was to compare the data regarding the ability of real-time myocardial contrast echocardiography (MCE) to assess altered myocardial blood flow produced by graded coronary stenoses between open- and closed-chest canine models. MATERIALS AND METHODS: Three grades of left anterior descending coronary artery stenosis and occlusion were created in 6 open- and 6 closed-chest canine models. MCE used FS-069 infusion and real-time imaging. Myocardial signal intensity versus time plots were fitted to a 1-exponential function to obtain the peak signal intensity (A) and rate of signal intensity rise (b) for quantification of myocardial blood flow. RESULTS: The value of b obtained from closed-chest canine models (without stenosis=0.995+-0.087, mild stenosis=0.968+-0.076, moderate stenosis=0.569+-0.077, severe stenosis=0.288+-0.032, occlusion=0.085+-0.031) was not significantly different from that obtained from open-chest canine models (without stenosis=1.028+-0.107, mild stenosis=0.998+-0.098, moderate stenosis=0.601+-0.055, severe stenosis=0.321+-0.029, occlusion=0.079+-0.028) at any grade of stenosis (P=0.09, 0.08, 0.44, 0.11, 0.74, respectively). CONCLUSIONS: In myocardial regions where attenuation of the ultrasound beam and artifacts produced by the chest wall are minimal, the data from transthoracic MCE in the closed-chest model may show values similar to those from MCE in the open-chest model.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, coronary stenosis, heart disease, vascular disease, diagnosis, closed chest model, laboratory techniques, myocardial contrast echocardiography, clinical techniques, diagnostic techniques, open chest model, laboratory techniques, peak signal intensity, signal intensity.

Mc Entee, K., C. Clercx, H. Amory, C. Michaux, J.J. Dardenne, D. Soyeur, and M. Henroteaux (1999). Doppler echocardiographic study of left and right ventricular function during dobutamine stress testing in conscious healthy dogs. American Journal of Veterinary Research 60(7): 865-871. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: Objective-To evaluate left and right ventricular filling and ejection performances by use of Doppler echocardiography in healthy, conscious dogs submitted to dobutamine stress testing. Animals-10 unsedated, healthy adult Beagles. Procedure-Doppler echocardiography was performed during cardiac stress testing on each dog twice at 24-hour intervals. Dobutamine was infused in 10 mug/kg of body weight/min incremental dosages, from 12.5 to 42.5 mug/kg/min. Duration of each step was 15 minutes. Doppler measurements were recorded at baseline and at each stage of dobutamine infusion, whereas aortic diameter was measured at baseline and at peak dosage by use of two-dimensional echocardiography. Results-Dobutamine infusion induced a significant increase in velocity time integrals and in peak flow velocities at the aortic, pulmonic, mitral, and tricuspid valves. Acceleration time-to-deceleration time ratio at the aortic wave also was increased significantly. On the other hand, ejection time, acceleration time, and deceleration time at the aortic and pulmonic valves and peak flow velocity of the E wave-to-peak flow velocity of the A wave ratio at the mitral and tricuspid valves decreased significantly during the test. The acceleration time-to-deceleration time ratio at the pulmonic wave was unchanged. A significant, progressive increase in cardiac index also was observed during dobutamine infusion, with a maximal increase of 104% from baseline. This was mediated initially by an increase in stroke index and, at higher dosages, by an increase in heart rate. Conclusions and Clinical Relevance-Doppler echocardiography performed during dobutamine stress testing may be a reliable method of assessing myocardial function in dogs with cardiovascular disease.
Descriptors: cardiovascular system, transport and circulation, radiology, medical sciences, veterinary medicine, medical sciences, dobutamine stress testing, evaluation method, doppler echocardiography, imaging method, myocardial function, assessment, left ventricular, right ventricular.

Mc Entee, K., C. Clercx, D. Soyeur, H. Amory, C. Michaux, T. Flandre, E. Jonville, C. Pynnaert, N. Miserque, and M. Henroteaux (2001). Usefulness of dobutamine stress tests for detection of cardiac abnormalities in dogs with experimentally induced early left ventricular dysfunction. American Journal of Veterinary Research 62(3): 448-455. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: Objective: To determine whether dobutamine stress tests (DST) can be used to detect cardiac dysfunction in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). Animals: 7 adult male Beagles. Procedure: A pacemaker was surgically implanted in each dog at the level of the right ventricular apex. Electrocardiography, Doppler sphygmomanometry, and Doppler echocardiography were performed before and during a DST prior to activation of the pacemaker and every 3 to 4 days during the period of RRVP. Dobutamine stress tests were performed by infusing dobutamine at incremental dosages ranging from 12.5 to 42.5 mug/kg of body weight/min. Results: Clinical signs of congestive heart failure were not observed during the pacing period. However, all dogs developed ELVD associated with significant changes in values for most Doppler echocardiographic variables obtained prior to DST. Adverse cardiac effects were not detected during DST. Most Doppler echocardiographic indices of cardiac function were significantly altered in response to dobutamine infusion during the pacing period, compared with prepacing values. However, a dobutamine-induced 2-fold increase in cardiac output was maintained. Conclusions and Clinical Relevance: Dobutamine stress tests can be safely performed in dogs with experimentally induced ELVD. Dobutamine stress tests may be a sensitive, noninvasive diagnostic method, complementary to standard clinical examinations, for detection of early cardiac dysfunction in dogs asymptomatic for dilated cardiomyopathy.
Descriptors: veterinary medicine, medical sciences, methods and techniques, pharmacology, cardiovascular system, transport and circulation, cardiac abnormalities, heart disease, dilated cardiomyopathy, left ventricular dysfunction, experimentally induced early disease model, dobutamine stress test, detection method, diagnostic method.

Mehta, A., A.C. Jain, and M.C. Mehta (2003). Electrocardiographic effects of intravenous cocaine: an experimental study in a canine model. Journal of Cardiovascular Pharmacology 41(1): 25-30. ISSN: 0160-2446.
Abstract: Cocaine abuse causes cardiac dysfunction. Acute intravenous administration of cocaine may lead to development of severe arrhythmias, conduction abnormalities, ST-T changes, and sudden death. Understanding arrhythmogenesis due to cocaine may provide a therapeutic approach to reduce morbidity and mortality. We studied the arrhythmogenic activity and other electrocardiographic abnormalities resulting from an intravenous bolus of cocaine. Baseline and postanesthetic electrocardiographic findings were compared with those after administration of intravenous bolus of various doses of cocaine hydrochloride in 20 dogs. The study was done in three phases (phase I: low dose of cocaine (1 mg/kg, 15 experiments); phase II: medium dose (2 mg/kg, 30 experiments); and phase III: high dose (5-7 mg/kg, 10 experiments)). Plasma levels of cocaine were estimated. The low dose induced sinus bradycardia, sinus arrhythmia, atrial ectopic, wandering pacemaker, unifocal ventricular premature contractions, and ventricular couplets. The medium dose generated moderately severe arrhythmias that were of supraventricular origin. Atrial flutter and atrial fibrillation were observed in two experiments each. Ventricular arrhythmias were manifested as unifocal, multifocal, interpolated ventricular premature contractions as well as bigeminy, trigeminy, couplets, and salvos. The high dose of 5-7 mg/kg increased electrocardiographic intervals and caused ST-segment elevation as well as serious life-threatening arrhythmias. Three of the dogs developed sustained ventricular tachycardia followed by ventricular flutter-fibrillation and death.
Descriptors: behavior, cardiovascular system, transport and circulation, toxicology, atrial ectopic, heart disease, atrial fibrillation, heart disease, atrial flutter, heart disease, cardiac arrhythmia, drug abuse, behavioral and mental disorders, sinus arrhythmia, sinus bradycardia, ventricular tachycardia, st changes, unifocal ventricular premature contractions, ventricular couplets, wandering pacemaker.

Miao, C.H., H. Jiang, and B. Sun (1997). Inhaled nitric oxide improves ventilation efficiency and hemodynamic properties in dogs with endotoxin induced acute respiratory distress syndrome. Pediatric Research 41(4 PART 2): 36A ISSN: 0031-3998.
NAL Call Number: RJ1.P4
Descriptors: blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, pharmacology, respiratory system, respiration, toxicology, cardiovascular drug, critical care, endotoxin induced acute respiratory distress syndrome, gas exchange, hemodynamic properties, inhaled administration efficacy, nitric oxide, pharmacodynamics, pharmacokinetics, pharmacology, respiratory system, respiratory system disease, ventilation efficiency.

Milei J , Beigelman R , Valero E , Pesce R , Quel E , Armentano R , and Storino R (1990). Histological features of the canine myocardium surrounding the laser beam crater. Archivos Del Instituto De Cardiologia De Mexico 60(1): 21-26. ISSN: 0020-3785.
Abstract: Laser beam constitutes a potential therapy in modern cardiology. Although its myocardial effects are known, they have been insufficiently evaluated at the surviving myocytes zone surrounding the evaporated crater. In order to assess myocyte cellular and organellar damage, we studied 8 isolated canine hearts radiated with different intensities by a CO2He laser beam 2.4, 3.5, 5, 15, 25, 30 and 40 Watts, varying the exposition time from 1 to 6 sec. Color photographs from the post-radiated lesions on front and depth were obtained. Their volumes were measured applying the cylinder and the cut out-conus formulas according to the shape of the lesions and then the involved tissues were embedded in paraffin for histological studies. Previously, samples of the lesions were fixed in glutaraldehyde for ultrastructural studies. Volumes of the craters wre from 0.0004 to 19.57 mm3. Three layers were observed: (a) a carbonized internallining which measured x 15 micrones in thickness; (b) a coagulation necrotic zone ("gruyere cheese-like"), 70 microns thickness; (c) finally more peripherally, a layer consisting of myocytes with patchy homogeneous cytoplasm, and scarse positivity for the Barbeito Lopex Trichome Stain (a positive technique in cases of myocardial damage). Ultrastructurally, crater peripheral cells showed cytosol and mitochondrial edema without membrane disruptions. These findings suggest that myocytes surrounding the laser beam crater, show reversible lesions. Therefore laser beam appears a safe procedure to be used in myocardium.
Descriptors: cardiovascular system, transport and circulation, cell biology, pathology, radiation biology, organelle damage myocyte cellular assessment laser therapy effects safe procedure.
Language of Text: Spanish.

Monaco, B.A., A. Benicio, I.S. Contreras, L.E. Mingrone, G. Ballester, and L.F. Moreira (2007). Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach. Arquivos Brasileiros De Cardiologia 88(3): 291-6.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.
Descriptors: aorta, thoracic surgery, evoked potentials, somatosensory physiology, ischemic preconditioning standards, spinal cord ischemia diagnosis, spinal cord ischemia prevention and control, analysis of variance, dogs, ischemic preconditioning methods, models, animal, monitoring, intraoperative methods, paraplegia etiology, reperfusion methods, sensitivity and specificity, spinal cord blood supply, spinal cord physiopathology, spinal cord ischemia etiology, spinal cord ischemia physiopathology, statistics, nonparametric, time factors, vascular surgical procedures adverse effects.
Language of Text: Portuguese.

Monahan, T.S., N.D. Andersen, H. Panossian, J.A. Kalish, S. Daniel, G.V. Shrikhande, C. Ferran, and F.W. Logerfo (2007). A novel function for cadherin 11/osteoblast-cadherin in vascular smooth muscle cells: modulation of cell migration and proliferation. Journal of Vascular Surgery Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 45(3): 581-9. ISSN: 0741-5214.
Abstract: OBJECTIVE: Intimal hyperplasia is a common cause of vein graft failure in cardiovascular surgery. The molecular basis for intimal hyperplasia remains poorly defined. We have previously identified, by gene chip analysis of vein grafts, increased messenger (mRNA) for the adhesion molecule cadherin 11/osteoblast-cadherin (CDH11). The function of CDH11 in vascular cells is unknown. The aim of the present study is to confirm CDH11 expression in vein grafts and characterize its role in vascular remodeling. METHODS: Cephalic vein interposition grafts were implanted in a canine model and harvested at predetermined time points. CDH11 protein expression was determined by immunohistochemistry. Early passage human coronary artery smooth muscle cells (SMCs) were used for in vitro studies. Real-time polymerase chain reaction was used to assess cellular CDH11 mRNA levels. CDH11 signaling was inhibited by either transfection with silencing RNA targeting CDH11 or with a blocking antibody to CDH11. Cellular migration was evaluated and cellular proliferation was assessed. RESULTS: Expression of CDH11 was increased in medial SMCs of vein grafts recovered at 7, 14, and 30 days after surgery compared with control veins from the same animals. In vitro CDH11 mRNA was up-regulated 1.8 +/- 0.2-fold (P = .003) in SMCs after treatment with tumor necrosis factor-alpha. Cellular migration was attenuated by inhibition of CDH11 both with a blocking antibody (0.67 +/- 0.09; P = .063) and gene knockdown mediated by small interfering RNA (0.67 +/- 0.14; P = .036). SMC proliferation decreased by 3.1-fold (P = .006) in the presence of CDH11-blocking antibody. Knockdown of CDH11 mediated by small interfering RNA resulted in a 1.3-fold (P = .018) decrease in proliferation. CONCLUSIONS: CDH11 is up-regulated in SMC in vivo and in vitro as part of the response to injury. Inhibition of CDH11 decreases SMC migration and proliferation, two pathogenic effectors of intimal hyperplasia.
Descriptors: cadherins biosynthesis, cell movement, cell proliferation, muscle, smooth, vascular metabolism, myocytes, smooth muscle metabolism, anastomosis, surgical, antibodies pharmacology, cadherins genetics, cadherins immunology, cell cycle drug effects, cells, cultured, coronary vessels metabolism, coronary vessels physiopathology, dogs, femoral artery surgery, hyperplasia, models, animal, muscle, smooth, vascular drug effects, muscle, smooth, vascular pathology, muscle, smooth, vascular physiopathology, myocytes, smooth muscle drug effects, myocytes, smooth muscle pathology, rna interference, rna, messenger metabolism, rna, small interfering metabolism, time factors, tumor necrosis factor alpha pharmacology, up regulation, veins metabolism, veins physiopathology, veins transplantation.

Mori, E., H. Ikeda, N. Haramaki, T. Ueno, and T. Imaizumi (1997). Oxidative stress due to no-peroxynitrite pathway is involved in a canine model of myocardial stunning. Journal of the American College of Cardiology 29(2 SUPPL. A): 129A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, animal model, d arginine, ischemia, l arginine, lipid peroxidation marker, malondialdehyde, myocardial stunning, nitric oxide peroxynitrite pathway, nitrotyrosine, oxidative stress, vascular disease.

Morita, H., D.P. Zipes, S.T. Morita, and J. Wu (2007). Mechanism of U wave and polymorphic ventricular tachycardia in a canine tissue model of Andersen-Tawil syndrome. Cardiovascular Research 75(3): 510-8. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: OBJECTIVE: Andersen-Tawil syndrome (ATS) is a channelopathy affecting inward rectifier potassium I(K1) with QT prolongation, large U waves, and frequent ventricular tachycardia (VT). Although ATS is clinically defined and genetically identified, its electrophysiological mechanism is still unclear, and thus, was the subject of the current study. METHODS AND RESULTS: We replicated the major electrophysiological features of ATS with cesium chloride (CsCl, at I(K1) blockade concentration of 5-10 mmol/l) in 23 isolated canine left ventricular tissues perfused arterially with Tyrode's solution having normal or low potassium concentrations, [K(+)](o). We mapped action potentials (APs) on the cut-exposed transmural surface of the wedges in control, after CsCl, and CsCl with 0.15 mumol/l isoproterenol (CsCl+ISP). CsCl delayed late phase 3 repolarization and prolonged the duration of the AP, more so during low [K(+)](o) perfusion. Rapid pacing induced delayed afterdepolarizations (DADs) in all low [K(+)](o) and in 71% of normal [K(+)](o) preparations after CsCl treatment. Addition of ISP induced DADs in all preparations. DADs originated in mid-to-endocardium, and initiated VT after CsCl+ISP. Migration of DAD-VT foci resulted in multifocal VT. Alternating DADs at 2 foci resulted in bidirectional VT. There were more foci and longer durations of VT at low [K(+)](o) than at normal [K(+)](o). Delayed late phase 3 repolarization of APs and DADs generated U waves. Verapamil abolished all DADs and VT. CONCLUSIONS: CsCl blockade of I(K1) produced a ventricular wedge model of ATS. Suppressing I(K1) generated U waves by delaying late repolarization of APs and creating DADs, and promoted polymorphic VT by triggering DADs at multiple shifting sites.
Descriptors: andersen syndrome physiopathology, heart conduction system physiopathology, action potentials drug effects, adrenergic beta agonists pharmacology, andersen syndrome metabolism, calcium metabolism, calcium channel blockers pharmacology, cesium, chlorides, dogs, electrocardiography, endocardium metabolism, endocardium physiopathology, heart conduction system drug effects, isoproterenol pharmacology, models, animal, potassium metabolism, potassium channels drug effects, potassium channels metabolism, tissue culture techniques, verapamil pharmacology.

Morita, H., G. Suzuki, T. Mishima, P.A. Chaudhry, P.V. Anagnostopoulos, E.J. Tanhehco, V.G. Sharov, S. Goldstein, and H.N. Sabbah (2002). Effects of long-term monotherapy with metoprolol cr/xl on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Cardiovascular Drugs and Therapy 16(5): 443-449. ISSN: 0920-3206.
NAL Call Number: RM345
Abstract: We examined the effects of long-term monotherapy with the beta-blocker, metoprolol controlled release/extended release (CR/XL), on the progression of LV dysfunction as well as on global and cellular remodeling in dogs with heart failure (HF). Chronic HF was produced by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Dogs were randomized to 3 months oral monotherapy with metoprolol CR/XL (100 mg once daily, n=7) or no therapy at all (control, n=7). In control dogs, EF decreased from 38+-1% to 31+-2% (p=0.002), and LV end-systolic volume (ESV) and LV end-diastolic volume (EDV) increased (37+-2 vs 45+-2 ml, p=0.001; 59+-3 vs 65+-3 ml, p=0.001; respectively) during the 3 month follow-up period. In dogs treated with metoprolol CR/XL, EF increased after 3 months from 36+-1% to 43+-1% (p=0.001), and ESV decreased (42+-2 vs 38+-2 ml, p=0.003), whereas EDV remained unchanged. Compared to controls, treatment with metoprolol CR/XL showed 46% reduction in replacement fibrosis, 54% reduction in interstitial fibrosis and 20% reduction in myocyte cross-sectional area, a measure of myocyte hypertrophy. These findings indicate that metoprolol CR/XL improves LV function and attenuates progressive global and cellular LV remodeling in dogs with HF. The benefits are fully attributable to beta-blockade alone as no other adjunctive therapy was used.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, chronic heart failure, heart disease, left ventricular dysfunction, heart disease, drug therapy.

Morita, S.T., D.P. Zipes, H. Morita, and J. Wu (2007). Analysis of action potentials in the canine ventricular septum: no phenotypic expression of M cells. Cardiovascular Research 74(1): 96-103. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: OBJECTIVE: Transmural heterogeneity in the ventricular free wall, enhanced by the midmyocardial long action potential duration (APD) of M cells, plays an important role in the arrhythmogenesis of long QT syndrome. Although we observed dynamic expression of M cell phenotypes in the canine ventricular free wall, it is still unclear whether similar phenomena are present in the interventricular septum. This study evaluated transmural heterogeneity of APD in the septum. METHODS: We isolated and perfused 22 canine septal preparations through the septal branch of the anterior descending coronary artery, and optically mapped 256 channels of action potentials on their cut-exposed transseptal surfaces before and after treatment with sotalol (I(Kr) blocker), anemone toxin II (ATX-II, which slows the inactivation of I(Na)), or drug-free state in 6, 9, and 22 preparations, respectively. The preparations were paced from the left ventricular endocardium at cycle lengths of 500, 1000, 2000, and 4000 ms. RESULTS: We observed progressively lengthening of APD across the septum from the right ventricular to the left ventricular endocardium without a midmyocardial maximum under all conditions. All action potentials had minor phase-1 notches, resembling the endocardial action potential in the ventricular free wall. Increasing cycle lengths and concentrations of sotalol and ATX-II prolonged APD without midmyocardial preference and increased the transseptal dispersion of APDs. CONCLUSIONS: Canine interventricular septal action potentials are similar in shape to the endocardial action potentials in the ventricular free wall, with smooth transseptal transition in APD. We found no phenotypical expression of M cells in the canine interventricular septum.
Descriptors: action potentials physiology, heart conduction system physiology, heart septum physiology, action potentials drug effects, adrenergic beta antagonists pharmacology, cardiotonic agents pharmacology, cnidarian venoms pharmacology, dogs, endocardium physiology, heart septum drug effects, heart septum physiopathology, heart ventricles, long qt syndrome physiopathology, models, animal, perfusion, sotalol pharmacology.

Morris, T.A., J.J. Marsh, P.G. Chiles, R.G. Konopka, C.A. Pedersen, P.F. Schmidt, and M. Gerometta (2004). Single photon emission computed tomography of pulmonary emboli and venous thrombi using anti-d-dimer. American Journal of Respiratory and Critical Care Medicine 169(9): 987-993. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: Previous attempts to diagnose thromboemboli using radiolabeled antibodies and nuclear medicine imaging have been disappointing. We present the results of experiments with intravenous technetium-99m-labeled deimmunized antifibrin Fab' fragments to diagnose thromboemboli using single photon emission computed tomography (SPECT), a highly sensitive scintigraphic imaging technique. Pulmonary emboli (PEs) and lower extremity deep vein thrombi (DVTs) were formed in five dogs, then technetium-99m-labeled Fab' (dollar sign 400 mg, dollar sign 260 MBq) were injected via forelimb veins. Thoracic and lower extremity SPECT scans were performed at 2-hour intervals after antibody infusion to visualize the thromboemboli. Four hours after antibody infusion, all PEs and DVTs of mass 0.4g or greater were clearly visualized on SPECT scans as 'hot spots' within the lungs and legs, respectively. PEs (0.48 +/- 0.09 g) were intensely radiolabeled, yielding clot/blood radioactivity ratios of 22.8 +/- 5.6. DVTs (0.45 +/- 0.31 g) also had high clot/blood ratios (11.7 +/- 2.6). Infusion of these radiolabeled antibody fragments, combined with SPECT, produces clear images of PEs and DVTs within a clinically feasible time frame. The technique reliably identified even peripheral thromboemboli of relatively small size, which are difficult to diagnose with currently available imaging techniques, and may enable imaging of PEs, DVTs, or both in the same patient.
Descriptors: cardiovascular medicine, human medicine, medical sciences, pulmonary medicine, human medicine, radiology, medical sciences, deep vein thrombosis, vascular disease, pulmonary emboli, respiratory system disease, venous thrombi, vascular disease, venous thromboembolism, single photon emission computed tomography, spect, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques.

Morris, T.A., J.J. Marsh, R. Konopka, C.A. Pedersen, and P.G. Chiles (2004). Improved imaging of deep venous thrombi during anticoagulation using radiolabelled anti-d-dimer antibodies. Nuclear Medicine Communications 25(9): 917-922. ISSN: 0143-3636.
Abstract: Objectives Radiolabelled anti-fibrin antibodies have not yet enabled reliable and practical diagnosis of venous thromboembolism. However, previous unsuccessful clinical trials were performed with anti-fibrin P-chain antibodies that do not optimally bind to thrombi during anticoagulation. The current experiments were performed to determine if radiolabelled anti-D-dimer antibodies more reliably allowed nuclear medicine imaging of deep venous thrombi during anticoagulation than anti-beta-chain antibodies. Methods Dogs with pre-existing unilateral femoral vein thrombi were anticoagulated with heparin (300 units-kg bolus followed by 90 units.kg-1 .h-1 continuous infusion). They were then allocated to receive one of three 111In labelled antibodies: anti-D-dimer, anti-beta or a non-specific control antibody. Gamma scans of the legs were performed at regular intervals for 24 h. Scans were interpreted in a blinded fashion and the number of gamma counts from the femoral area on the thrombosed side was compared to the contralateral side. Clot/blood isotope density ratios were determined post-mortem. Results Leg thrombi were 100% detectable in the anti-D-dimer group, but only 60% detectable in the anti-beta group. Mean +/- SD relative counts in the thrombosed femoral area was 137 +/- 10% compared to the contralateral side in the anti-D-dimer group, but only 116 20% in the anti-P group. The clot/blood ratio was 24.5 +/- 2.8 in the anti-D-dimer group, but only 7.8 +/- 2.0 in the anti-beta group. Conclusions 111In labelled anti-D-dimer provides superior nuclear medicine images of thrombi during intensive anticoagulation compared to anti-beta. Clinical results with radiolabelled anti-D-dimer may be more promising than those previously observed with other anti-fibrin antibodies. Copyright 2004 Lippincott Williams & Wilkins.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, femoral vein thrombosis, vascular disease, diagnosis, drug therapy, gamma scan, imaging and microscopy techniques, laboratory techniques, indium 111 labelled anti d dimer antibody imaging, clinical techniques, diagnostic techniques.

Mousa, A., J. Bernheim, R. Dayal, S. Hollenbeck, M. Prince, P. Henderson, C. Kent, and P. Faries (2004). Implication of type ii endoleak on intra-aneurysmal pressure (canine model). FASEB Journal 18(4-5): Abst. 150.1. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, abdominal aortic aneurysm, vascular disease, aneurysm rupture, aneurysmal sac pressure, intra aneurysmal pressure, systemic pressure, type ii endoleak.

Nagueh, S.F., L. Rao, J. Soto, K.J. Middleton, and D.S. Khoury (2004). Haemodynamic insights into the effects of ischaemia and cycle length on tissue doppler-derived mitral annulus diastolic velocities. Clinical Science (London) 106(2): 147-154. ISSN: 0143-5221.
NAL Call Number: RB37.C43
Abstract: In the present study, we performed simultaneous epicardial echocardiography and left heart catheterization on ten adult dogs to investigate the effects of ischaemia and tachycardia on the mitral annulus early (Ea) and late (Aa) diastolic velocities and the haemodynamic mechanisms involved. Left atrial pressure and left ventricular (LV) volumes and pressures were measured with 5 French Millar catheters. In each dog, inferior vena cava occlusion was used to alter preload and circumflex coronary artery occlusion was applied to induce ischaemia at two different cycle lengths: 450 and 550 ms. At both cycle lengths, ischaemia resulted in a reduction in LV relaxation, LV global and ipsilateral systolic function, transmitral pressure gradient (TMG), Ea and Aa (P<0.05). The shorter cycle length was associated with a shorter tau (time constant of LV relaxation), reduced TMG and reduced septal and lateral Ea (P<0.05 for all variables). Both septal and lateral Aa were significantly increased (P<0.05). Ischaemia influences Ea through changes in LV relaxation, global and regional systolic function and TMG. An increase in heart rate reduces Ea, but increases Aa.
Descriptors: cardiovascular system, transport and circulation, myocardial ischemia, heart disease, vascular disease, diagnosis, tachycardia, diagnosis, epicardial echocardiography, diagnostic techniques, laboratory techniques, left heart catheterization, tissue doppler imaging, imaging and microscopy techniques.

Nagueh, S.F., L.A.R.A. Rao, J. Soto, K.J. Middleton, and D.S. Khoury (2002). Hemodynamic mechanisms that account for the variable effect of preload on tissue doppler early diastolic velocity. Circulation 106(19 Supplement): II.466. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, ischemia, vascular disease, myocardial dysfunction, heart disease, 5f millar catheter, laboratory equipment, echocardiography, laboratory techniques, left heart catheterization, experimental surgical techniques, tissue doppler imaging, imaging and microscopy techniques, contractility, early diastolic velocity, end systolic force, end systolic pressure, end systolic volume, hemodynamic mechanisms, late systolic load, transmitral pressure gradient.

Naito, M., X.P. Yang, and S. Chiba (2004). Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery. Clinical and Experimental Pharmacology and Physiology 31(3): 185-189. ISSN: 0305-1870.
Abstract: 1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2. Periarterial nerve electrical stimulation readily induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response. 3. Exposure of tissues to dipyridamole (0.1-1 mumol/L) dose-dependently inhibited both the first and second peaks of the vasoconstrictor response at a low frequency of stimulation (1 Hz), whereas at an intermediate frequency of stimulation (4 Hz), the first peak of the response was depressed without any significant effect being observed on the second peak of constriction. 4. At a higher dose (1 mumol/L) dipyridamole potentiated vasoconstrictor responses to noradrenaline (0.03-1 nmol). At any doses used, dipyridamole had no effect on the vasoconstrictor responses to ATP (0.03-1 mumol). 5. Tyramine (0.01-0.3 mumol) induced vasoconstriction in a dose-dependent manner. The dose-response curves for tyramine were shifted to the right following treatment with dipyridamole (0.1-1 mumol/L). 6. The present results indicate that dipyridamole may inhibit purinegic and adrenergic transmission presynaptically, whereas postsynaptically dipyridamole may potentiate the adrenergic vascular constriction by inhibition of transmitter uptake.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, cotransmission, neuronal vasoconstrictor response, transmitter release modification.

Nakamura, R. and K. Egashira (2001). Hmg-coa reductase inhibitor pravastatin ameriolates left ventricular dysfunction through inhibition of oxidative stress and inflammation in a canine model of tachycardia-induced heart failure. Circulation 104(17 Supplement): II.247. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, metabolism, pharmacology, heart failure, left ventricular dysfunction, heart disease, myocardial inflammation, heart disease, tachycardia, disease progression, left ventricular ejection fraction, left ventricular end diastolic pressure, oxidative stress, meeting abstract.

Nattel, S. (2007). The heart on a chip: the role of realistic mathematical models of cardiac electrical activity in understanding and treating cardiac arrhythmias. Heart Rhythm the Official Journal of the Heart Rhythm Society 4(6): 779-80. ISSN: 1547-5271.
Descriptors: arrhythmias, cardiac genetics, electrophysiology, heart ventricles physiopathology, long qt syndrome genetics, sodium channels genetics, arrhythmias, cardiac drug therapy, arrhythmias, cardiac physiopathology, dogs, long qt syndrome physiopathology, models, animal, models, theoretical.
Notes: Comment On: Heart Rhythm. 2007 Jun;4(6):768-78.

Nishida, K., A. Fujiki, K. Mizumaki, M. Sakabe, M. Sugao, T. Tsuneda, and H. Inoue (2004). Canine model of brugada syndrome using regional epicardial cooling of the right ventricular outflow tract. Journal of Cardiovascular Electrophysiology 15(8): 936-941. ISSN: 1045-3873.
Abstract: Canine Model of Brugada Syndrome. Introduction: Myocardial cooling can induce J point elevation (Osborn wave) as seen on ECG of the Brugada syndrome by activating transient outward current (Ito) and causing a spike-and-dome configuration of the monophasic action potential (MAP) in the ventricular epicardium in isolated canine ventricular wedge preparations. We determined the effect of regional epicardial cooling of the right ventricular outflow tract (RVOT) on surface ECG and ventricular vulnerability in the dog. Methods and Results: In 12 dogs, a cooling device (20-mm diameter) was attached to the RVOT epicardium, and surface ECG, epicardial MAP, and endocardial MAP were recorded. Regional cooling (29.7degreeC +/- 2.2degreeC) elevated the J point from 0.05 +/- 0.06 mV to 0.12 +/- 0.11 mV and induced T wave inversion (from 0.02 +/- 0.12 mV to -0.27 +/- 0.20 mV) in lead V1 in association with "spike-and-dome" configuration of the epicardial MAP. Cooling prolonged MAP duration in the RVOT epicardium from 172 +/- 27 ms to 213 +/- 30 ms (P < 0.01) but not in the RV endocardium and increased transmural dispersion of MAP duration from 9 +/- 8 ms to 44 +/- 21 ms (P < 0.01). Cooling also prolonged the QT interval in lead V1 from 191 +/- 19 ms to 212 +/- 23 ms (P < 0.05), but not in lead V5, and increased spatial dispersion of QT interval from 7 +/- 5 ms to 20 +/- 10 ms (P < 0.01). QT interval in lead V1 correlated positively with MAP duration in the RVOT epicardium (r = 0.75). T wave amplitude in lead V1 correlated inversely with transmural dispersion of MAP duration in the RVOT (r =-0.74). Vagal nerve stimulation accentuated the cooling-induced changes. During cooling, ventricular fibrillation was induced by a single extrastimulus in 2 of 4 dogs, and additional vagal nerve stimulation during isoproterenol administration induced spontaneous ventricular fibrillation in one dog. Conclusion: Localized epicardial cooling of the RVOT could be an in vivo experimental model of Brugada syndrome.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, nervous system, neural coordination, Brugada syndrome, bundle branch block, genetic disease, heart disease, diagnosis, ventricular fibrillation, chemically induced, electrocardiography, ecg, clinical techniques, diagnostic techniques, myocardial cooling, j point elevation, monophasic action potential, spike and dome configuration, ventricular vulnerability.

Nolan, E.R., M.B. Bailie, and N.B. Olivier (2008). Effect of autonomic blockade on ventricular repolarization shortening: response to behavioral stimulus in paced dogs. Autonomic Neuroscience Basic and Clinical 140(1-2): 66-71. ISSN: 1566-0702.
Abstract: Autonomic tone has been suggested to be a significant determinant of ventricular repolarization duration with both rate dependent and independent effects. Using the His bundle-paced dog, a model that eliminates the need for QT correction factors, we explored the rate-independent effects of sympathetic and parasympathetic blockade on ventricular repolarization shortening following an excitatory stimulus. Six male His bundle-paced beagle dogs were paced at 80 bpm and fitted with jackets, surface ECG electrodes, and radiotelemeters. Dogs were given propranolol, atropine methyl nitrate, or the appropriate control in a four-period crossover design. Doses were based on literature reviews and unpublished pharmacokinetic/pharmacodynamic modeling to provide efficacious beta- and parasympathetic blockade throughout the data collection period. Data collection began at 11 am and concluded at 11 am the following day, with event stimuli provided by investigators entering the room at 5 pm and at 7 am the following morning. One minute of ECG data were sampled every 15 min and these means were averaged to generate hourly means for the 24 hour data collection period. Treatment with atropine attenuated RT interval shortening when compared with the vehicle group at both the 5 pm and 7 am stimulus. In contrast, propranolol was not associated with significant effects on RT interval duration at either time point. These results suggest that parasympathetic withdrawal is the primary factor responsible during both awake hours (5 pm) and in the transition from deep sleep to the awake state (7 am) in the facilitation of RT interval shortening following an excitatory stimulus. The attenuation of RT interval shortening following atropine treatment may be a direct effect, or an indirect effect requiring an excited state to become evident. The use of a model that eliminates the need to apply correction factors to repolarization indices helps to clarify the role of the autonomic nervous system on ventricular repolarization.
Descriptors: autonomic nervous system physiology, heart innervation, heart physiology, heart rate physiology, heart ventricles innervation, ventricular function, adrenergic beta antagonists pharmacology, atropine pharmacology, autonomic nervous system drug effects, biological clocks drug effects, biological clocks physiology, bundle of his drug effects, bundle of his physiology, circadian rhythm physiology, dogs, electric stimulation, electrocardiography drug effects, heart rate drug effects, membrane potentials drug effects, membrane potentials physiology, models, animal, muscarinic antagonists pharmacology, pacemaker, artificial, parasympathetic nervous system drug effects, parasympathetic nervous system physiology, propranolol pharmacology, sympathetic nervous system drug effects, sympathetic nervous system physiology, time factors.

Nozari, A., P. Safar, S.W. Stezoski, X. Wu, J. Henchir, A. Radovsky, K. Hanson, E. Klein, P.M. Kochanek, and S.A. Tisherman (2004). Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation increases conscious survival in dogs. Critical Care Medicine. 32(10): 2110-6. ISSN: 0090-3493.
Abstract: OBJECTIVE: Therapeutic hypothermia during cardiac arrest and after restoration of spontaneous circulation enables intact survival after prolonged cardiopulmonary cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We hypothesized that mild to moderate hypothermia during CPCR would increase the rate of neurologically intact survival after prolonged cardiac arrest in dogs. DESIGN: Randomized, controlled study using a clinically relevant cardiac arrest outcome model in dogs. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (19-29 kg; three were excluded from outcome evaluation). INTERVENTIONS: Dogs were subjected to cardiac arrest no-flow of 3 mins, followed by 7 mins of basic life support and 10 mins of simulated unsuccessful advanced life support attempts. Another 20 mins of advanced life support continued with four treatments: In control group 1 (n = 7), CPCR was with normothermia; in group 2 (n = 6, 1 of 7 excluded), with moderate hypothermia via venovenous extracorporeal shunt cooling to tympanic temperature 27 degrees C; in group 3 (n = 6, 2 of 8 excluded), the same as group 2 but with mild hypothermia, that is, tympanic temperature 34 degrees C; and in group 4 (n = 5), with normothermic venovenous shunt. After 40 mins of ventricular fibrillation, reperfusion was with cardiopulmonary bypass for 4 hrs, including defibrillation to achieve spontaneous circulation. All dogs were maintained at mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs. Intensive care was to 96 hrs. MEASUREMENTS AND MAIN RESULTS: Overall performance categories and neurologic deficit scores were assessed from 24 to 96 hrs. Regional and total brain histologic damage scores and extracerebral organ damage were assessed at 96 hrs.In normothermic groups 1 and 4, all 12 dogs achieved spontaneous circulation but remained comatose and (except one) died within 58 hrs with multiple organ failure. In hypothermia groups 2 and 3, all 12 dogs survived to 96 hrs without gross extracerebral organ damage (p < .0001). In group 2, all but one dog achieved overall performance category 1 (normal); four of six dogs had no neurologic deficit and normal brain histology. In group 3, all dogs achieved good functional outcome with normal or near-normal brain histology. Myocardial damage scores were worse in the normothermic groups compared with both hypothermic groups (p < .01). CONCLUSION: Mild or moderate hypothermia during prolonged CPCR in dogs preserves viability of extracerebral organs and improves outcome.
Descriptors: animal model, hypothermia, cardiac arrest, cardiopulmonary cerebral resuscitation (CPCR), brain histology, improved outcome.

Nozari, A., P. Safar, S. Tisherman, X. Wu, and S.W. Stezoski (2002). Hypothermia induced during cardiopulmonary resuscitation increases intact survival after prolonged normovolemic cardiac arrest in dogs. 2002 Annual Meeting of the American Society of Anesthesiologists, Orlando, FL, USA; October 12-16, 2002,
Online: http://www.asa-abstracts.com
Abstract: Studies by us and others have documented improved cerebral outcome with mild hypothermia (34degreeC) induced after cardiac arrest (CA) and restoration of spontaneous circulation (ROSC). We hypothesized that in a simulated unresuscitable CA dog model, intact survival can be achieved if hypothermia is induced during prolonged cardiopulmonary resuscitation (CPR) steps A-B-C. Twelve dogs (20-25 kg) were subjected to 3 min of CA no-flow with ventricular fibrillation (VF), followed by 7 min CPR Basic Life Support and 30 min of unsuccessful CPR Advanced Life Support (ALS) with DC countershocks, FiO2 1.0 and epinephrine boluses. Dogs were randomly allocated into two treatment groups: a control group with normothermic VF (n=6, tympanic temperature (Tty) 37.5degreeC throughout) and a hypothermia group (n=6) which received at VF 20 min a venous flush of 20 ml/kg normal saline at 2degreeC followed by veno-venous extra-corporeal blood cooling (cetheters in superior and inferior vena cava) until cardiopulmonary bypass (CPB) was initiated at VF 40 min. ROSC and assisted circulation were with CPB to 4 h and then mild hypothermia (Tty 34degreeC) to 12 h, controlled ventilation to 48 h, and intensive care to 96 h. Outcome was evaluated as overall performance categories (OPC 1 = normal, 2 = moderate disability, 3 = severe disability, 4 = coma, 5 = death); neurologic deficit scores (NDS 0-10% = normal, 100% = brain death); and 96 h perfusion fixation, necropsy, and determination of total and regional brain histologic damage scores (HDS). Lowest Tty in the hypothermia group was 27degreeC (range 26-28degreeC). ROSC was achieved in all 12 dogs. In the control group, 1 dog survived to 96 h but remained comatose (OPC 4); and 5 dogs died during the intensive care period, the majority within 24 h, because of malignant arrhythmias and respiratory failure or vasopressor resistant shock; "best" NDS was 92% (range 92 - 98%). In the hypothermia group, 5 of the 6 dogs survived to 96 h with good neurologic outcome - OPC 1 (P=0.025) and NDS 0% (0-7%). HDS results are pending. In the control group there were renal failure and intestinal mucosal necrosis, severe subendocardial and epicardial hemorrhagic infarctions, and pulmonary infarctions. In the hypothermia group morphologic changes were absent or minimal (one with bilateral hemorrhagic pulmonary consolidations, 2 with mild subendocardial hemorrhage). In conclusion, cooling during CPR attempts in prolonged normovolemic and presently unresuscitable cardiac arrest, as a bridge to prolonged CPB, results in survival with full neurologic recovery. A portable device for veno-venous cooling should be developed.
Descriptors: cardiovascular system, transport and circulation, cardiac arrest, heart disease, epicardial hemorrhagic infarction, pulmonary infarction, respiratory system disease, cardiopulmonary resuscitation, clinical techniques, therapeutic and prophylactic techniques, hypothermia, laboratory techniques.

Ojalvo, A.-G., A. Seralena, R. Vazquez, J.-F. Montequin, N.-S. Vispo, R. Silva, A. Aldama, Y. Puchades, L.-T. Sorell, P. Lopez-Saura, M.-A. Alfonso, R. Simon, A. Ali, A. Seuc, and L. Herrera (2003). Therapeutic angiogenesis following intramuscular gene transfer of vascular endothelial growth factor 121 in a dog model of hindlimb ischemia. Electronic Journal of Biotechnology 6(3 Cited December 31, 2003) ISSN: 0717-3458.
Online: http://www.ejbiotechnology.info
Abstract: Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, has been shown to promote therapeutic angiogenesis in animal models of critical limb ischemia. Ischemic skeletal muscle is advantageous for taking up and expressing foreign genes transferred as naked plasmid DNA. Accordingly, we investigated the hypothesis that intramuscular administration of naked plasmid DNA encoding the 121-amino acid isoform of VEGF could augment collateral development and tissue perfusion in a dog hindlimb ischemia model. Unilateral hindlimb ischemia was surgically induced in Beagle dogs. Ten days later, animals received intramuscular injections of pVEGF121 plasmid directly in the ischemic muscles. Angiogenic effects were evaluated by angiography, calf blood pressure ratio and vasomotor reserve analyses. Thirty days after gene transfer, angiographically recognizable collateral vessels were increased in pVEGF121-treated animals compared with controls. Improvement in perfusion to the ischemic limb was documented by a significantly higher calf blood pressure ratio for pVEGF121 (0.79 +- 0.05) versus controls (0.56 +- 0.14, P<0.01). Vasomotor reserve assay suggested amelioration in blood availability at the microcirculation level in pVEGF121-treated animals. Hematological variables showed no significant modification due to the treatment. Our results suggest that intramuscular gene transfer of VEGF121 may promote therapeutic angiogenesis in critical limb vascular insufficiency.
Descriptors: cardiovascular system, transport and circulation, molecular genetics, biochemistry and molecular biophysics, muscular system, movement and support, hindlimb ischemia, vascular disease, therapy , angiography , imaging and microscopy techniques, laboratory techniques, intramuscular gene transfer, genetic techniques, vasomotor reserve assay, bioassay techniques, blood pressure, therapeutic angiogenesis.

Okada, D.R., G. Johnson, Z. Liu, S.D. Hocherman, B.A. Khaw, and R.D. Okada (2004). Early detection of infarct in reperfused canine myocardium using 99mtc-glucarate. Journal of Nuclear Medicine 45(4): 655-664. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Abstract: 99mTc-Glucarate is an infarct-avid imaging agent with the potential for very early detection of myocardial infarction. The purposes of this study using a canine model were to determine (a) the time course of 99mTc-glucarate uptake and clearance from necrotic and normal myocardium; (b) the 99mTc-glucarate necrotic-to-normal activity ratio over time; (c) the time course of detectable scan positivity after intravenous administration of the tracer; and (d) the relationship of infarct size determined by triphenyltetrazolium chloride (TTC) staining versus 99mTc-glucarate imaging ex vivo. Methods: A 90-min left circumflex coronary artery (LCx) occlusion was followed by 270 min of reperfusion at 100% baseline flow in 6 open-chest, anesthetized dogs. 99mTc-Glucarate (555 MBq (15 mCi)) was injected 30 min after reperfusion and was followed by 240 min of gamma-camera serial imaging. Microspheres were injected during baseline, occlusion, tracer injection, and before the dogs were euthanized. Creatine kinase assays were performed to assess developing injury. Ex vivo gamma-camera imaging was performed. Blood flow and tracer activity were determined by well counting. TTC stain was used to mark infarct areas, which were sized using computerized digital planimetry. Results: Hemodynamics demonstrated no significant change from baseline at any time for any parameter except LCx flow, which was significantly depressed during occlusion. The mean infarct size +/- SEM was 10.7% +/- 2% of total left ventricle. Blood 99mTc-glucarate clearance was triexponential and rapid. Qualitative image analysis revealed a well defined hot spot after 30 min, which remained well defined through 240 min after injection (150 and 360 min after occlusion, respectively). Images were quantitatively abnormal with hot spot-to-normal zone activity ratios of gtoreq2:1 within 10 min of tracer administration (130 min after occlusion), reaching 8:1 at 240 min after tracer administration (360 min after occlusion). There was a linear correlation between infarct size determined by 99mTc-glucarate and TTC staining (r = 0.96; slope = 0.87). Conclusion: 99mTc-Glucarate marks acute myocardial infarct very early after occlusion and appears to accurately assess infarct size when compared with TTC staining.
Descriptors: cardiovascular system, transport and circulation, radiology, medical sciences, veterinary medicine, medical sciences, myocardial infarction, heart disease, vascular disease, ex vivo gamma camera imaging, imaging and microscopy techniques, laboratory techniques.

Olivier, N.B., G.E. Eyster, R. Sanders, J. Cheng, G. Bohart, M. Girand, and M. Bailie (2003). Atrioventricular nodal ablation and his-bundle pacing: an acute canine model for proarrhythmic risk assessment. Journal of Cardiovascular Electrophysiology 14(12): 1356-1360. ISSN: 1045-3873.
Abstract: Introduction: QT interval prolongation following drug exposure is considered a marker for increased risk of drug-induced arrhythmias. QT interval measurements are common components of the safety pharmacology assessment of new therapeutic compounds but are potentially confounded by concurrent changes in heart rate that also alter QT intervals. We describe an anesthetized canine model of AV dissociation with His-bundle pacing that overcomes the confounding effects of a change in heart rate. Methods and Results: Transvenous radiofrequency ablation of the AV node was performed in isoflurane-anesthetized dogs and followed by open chest implantation of bipolar pacing electrodes in the vicinity of the His bundle. Pace rates were adjusted from 50 to 190 in steps of 20 beats/min, holding each step for 30 seconds. At each paced rate, QT intervals were measured manually to the nearest 1 ms to construct paced QT interval-heart rate (QT-HR) relationships. Paired QT-HR relationships using identical ascending ramps of pace rates were compared to paired QT-HR relationships with an ascending and descending pace ramp to evaluate short-term reproducibility and hysteresis effects. For proof of concept, an additional QT-HR relationship was constructed in three dogs after intravenous administration of a compound known to alter QT intervals: one dog received terfenadine (0.48 mg/kg bolus followed by 0.017 mg/kg/min infusion), one dog received quinidine (20 mg/kg), and the third dog received sotalol (1 and 3 mg/kg). Substantial interdog variation was found for QT-HR, although short-term reproducibility was high within one dog (average absolute difference for paired ascending ramps <5 ms). QT intervals measured during descending paced ramps were generally lower than the value for the corresponding paced rate on an ascending ramp. This hysteretic effect was small, averaging <7 ms over the entire ramp. All test compounds prolonged QT intervals and shifted the QT-HR relationship upward. Maximal QT prolongation was 30 ms for terfenadine, 50 ms for quinidine, and 59 ms for sotalol. Conclusion: AV nodal ablation and His-bundle pacing provide a sensitive animal model to identify acute effects of test compounds on indices of myocardial repolarization such as the QT interval. The model is devoid of confounding effects of changing heart rates while enabling identification of effects of drugs over a wide range of controlled rates.
Descriptors: cardiovascular system, transport and circulation, pharmacology, his bundle pacing, diagnostic techniques, atrioventricular nodal ablation, clinical techniques, therapeutic and prophylactic techniques, qt interval, drug effects, heart rate changes, confounding effects, proarrhythmic risk assessment.

Ollerstam, A., S.A. Visser, G. Duker, T. Forsberg, A.H. Persson, L.B. Nilsson, J.A. Bjorkman, J. Gabrielsson, and A. Al Saffar (2007). Comparison of the QT interval response during sinus and paced rhythm in conscious and anesthetized beagle dogs. Journal of Pharmacological and Toxicological Methods 56(2): 131-44. ISSN: 1056-8719.
NAL Call Number: QP901.J6
Abstract: INTRODUCTION: The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different pharmacological and pharmacokinetic profiles. METHOD: Dofetilide and moxifloxacin were tested in all models, whereas cisapride and terfenadine were tested in the conscious telemetered and paced models. All substances were given as two consecutive 1.5-h intravenous infusions (infusions 1 and 2). The individual concentration-time courses of dofetilide, moxifloxacin, and cisapride were linked to the drug-induced effects on the QT interval and described with a pharmacokinetic-pharmacodynamic model to obtain an estimate of the unbound plasma concentrations at steady state that give a 10- and 20-ms drug-induced QT interval prolongation (CE10ms and CE20ms). RESULTS: In the conscious telemetered, conscious paced, and anesthetized dog models, the mean CE10ms values were 1.4, 4.0, and 2.5 nM for dofetilide and 1300, 1800, and 12,200 nM for moxifloxacin. For cisapride, the CE10ms values were 8.0 and 4.4 nM in the conscious telemetered and conscious paced dog models. The drug-induced QT interval prolongation during the last 30 min of infusions 1 and 2 was comparable in the conscious models, but smaller in the anesthetized dog model. Terfenadine displayed a marked delay in onset of response, which could only be detected by the extended ECG recording. DISCUSSION: All dog models investigated detected QT interval prolongation after administration of the investigated test substances with similar sensitivity, except for a lower sensitivity in the anesthetized dogs following moxifloxacin administration. The conscious telemetered dog model was favorable, mainly due to the extended continuous ECG recording, which facilitated detection and quantification of delayed temporal differences between systemic exposure and drug-induced QT interval prolongation.
Descriptors: cardiac pacing, artificial, long qt syndrome physiopathology, sinoatrial node physiopathology, telemetry methods, anesthesia, aza compounds administration and dosage, aza compounds pharmacokinetics, aza compounds toxicity, cisapride administration and dosage, cisapride pharmacokinetics, cisapride toxicity, consciousness, dogs, dose response relationship, drug, drug evaluation, preclinical methods, electrocardiography methods, ether a go go potassium channels physiology, half life, heart rate drug effects, infusions, intravenous, long qt syndrome chemically induced, models, animal, phenethylamines administration and dosage, phenethylamines pharmacokinetics, phenethylamines toxicity, quinolines administration and dosage, quinolines pharmacokinetics, quinolines toxicity, sinoatrial node drug effects, sulfonamides administration and dosage, sulfonamides pharmacokinetics, sulfonamides toxicity, terfenadine administration and dosage, terfenadine pharmacokinetics, terfenadine toxicity, time factors.

Opthof, T., R. Coronel, F.J. Wilms Schopman, A.N. Plotnikov, I.N. Shlapakova, P.J. Danilo, M.R. Rosen, and M.J. Janse (2007). Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion. Heart Rhythm the Official Journal of the Heart Rhythm Society 4(3): 341-8. ISSN: 1547-5271.
Abstract: BACKGROUND: The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. OBJECTIVES: The purpose of this study was to test the relationship of T(p-e) to transmural dispersion of repolarization by correlating local repolarization times at endocardial, midmural, and epicardial sites in the left and right ventricles with the T wave of the ECG. METHODS: Local activation times, activation-recovery intervals, and repolarization times were measured at 98 epicardial sites and up to 120 midmural and endocardial sites in eight open-chest dogs. In four of the dogs, long-term cardiac memory was induced by 3 weeks of ventricular pacing at 130 bpm because previous data suggest that, in this setting, delayed epicardial repolarization increases transmural dispersion. The other four dogs were sham operated. RESULTS: In sham dogs, T(p-e) was 41 +/- 2.2 ms (X +/- SEM), whereas the transmural dispersion of repolarization time was 2.7 +/- 4.2 ms (not significant between endocardium and epicardium). Cardiac memory was associated with evolution of a transmural gradient of 14.5 +/- 1.9 ms (P <.02), with epicardium repolarizing later than endocardium. The corresponding T(p-e) was 43 +/- 2.3 ms (not different from sham). In combined sham and memory dogs, T(p-e) intervals did not correlate with transmural dispersion of repolarization times. In contrast, dispersion of repolarization of the whole heart (measured as the difference between the earliest and the latest moment of repolarization from all left and right ventricular, endocardial, intramural, and epicardial recording sites) did correlate with T(p-e) (P <.0005, r = 0.98), although the latter underestimated total repolarization time by approximately 35%. The explanation for this finding is that parts of the heart fully repolarize before the moment of T(peak). CONCLUSION: T(p-e) does not correlate with transmural dispersion of repolarization but is an index of total dispersion of repolarization.
Descriptors: electrocardiography, heart conduction system physiology, action potentials, analysis of variance, cardiac pacing, artificial, dogs, electrodes, implanted, electrophysiologic techniques, cardiac, endocardium physiology, image processing, computer assisted, linear models, models, animal, models, cardiovascular, pericardium physiology, research design, ventricular function.
Notes: Comment In: Heart Rhythm. 2007 Aug;4(8):1114-6; author reply 1116-9.

Oyama, M.A., B.J. Bulmer, and D. Sisson (2003). Estimation of left atrial pressure using doppler tissue imaging in a canine model of valvular insufficiency. Journal of the American College of Cardiology 41(6 Supplement A): 440A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, acute mitral valve regurgitation, heart disease, valvular insufficiency, heart disease, doppler tissue imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, swan ganz catheter, surgical instrument, left atrial pressure estimation, clinical techniques, early mitral inflow velocity, early mitral valve annular velocity.

Pagala, M., M. Vaynblat, S. Karaka, Y. Zhukovskiy, P. Shah, R. Fazylov, and J.N. Cunningham (2004). Influence of premature ventricular complex on left ventricular pressure in dog heart. FASEB Journal 18(4-5): Abst. 202.12. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, ekg, electrocardiogram, laboratory techniques, qrs complex, excitation contraction coupling, left ventricular pressure, premature ventricular complex.

Pagala, M.K., P. Shah, M. Raval, S. Abrol, and J.N.J. Cunningham (2003). Changes in superoxide dismutase activity in cerebrospinal fluid and serum during spinal cord ischemia and reperfusion in a dog model. FASEB Journal 17(4-5): Abstract No. 567.9. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: superoxide dismutase (SOD), antioxidant enzyme, free radicals, cardiovascular system, transport and circulation, enzymology, biochemistry and molecular biophysics, nervous system, neural coordination, ischemic spinal cord injury, injury, nervous system disease, vascular disease, pathology, spinal cord ischemia, reperfusion, injury, nervous system disease, vascular disease, pathology, aortic cross clamping, experimental surgical techniques, laboratory techniques.

Pap Szekeres, J., G. Cserni, I. Furka, M. Svebis, T. Cserni, E. Brath, N. Nemeth, and I. Miko (2003). Transplantation and microsurgical anastomosis of free omental grafts: experimental animal model of a new operative technique in dogs. Microsurgery 23(5): 414-418. ISSN: 0738-1085.
Abstract: Our objective was the elaboration of a new animal model for the free transplantation of an omental flap and the examination of its viability in dogs. The cooled omental flap from the abdomen was freely transplanted to the lateral cervical region, and its blood supply was established with microsurgical anastomoses. The technique was developed in 5 dogs, and short-term survival examinations were later carried out in 3 cases by means of this method. Postoperative viability was assessed by angiography, methylene blue testing, and histology. Of the 3 transplanted grafts, 2 still survived 1 week after the operation. For technical reasons, 1 flap thrombotized. For determination of the viability of the transplanted graft, histology proved best. Vital reactions, including granulation tissue and angiogenesis, were present on the histological slides. The short-term survival of an omental flap can be ensured with microsurgical transplantation in dogs.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, microsurgical anastomosis, experimental surgical techniques, laboratory techniques, omental flap transplantation, experimental surgical techniques, histology.

Patel, C. and C. Antzelevitch (2008). Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm the Official Journal of the Heart Rhythm Society 5(4): 585-90.
Abstract: BACKGROUND: Short QT syndrome (SQTS) is a primary electrical disease of the heart associated with a high risk of sudden cardiac death. A gain-of-function in I(Kr), due to a mutation in KCNH2, underlies SQT1. OBJECTIVE: This study sought to examine the cellular basis for arrhythmogenesis in an experimental model of SQT1 created using PD-118057, a novel I(Kr) agonist. METHODS: Transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial regions of arterially perfused canine left ventricular (LV) wedge preparations, together with a pseudo-electrocardiogram. RESULTS: PD-118057 (10 micromol/l) abbreviated the QT interval from 267 +/- 4 to 232 +/- 4 ms and increased transmural dispersion of repolarization (TDR) from 33.7 +/- 2.0 to 49.1 +/- 3.1 ms (P <.001). T-wave amplitude increased from 18.0% +/- 1.4% to 23.1% +/- 1.7% of R-wave amplitude (P =.027). Reversing the direction of activation of the LV wall (epicardial pacing) resulted in an increase in QT interval from 269 +/- 5 to 282 +/- 5 ms and an increase in TDR from 34.1 +/- 2.0 to 57.6 +/- 3.3 ms (P <.001) under baseline conditions. PD-118057 abbreviated the QT interval from 282 +/- 5 to 258 +/- 5 ms and produced a proportional decrease in effective refractory period (ERP). TDR increased from 57.6 +/- 3.3 to 77.6 +/- 4.3 ms (P <.001). Polymorphic ventricular tachycardia (pVT) was induced in 10 of 20 preparations with a single S(2) applied to epicardium. Quinidine (10 micromol/l) increased the ERP and QT interval, did not significantly alter TDR, and prevented induction of pVT in 5 of 5 preparations. CONCLUSION: Our results suggest that a combination of ERP abbreviation and TDR amplification underlie the development of pVT in SQT1 and that quinidine prevents pVT principally by prolonging ERP.
Descriptors: anthranilic acids pharmacology, arrhythmias, cardiac physiopathology, death, sudden, cardiac etiology, death, sudden, cardiac pathology, action potentials genetics, anti arrhythmia agents pharmacology, arrhythmias, cardiac genetics, dogs, electrophysiology, endocardium physiopathology, ether a go go potassium channels genetics, heart ventricles physiopathology, membrane potentials, models, animal, models, theoretical, pericardium physiopathology, potassium channels drug effects, quinidine pharmacology, risk factors.
Notes: Comment In: Heart Rhythm. 2008 Apr;5(4):591-2.

Pavcnik, D., R.T. Andrews, Q. Yin, B.T. Uchida, H.A. Timmermans, C. Corless, N. Toyota, M. Nakata, J. Kaufman, F.S. Keller, and J. Rosch (2003). A canine model for studying endoleak after endovascular aneurysm repair. Journal of Vascular and Interventional Radiology 14(10): 1303-10. ISSN: 1051-0443.
Abstract: PURPOSE: The aim of this study was to create an animal model of endoleak after stent-graft placement for abdominal aortic aneurysm (AAA) in which a large aneurysmal sac would be preserved for the testing of techniques for its percutaneous occlusion. MATERIALS AND METHODS: Infrarenal AAAs were created in nine dogs by anastomosis of an isolated segment of the inferior vena cava to the right side of the abdominal aorta in combination with a large anterior patch from the external jugular vein. One hour later, animals underwent percutaneous implantation of polytetrafluoroethylene-covered Z stent endografts with three 3-mm-diameter holes through the fabric. Aortograms were obtained before and after surgery, after endograft placement, and at the time of animal sacrifice at 1 week or 1, 2, 3, or 6 months. Pressures within the aorta and the aneurysm sac were recorded before animal sacrifice. Gross and histologic evaluations of the specimens were then carried out. RESULTS: Immediately after endograft placement, all nine animals had artificial type III endoleaks with angiographic filling of lumbar arteries and veins. One animal died of surgical complications within 2 days of surgery and is not included in our data analysis. One aneurysm ruptured at 1 week. At completion of the study, six endografts were patent and two were occluded. The aneurysm sac had enlarged by approximately 50% in seven animals. At follow-up, type I endoleak was present in three animals, type II endoleak was present in three, and the artificial type III endoleak was present in all six animals with patent endografts. The pressure differential between aorta and aneurysm sac was 36 mm Hg, with a mean aortic pressure of 87 mm Hg +/- 13.3 and a mean aneurysmal sac pressure of 51 mm Hg +/- 28.1. The aneurysmal sac exhibited early thrombus formation at 1 week, which progressed to complete thrombosis in 1-6 months. CONCLUSIONS: The model is technically feasible but would be useful in testing occlusive techniques for residual aneurysm sacs only in the acute phase after endograft placement. It would be not reliable for chronic evaluation because of rapidly progressive thrombosis in most aneurysm sacs and occasional complete thrombosis of the AAA and endograft.
Descriptors: animal model, endoleak, abdominal aortic aneurysm, polytetrafluoroethylene-covered Z stent endografts .

Phillips, S.J., A.B. Kantrowitz, G. Zorzi, L. Zoireff, D. Jaron, P. Freed, and P. Cascade (2007). Experimental intraaortic balloon pumping prior to acute myocardial infarction. 1973. Journal of Extra Corporeal Technology 39(2): 125-8; Discussion 117-8. ISSN: 0022-1058.
Descriptors: heart assist devices history, intra aortic balloon pumping history, myocardial infarction, acute disease, dogs, history, 20th century, models, animal, myocardium, survival analysis.

Pirat, B., D.S. Khoury, C.J. Hartley, L. Tiller, L. Rao, D.G. Schulz, S.F. Nagueh, and W.A. Zoghbi (2008). A novel feature-tracking echocardiographic method for the quantitation of regional myocardial function: validation in an animal model of ischemia-reperfusion. Journal of the American College of Cardiology 51(6): 651-9.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: The aim of this study was to validate a novel, angle-independent, feature-tracking method for the echocardiographic quantitation of regional function. BACKGROUND: A new echocardiographic method, Velocity Vector Imaging (VVI) (syngo Velocity Vector Imaging technology, Siemens Medical Solutions, Ultrasound Division, Mountain View, California), has been introduced, based on feature tracking-incorporating speckle and endocardial border tracking, that allows the quantitation of endocardial strain, strain rate (SR), and velocity. METHODS: Seven dogs were studied during baseline, and various interventions causing alterations in regional function: dobutamine, 5-min coronary occlusion with reperfusion up to 1 h, followed by dobutamine and esmolol infusions. Echocardiographic images were acquired from short- and long-axis views of the left ventricle. Segment-length sonomicrometry crystals were used as the reference method. RESULTS: Changes in systolic strain in ischemic segments were tracked well with VVI during the different states of regional function. There was a good correlation between circumferential and longitudinal systolic strain by VVI and sonomicrometry (r = 0.88 and r = 0.83, respectively, p < 0.001). Strain measurements in the nonischemic basal segments also demonstrated a significant correlation between the 2 methods (r = 0.65, p < 0.001). Similarly, a significant relation was observed for circumferential and longitudinal SR between the 2 methods (r = 0.94, p < 0.001 and r = 0.90, p < 0.001, respectively). The endocardial velocity relation to changes in strain by sonomicrometry was weaker owing to significant cardiac translation. CONCLUSIONS: Velocity Vector Imaging, a new feature-tracking method, can accurately assess regional myocardial function at the endocardial level and is a promising clinical tool for the simultaneous quantification of regional and global myocardial function.
Descriptors: coronary vessels physiopathology, myocardial ischemia physiopathology, myocardial reperfusion, myocardium, blood flow velocity, coronary vessels ultrasonography, dobutamine, dogs, endocardium, models, animal, myocardial ischemia ultrasonography, propanolamines, systole.

Plotnikov, A.N., E.A. Sosunov, J. Qu, I.N. Shlapakova, E.P. Anyukhovsky, L. Liu, M.J. Janse, P.R. Brink, I.S. Cohen, R.B. Robinson, P.J. Danilo, and M.R. Rosen (2004). Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates. Circulation 109(4): 506-512. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background: We hypothesized that administration of the HCN2 gene to the left bundle-branch (LBB) system of intact dogs would provide pacemaker function in the physiological range of heart rates. Methods and Results: An adenoviral construct incorporating HCN2 and green fluorescent protein (GFP) as a marker was injected via catheter under fluoroscopic control into the posterior division of the LBB. Controls were injected with an adenoviral construct of GFP alone or saline. Animals were monitored electrocardiographically for up to 7 days after surgery, at which time they were anesthetized and subjected to vagal stimulation to permit emergence of escape pacemakers. Hearts were then removed and injection sites visually identified and removed for microelectrode study of action potentials, patch clamp studies of pacemaker current, and/or immunohistochemical studies of HCN2. For 48 hours postoperatively, 7 of 7 animals subjected to 24-hour ECG monitoring showed multiple ventricular premature depolarizations and/or ventricular tachycardia attributable to injection-induced injury. Thereafter, sinus rhythm prevailed. During vagal stimulation, HCN2-injected dogs showed rhythms originating from the left ventricle, the rate of which was significantly more rapid than in the controls. Excised posterior divisions of the LBB from HCN2-injected animals manifested automatic rates significantly greater than the controls. Isolated tissues showed immunohistochemical and biophysical evidence of overexpressed HCN2. Conclusions: A gene-therapy approach for induction of biological pacemaker activity within the LBB system provides ventricular escape rhythms that have physiologically acceptable rates. Long-term stability and feasibility of the approach remain to be tested.
Descriptors: cardiovascular system, transport and circulation, molecular genetics, biochemistry and molecular biophysics, veterinary medicine, medical sciences, ventricular tachycardia, heart disease, electrocardiography, clinical techniques, diagnostic techniques, gene therapy, clinical techniques, genetic techniques, laboratory techniques, therapeutic and prophylactic techniques, immunohistochemistry, immunologic techniques, laboratory techniques, patch clamp, histology and cytology techniques, action potential, biological pacemaker, heart rate, sinus rhythm, ventricular escape rhythms.

Potse, M., P.F.H.M. Van Dessel, A.C. Linnenbank, C.A. Grimbergen, N.M. Van Hemel, and J.M.T. De Bakker (2004). Properties of unipolar electrograms recorded with a multielectrode basket catheter. Journal of Electrocardiology 37(1): 1-10. ISSN: 0022-0736.
Abstract: In the past few years, clinical trials with multielectrode "basket" catheters have provided unique recordings from the endocardium of intact in-situ human hearts. Analysis of these recordings is difficult because unipolar electrograms obtained from a basket catheter in the blood-filled cavity differ from those obtained by other mapping techniques such as endocardial balloons used during antiarrhythmic surgery. We investigated these differences using basket catheter recordings obtained in isolated porcine and canine hearts that could be filled with perfusion fluid and evacuated at will. The results indicated that the differences between basket and balloon recordings are largely attributable to the presence and absence of blood. Activation maps obtained in the presence and absence of blood were usually similar and only differed in a minority of cases at sites in which electrograms revealed multiple deflections. In conclusion, unipolar mapping using a basket catheter can be used with confidence for the creation of activation maps if appropriate care is taken in the interpretation of fractionated electrograms.
Descriptors: cardiovascular system, transport and circulation, endocardial mapping, laboratory techniques, multielectrode basket catheter, laboratory equipment, unipolar electrogram recording, activation map.

Prasad, K., J.B. Gupta, J. Kalra, P. Lee, S.V. Mantha, and B. Bharadwaj (1996). Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model. Journal of Molecular and Cellular Cardiology 28(2): 375-385. ISSN: 0022-2828.
Abstract: We investigated the effects of chronic volume overload in the absence or presence of vitamin E supplements on the cardiac function and contractility, cardiac malondialdehyde (MDA) - a lipid peroxidation product - cardiac antioxidant enzyme activity and antioxidant reserve in canine model. The dogs were divided into three groups of seven dogs each: group I, control; group II, mitral regurgitation (MR) of 4 months duration; and group III, MR of 4 months duration receiving vitamin E (40 U/kg/daily) orally. MR was created by detaching two or more chordae tendinae to raise left atrial pressure to 2.5 to three times normal. MR produced a decrease in the index of myocardial contractility with little change in myocardial function. Decrease in myocardial (left and right ventricles) contractility was associated with an increase in cardiac MDA, and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload-induced decrease in myocardial contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated group. The results indicate that chronic volume overload decreases the contractility of both right and left ventricles and is associated with oxidative stress in both ventricles. These results support the hypothesis that oxygen free radicals are involved in the chronic volume overload-induced cardiac depression.
Descriptors: animal care, biochemistry and molecular biophysics, cardiovascular system, transport and circulation, cell biology, metabolism.

Pua, E.C., S.F. Idriss, P.D. Wolf, and S.W. Smith (2007). Real-time three-dimensional transesophageal echocardiography for guiding interventional electrophysiology: feasibility study. Ultrasonic Imaging 29(3): 182-94. ISSN: 0161-7346.
Abstract: At present, there are limited methods of acquiring three-dimensional visualization of cardiac structure and function in real-time during interventional electrophysiology procedures. Images acquired for integration of computerized tomography and magnetic resonance imaging with electroanatomic mapping systems are static and are obtained earlier in time. The purpose of this study was to test the feasibility of real-time three-dimensional transesophageal echocardiography for the guidance of interventional electrophysiological studies. A matrix array transducer with 504 channels operating at 5 MHz in a 1 cm diameter steerable esophageal probe was used in conjunction with a scanner capable of real-time 3D scanning of pyramidal volumes from 65 degrees to 120 degrees at rates up to 30 volumes per second. This device has a spatial resolution of approximately 3 mm at 5 cm depth. The authors acquired real-time three-dimensional images of anatomic landmarks of value for electrophysiological procedures in five closed chest canines. Real-time, three-dimensional ultrasound imaging was also used for visualization and guidance of interventional catheter devices within the canine heart. Real-time three-dimensional images of the atria, pulmonary veins, and coronary sinus were acquired. Real-time 3-D color flow Doppler was employed to confirm patency. Multiple image planes of image volumes and rendered views were used to track catheter position and orientation. Images of left veno-atrial junctions have been confirmed by dissection. This study has demonstrated the feasiblity of using real-time three-dimensional transesophageal echocardiography for guiding interventional electrophysiology. The technology has the potential to fill a niche as an adjunct modality for cost-effective real-time interventional guidance and assessment, providing catheter and pacing lead visualization simultaneously with functional volumetric cardiac imaging.
Descriptors: echocardiography, transesophageal, heart catheterization methods, imaging, three dimensional, ultrasonography, interventional, coronary sinus ultrasonography, dogs, feasibility studies, heart atria ultrasonography, models, animal, pulmonary veins ultrasonography, ultrasonography, doppler, color.

Quail, A., S.A. Mcilveen, D. Cottee, and S.W. White (2003). Tonic cardiac afferent control of airways blood flow in awake dogs. FASEB Journal 17(4-5): Abstract No. 558.11. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: vagal and sympathetic afferents, cardiovascular system, transport and circulation, nervous system, neural coordination, respiratory system, respiration, aortic pressure, bronchial flow, central venous pressure, heart rate.

Ramakers, C., M.A. Vos, P.A. Doevendans, M. Schoenmakers, Y.S. Wu, S. Scicchitano, A. Iodice, G.P. Thomas, C. Antzelevitch, and R. Dumaine (2003). Coordinated down-regulation of kcnq1 and kcne1 expression contributes to reduction of iks in canine hypertrophied hearts. Cardiovascular Research 57(2): 486-496. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: Objective: In animal models of hypertrophy, electrical remodeling giving rise to QT prolongation occurs rapidly and is associated with the development of torsade de pointes (TdP) arrhythmias and sudden death. Chronic AV block (CAVB)-induced hypertrophy in dogs has been associated with a reduction in the slow component (IKs) of the delayed rectifier potassium current (Ikappa), which contributes to a prolongation of ventricular repolarization, the development of an acquired form of long QT, and the substrate for triggered activity and TdP. The present study was designed to probe the molecular basis for the decrease in IKs by studying the characteristics of KCNE1 and KCNQ1, the putative genes responsible for formation of the channel. Methods and Results: Using a combination of Northern blot, competitive multiplex PCR and immunoblot assays, we found that CAVB reduces KCNE1 and KCNQ1 RNA in the canine ventricles by 70 and 80%, respectively. Protein levels of KCNE1 and KCNQ1 were reduced by 60 and 50%, respectively. We also demonstrate at the molecular level the basis for inter-ventricular difference in IKs density previously reported in hearts of normal dogs and show the basis for reduction of this difference in the CAVB dog. Conclusions: Our results indicate that the CAVB-induced reduction in IKs is due to a down-regulation of KCNE1 and KCNQ1 transcription. The data suggest that electrical remodeling of the cardiac ventricle during hypertrophy involves regulation of the gene expression through modulation of transcriptional and translational regulatory pathways. The reduction in KCNE1 and KCNQ1 expression increases the dependence of ventricular repolarization on the rapid component of Ikappa and may potentiate the action of Class III antiarrhythmic agents.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, genetics, arrhythmia, heart disease, torsades de pointes, qt prolongation, sudden death.

Riou, L.M., C. Ghezzi, G. Vanzetto, A. Broisat, J.P. Mathieu, R. Bontron, R. Pasqualini, and D. Fagret (2003). Verapamil does not inhibit 99mtcn-noet uptake in situ in normal or ischemic canine myocardium. Journal of Nuclear Medicine 44(6): 981-987. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Abstract: Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) (99mTc) (99mTcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. 99mTcN-NOET cellular uptake has been shown to be inhibited by the calcium channel inhibitor verapamil in cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ 99mTcN-NOET myocardial uptake remains unknown. Therefore, the aim of this study was to evaluate whether the inhibitory effect of verapamil on the cellular uptake of 99mTcN-NOET shown in vitro could be reproduced in situ in a canine model of normal and ischemic myocardium. Methods: 99mTcN-NOET uptake in normal and ischemic myocardium (70% flow reduction in the left anterior descending coronary artery) was measured in the absence or presence of verapamil (0.015 mg/kg/minX10 min) in anesthetized, open-chest dogs (n=17). Control animals were infused with adenosine (0.2 mg/kg/min) to match the verapamil-induced increase in flow. Results: By verapamil treatment, a clinically relevant plasma concentration of the calcium channel inhibitor was attained (mean+-SEM, 290+-152 ng/mL). In normal myocardium (n=8), regional blood flow at the time of 99mTcN-NOET injection was not statistically different in verapamil- and adenosine-treated dogs (1.69+-0.03 vs. 1.61+-0.04 mL/min/g, respectively). 99mTcN-NOET uptake was slightly higher in the presence of verapamil (0.39+-0.01 vs. 0.38+-0.01 counts per minute (cpm)/(Bq/kg)/g for adenosine; P=0.04). However, no significant difference in 99mTcN-NOET myocardial uptake was observed after normalization of the tracer uptake to regional myocardial blood flow. In ischemic myocardium (n=9), regional blood flow was lower in verapamil-treated than in adenosine-treated animals (0.22+-0.02 vs. 0.29+-0.03 mL/min/g; P<0.05). 99mTcN-NOET uptake in the ischemic area was not inhibited by verapamil (0.09+-0.01 vs. 0.10+-0.01 cpm/(Bq/kg)/g; P=not significant). Conclusion: Verapamil does not inhibit 99mTcN-NOET uptake in situ in normal and ischemic canine myocardium. These results suggest that verapamil should not affect 99mTcN-NOET myocardial uptake in patients referred for myocardial perfusion imaging.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, radiation biology, myocardial ischemia, heart disease, vascular disease.

Rivard, L., H. Sinno, A. Shiroshita Takeshita, G. Schram, T.K. Leung, and S. Nattel (2007). The pharmacological response of ischemia-related atrial fibrillation in dogs: evidence for substrate-specific efficacy. Cardiovascular Research 74(1): 104-13. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: OBJECTIVE: Acute atrial ischemia produces a substrate for atrial fibrillation (AF) maintenance, but the response of this substrate to antiarrhythmic-drugs has not been defined. The present study assessed the effects of class 1-4 antiarrhythmic-drugs on the electrophysiological consequences of acute atrial ischemia, and compared effects in ischemic AF with those in vagal AF. METHODS AND RESULTS: Isolated atrial ischemia was created by ligating a right coronary artery branch perfusing the right atrial free wall. Experiments were performed in dogs treated with loading and maintenance doses of flecainide (class 1; n=5), nadolol (class 2, n=7), dofetilide (class 3, n=5), or diltiazem (class 4, n=7) prior to coronary artery occlusion. Dogs subjected to coronary occlusion without pre-treatment (n=10) served as controls. Coronary artery occlusion substantially increased AF duration, e.g. from 7+/-4 s (pre-ischemic baseline) to 876+/-245 s at 3 h of ischemia, and caused substantial ischemic zone conduction slowing. Diltiazem and nadolol prevented AF promotion (AF durations 12+/-8 s and 4+/-1 s at 3 h of ischemia respectively; each p<0.001 vs control) and suppressed ischemic conduction slowing. Flecainide and dofetilide failed to prevent ischemia-induced AF promotion (e.g. AF duration at 3-hour ischemia 779+/-417 and 801+/-414 respectively, p=NS vs control) and failed to alter ischemia-induced conduction slowing. A different pattern of response occurred with vagal AF: flecainide was highly effective in reducing vagal AF duration; dofetilide, diltiazem, and nadolol were ineffective. CONCLUSIONS: Beta-blockade and Ca(2+) antagonism suppress the arrhythmic consequences of acute atrial ischemia, whereas Na(+) channel or K(+)-channel block are ineffective. These results are relevant to understanding the effects of different classes of antiarrhythmic-drugs on AF occurring in coronary disease patients.
Descriptors: anti arrhythmia agents therapeutic use, atrial fibrillation prevention and control, coronary disease drug therapy, flecainide therapeutic use, adrenergic beta antagonists therapeutic use, atrial fibrillation etiology, calcium channel blockers therapeutic use, coronary disease complications, diltiazem therapeutic use, dogs, electric stimulation, models, animal, nadolol therapeutic use, phenethylamines therapeutic use, potassium channel blockers therapeutic use, refractory period, electrophysiological drug effects, sodium channel blockers therapeutic use, sulfonamides therapeutic use, vagus nerve.

Rosenthal, D., E.D. Wellons, F.W. Shuler, A.B. Levitt, and V.J. Henderson (2004). Retrohepatic vena cava and hepatic vein injuries: a simplified experimental methods of treatment by balloon shunt. Journal of Trauma Injury Infection and Critical Care 56(2): 450-452. ISSN: 1079-6061.
Descriptors: cardiovascular system, transport and circulation, digestive system, ingestion and assimilation, methods and techniques, hepatic vein injury, digestive system disease, injury, vascular disease, diagnosis, surgery, retrohepatic vena cava injury, digestive system disease, injury, vascular disease, diagnosis, surgery, balloon shunt, clinical techniques, therapeutic and prophylactic techniques, hepatic lobectomy, experimental surgical techniques, laboratory techniques, risk assessment, survival rate.

Rowell, L.B. (2007). Human experimentation: no accurate, quantitative data? Journal of Applied Physiology 102(3): 837-40. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Descriptors: cardiovascular physiological phenomena, human experimentation, models, animal, blood volume physiology, body temperature regulation physiology, cats, dogs, exercise physiology, posture physiology, regional blood flow physiology, renal circulation physiology, research design, rheology methods, species specificity.
Notes: Comments: Comment On: J Appl Physiol. 2006 Oct;101(4):1264-5; discussion 1265-6, 1270.

Rozman, J. and S. Ribaric (2007). Selective recording of electroneurograms from the left vagus nerve of a dog during stimulation of cardiovascular or respiratory systems. Chinese Journal of Physiology 50(5): 240-50. ISSN: 0304-4920.
Abstract: Selective electroneurograms (ENGs) from superficial regions of the left vagus nerve of a dog were recorded with a 33-electrode spiral cuff (cuff) implanted on the nerve at the neck in an adult Beagle dog. The electrodes in the cuff were arranged in thirteen groups of three electrodes (GTE 1-13). To identify the relative positions of the particular nerve regions that innervated the heart and lungs, stimulating pulses (2 mA, 200 micros, 20 Hz) were individually delivered to all thirteen GTEs. It was shown that by delivering stimulating pulses to GTEs 4 and 9, heart rate, blood pressure and respiratory rate were modulated. Precisely, only when the stimuli were delivered to GTE 9, the heart rate began to fall and only when the stimuli were delivered to GTE 4 the rate of breathing decreased. To test the selectivity of recording the above-defined groups GTEs 4 and 9 and randomly chosen GTEs 1 and 7 were simultaneously used as recording GTEs while cardio-vascular or respiratory systems were stimulated by carotid artery compression, epinephrine injection and non-invasive, positive end-pressure ventilation. Results showed that stimulations elicited site-specific changes in ENG power spectra recorded from the superficial regions of the vagus nerve. Power spectrum of the ENG recorded with GTE 9, contained frequencies belonging to the neural activity elicited by compression of the carotid artery and injection of epinephrine. The power spectrum of the ENG recorded with GTE 4, contained frequencies belonging to the neural activity elicited by non-invasive, positive end-expiratory pressure ventilation. We concluded that the multi-electrode nerve cuff enables selective stimulation and recording of nerve activity from internal organs.
Descriptors: cardiovascular system drug effects, electrodiagnosis instrumentation, electrodiagnosis methods, respiratory system drug effects, vagus nerve physiology, blood pressure drug effects, dogs, electric impedance, electric stimulation, electrodes, electrophysiology, epinephrine pharmacology, heart rate drug effects, models, animal, sensitivity and specificity, vagus nerve anatomy and histology.

Ruiz, M., K. Takehana, F.D. Petruzella, D.D. Watson, G.A. Beller, and D.K. Glover (2002). Arbutamine stress perfusion imaging in dogs with critical coronary artery stenoses: 99mtc-sestamibi versus 201tl. Journal of Nuclear Medicine 43(5): 664-670. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Abstract: Having previously shown that dobutamine reduces 99mTc-methoxyisobutylisonitrile (sestamibi (MIBI)) uptake in normal myocardium by elevating intracellular calcium, we hypothesized that arbutamine, which has less inotropic effect than dobutamine, might cause less reduction in MIBI uptake, thereby improving defect contrast. In this study using a canine model, we compared the effects of arbutamine stress on myocardial blood flow, myocardial MIBI uptake, and systolic thickening in the presence of a coronary artery stenosis. Methods: Arbutamine was infused (0.5-250 ng/kg/min) in 8 open-chest dogs with critical coronary stenoses that abolished flow reserve. At the time of peak arbutamine effect, MIBI (296 MBq), 201Tl (27.75 MBq), and microspheres were coinjected. The dogs were killed 5 min later, and myocardial tracer activities and flow were quantified by well counting. Ex vivo imaging of heart slices was also performed. Results: Arbutamine increased mean heart rate, peak positive left ventricular pressure and its first time-derivative, and normal-zone myocardial thickening. Stenotic zone flow and thickening did not increase during arbutamine infusion. MIBI uptake versus flow was significantly lower than 201Tl uptake at the same flow values. By imaging, defect magnitude (stenotic/normal) was greater for 201Tl than MIBI (0.56 vs. 0.57; P<0.001). Conclusion: In the presence of coronary stenoses that abolished regional flow reserve, myocardial uptake of MIBI, compared with 201Tl, significantly underestimated the arbutamine-induced flow heterogeneity. The attenuation of MIBI uptake and diminished defect contrast during arbutamine stress were comparable with those previously reported for dobutamine stress.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, radiation biology, systolic thickening, heart disease, 201 thallium sestamibi imaging, analytical method, imaging method, 99m technetium sestamibi imaging, arbutamine stress perfusion imaging, defect contrasts, flow reserve, left ventricular pressure, stenotic zone flow.

Saba, D., M. Yilmaz, H. Yavuz, S. Noyan, B. Avci, A. Ercan, H. Ozkan, and M. Cengiz (2007). Sutureless vascular anastomoses by N-butyl-2 cyanoacrylate adhesive: an experimental animal study. European Surgical Research; Europaische Chirurgische Forschung; Recherches Chirurgicales Europeennes 39(4): 239-44.
Abstract: BACKGROUND: The purpose of this animal study was to find out whether sutureless anastomoses using N-butyl-2-cyanoacrylate were effective in the suppression of neointimal hyperplasia or not. MATERIAL AND METHODS: Ten male adult mongrel dogs were used in this animal study. The animals were randomly divided into a control group (n = 5) and a study group (n = 5). The study group underwent sutureless anastomoses using N-buthyl-2-cyanoacrylate adhesive. Infrarenal aortoaortic graft was interposed using polytetrafluoroethylene. RESULTS: In the study group, the mean intimal thickness at the proximal anastomosis was 27.4 +/- 1.94 microm and 27.4 +/- 1.51 microm at the distal anastomosis. In the control group, the mean intimal thickness was 138.4 +/- 5.02 mum at the proximal anastomosis and 67.6 +/- 6.42 microm at the distal anastomosis. Intimal thickness at the proximal and distal anastomoses in the control group was significantly (p < 0.001) greater than in the study group. Also, perianastomotic inflammation was more obvious in the control group compared to the study group (p < 0.01). CONCLUSION: Sutureless anastomoses using with N-butyl-2-cyanoacrylate adhesive might be a good alternative to conventional suture technique. Copyright 2007 S. Karger AG, Basel.
Descriptors: anastomosis, surgical methods, aorta surgery, enbucrilate analogs and derivatives, tissue adhesives pharmacology, vascular surgical procedures methods, aorta pathology, dogs, enbucrilate pharmacology, hyperplasia, models, animal, sutures, tunica intima pathology.

Sakuragi, T., Y. Okazaki, M. Mitsuoka, and T. Itoh (2008). Dramatic hemostasis of the transected pulmonary artery model using SOFT COAG electrosurgical output. Interactive Cardiovascular and Thoracic Surgery 7(5): 764-6.
Abstract: We report the use of low-voltage, automatically regulated, electrosurgical coagulation to seal the bleeding from pulmonary arteries inadvertently during surgical intervention. Conventional electrosurgical coagulation uses high voltage, which generates intensive heat in the tissue. The heat results in carbonized eschar formation that can be easily broken by mechanical stress and lead to postoperative bleeding. SOFT COAG output automatically regulates the output voltage to a maximum of 200 Volts, preventing the generation of sparking. Thus, there is no formation of carbonized eschar. The instrument generates Joule heat alone in the tissue and the temperature rises to below boiling point, which effectively coagulates protein. Initial experiments, using a beagle model, clearly demonstrated the effectiveness and reliability of sealing both macroscopically and histopathologically. SOFT CAOG can be easily adopted both in open thoracotomy as well as in thoracoscopic procedures.
Descriptors: blood loss, surgical prevention and control, electrocoagulation instrumentation, hemostasis, surgical methods, pulmonary artery injuries, pulmonary artery surgery, automation, dogs, equipment design, hemostasis, surgical instrumentation, models, animal, pneumonectomy, pulmonary artery pathology, time factors.

Sander, M., K.L.K. Welling, J.B. Ravn, B. Boberg, and O. Amtorp (2003). Endogenous no does not regulate baseline pulmonary pressure, but reduces acute pulmonary hypertension in dogs. Acta Physiologica Scandinavica 178(3): 269-277. ISSN: 0001-6772.
NAL Call Number: QP1.A2
Abstract: It has remained unclear whether endogenous production of nitric oxide (NO) plays an important role in the regulation of physiologically normal pulmonary pressures. Severe alveolar hypoxia is accompanied by decreased pulmonary NO production, which could contribute to the development of hypoxic pulmonary hypertension. On the other hand, pharmacological NO inhibition further augments this hypertensive response. Aims: The aims of the present study were to test: (a) whether NO contributes importantly in the maintenance of baseline pulmonary pressure; and (b) to which degree NO is involved in the pulmonary haemodynamic adjustments to alveolar hypoxia. Methods: In anaesthetized dogs (n=37), the systemic and pulmonary haemodynamic effects of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1) and substrate, L-arginine (200-500 mg kg-1), were determined at baseline and during alveolar hypoxia. Constant blood flows were accomplished by biventricular bypass, and systemic normoxaemia was maintained by extracorporeal oxygenation. Results: The primary findings were: (a) L-NAME failed to increase baseline mean pulmonary arterial pressure (10.1+-0.7 vs. 10.5+-0.5 mmHg, P=ns), despite effective NO synthase inhibition as evidenced by robust increases in systemic arterial pressures; (b) L-NAME augmented the pulmonary hypertensive response to alveolar hypoxia (10.2+-0.7 to 19.5+-1.7 with L-NAME vs. 9.9+-1.1 to 15.5+-1.0 mmHg without L-NAME, P<0.05); and (c) L-arginine failed to decrease baseline or elevated pulmonary pressures. Instead, prolonged L-arginine caused increases in pulmonary pressure. Conclusion: These findings suggest that NO plays no significant role in the tonic physiological control of pulmonary pressure, but endogenous NO becomes an important vasodilatory modulator during elevated pulmonary pressure.
Descriptors: cardiovascular system, transport and circulation, respiratory system, respiration, acute pulmonary hypertension, vascular disease, alveolar hypoxia, respiratory system disease, baseline pulmonary pressure.

Satoh, Y., A. Sugiyama, A. Takahara, K. Chiba, and K. Hashimoto (2004). Electropharmacological and proarrhythmic effects of a class iii antiarrhythmic drug nifekalant hydrochloride assessed using the in vivo canine models. Journal of Cardiovascular Pharmacology 43(5): 715-723. ISSN: 0160-2446.
Abstract: Cardiovascular effects of Nifekalant were examined using halothane-anesthetized dogs, and its proarrhythmic potential was estimated with chronic complete atrioventricular block dogs. Nifekalant was intravenously administered to the halothane-anesthetized dogs in three doses of 0.03, 0.3, and 3 mg/kg/ 10 minutes with a pause of 20 minutes (n = 6). The low dose hardly affected any of the cardiovascular parameters. The middle dose, a clinically recommended antiarrhythmic dose, decreased the total peripheral resistance, increased the cardiac output, and prolonged the ventricular repolarization phase and effective refractory period. The high dose increased the left ventricular contraction, transiently decreased the mean blood pressure, and enhanced the atrioventricular conduction, besides potentiation of the changes induced by the middle dose. Increment in the repolarization phase by the high dose was greater than that in the refractoriness, leading to increase of ventricular electrical vulnerability. To the atrioventricular block animals, clinically relevant antiarrhythmic dose of 3 mg/kg p.o. of Nifekalant and its 10-times-higher dose were administered. The high dose prolonged QT interval leading to torsades de pointes in all animals (n = 5), which was not detected by the clinical dose (n = 5). These results suggest that antiarrhythmic dose of Nifekalant can be used safely; however, caution should be paid for patients complicating bradycardia and/or a risk of elevated plasma drug concentration.
Descriptors: cardiovascular system, transport and circulation, pharmacology, torsades de pointes, heart disease, atrioventricular conduction, cardiac output, chronic complete atrioventricular block, effective refractory period, left ventricular contraction, mean blood pressure, monophasic action potential, prolonged qt interval, refractoriness, total peripheral resistance, ventricular electrical vulnerability, ventricular repolarization phase.

Satoh, Y., A. Sugiyama, K. Wada, H. Nomura, and K. Hashimoto (2004). In vivo electropharmacological effects of a class iii antiarrhythmic drug dl-sotalol assessed using halothane anesthetized canine model. 77th Annual Meeting of the Japanese Pharmacological Society, Osaka, Japan; March 08-10, 2004,Vol. 94(Supplement 1): 265P,
Descriptors: cardiovascular system, transport and circulation, pharmacology, veterinary medicine, medical sciences, hypotension, vascular disease, blood pressure, left ventricular contraction, ventricular repolarization.

Schneider, A., M. Chandra, G. Lazarovici, I. Vlodavsky, G. Merin, G. Uretzky, J.B. Borman, and H. Schwalb (1997). Naturally produced extracellular matrix is an excellent substrate for canine endothelial cell proliferation and resistance to shear stress on ptfe vascular grafts. Thrombosis and Haemostasis 78(5): 1392-1398. ISSN: 0340-6245.
Abstract: Purpose: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. Methods: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 X 0.6 cm), PTFE graft precoated with fibronectin (IN), or PTFE precoated with FN and a naturally produced ECM (106 cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preceded ECM coated grafts were implanted in the common carotid arteries of dogs. Results: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significantly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. Conclusion: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.
Descriptors: cardiovascular system, transport and circulation, equipment apparatus devices and instrumentation, polytetrafluoro ethylene vascular graft, prosthetic, shear stress.

Schwartz, L.M., R.B. Jennings, and K.A. Reimer (1995). Minimum ischemic stress required for myocardial preconditioning in dogs: effect of analgesia, using the opiate agonist-antagonist, butorphanol. FASEB Journal 9(3): A299. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, pharmacology, meeting abstract, pentobarbital.

Sharifov, O.F., V.V. Fedorov, G.G. Beloshapko, A.V. Glukhov, A.V. Yushmanova, and L.V. Rosenshtraukh (2004). Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs. Journal of the American College of Cardiology 43(3): 483-490. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES We studied the effects of beta-adrenergic and cholinergic stimulation and blockade on spontaneous atrial fibrillation (AF) in the intact dog heart. BACKGROUND Paroxysmal AF is often preceded by changes in autonomic tone, but the relative roles of adrenergic and cholinergic influences on AF induction are not well known. METHODS Perfusion of catecholamines and acetylcholine (ACh), as well as their combination, through the sinus node artery was used to induce AF in 20 anesthetized open-chest dogs without electrical stimulation of atria. RESULTS Isoproterenol and adrenaline (10 to 100 mumol/l) induced AF in 21% (3 of 14) and 17% (1 of 6) of dogs, respectively. Atropine (1 to 2 mg) treatment prevented catecholamine-mediated AF, indicating a critical role of cholinergic tone in these AF episodes. Acetylcholine (2.8 +- 0.3 mumol/l) induced AF in all dogs. Beta-blockade by propranolol (1 mg/kg) did not prevent ACh-induced AF, but increased the threshold ACh concentration for AF induction to 23.5 +- 3.4 mumol/l (p < 0.05). Acetylcholine-mediated AF was facilitated by isoproterenol (1 to 2 and 10 mumol/l), which decreased the threshold ACh concentration for AF induction to 0.5 +- 0.1 and 0.4 +- 0.1 mumol/l, respectively (p < 0.05) and increased the AF duration (from 25 +- 7 to 141 +- 54 and 233 +- 60 s, respectively; p < 0.05). Epicardial mapping of the right atrium (112 unipolar electrodes) demonstrated similar activation patterns during arrhythmias induced by ACh and catecholamines. CONCLUSIONS These data indicate that although both autonomic systems play a role in AF, cholinergic stimulation is likely the main factor for spontaneous AF initiation in this animal model. Adrenergic tone modulates the initiation and maintenance of cholinergically mediated AF.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology, spontaneous atrial fibrillation, heart disease, adrenergic stimulation, cholinergic stimulation.

Shen, Y.T., J.J. Mallee, L.K. Handt, D.B. Gilberto, J.J.J. Lynch, R.J. Hargreaves, K.S. Koblan, R.J. Gould, and S.A. Kane (2003). Effects of inhibition of alpha-cgrp receptors on cardiac and peripheral vascular dynamics in conscious dogs with chronic heart failure. Journal of Cardiovascular Pharmacology 42(5): 656-661. ISSN: 0160-2446.
Abstract: Whether endogenous calcitonin gene-related peptide (CGRP) plays a role in heart failure is unclear. Seven dogs were instrumented with left ventricular (LV) pressure gauges, pacers, coronary occluder and aortic, atrial, and coronary sinus catheters. Hemodynamic recordings and response to alpha-CGRP challenge were obtained for baseline in the conscious state. Rapid pacing (240 beats/min) was then initiated. The coronary artery was occluded for 90 minutes followed by reperfusion after 2 weeks of pacing. After 6 weeks of pacing, LV pressure (-11+-6%), LV dP/dt (-53+-5%), and mean arterial pressure (-15+-4%) decreased (P<0.01), while left atrial pressure (+19+-3 mm Hg from 7+-1 mm Hg) and heart rate (+53+-16%) increased (P<0.01). Infusion of the alpha-CGRP receptor antagonist alpha-CGRP(8-37) (30 mug/kg/min, iv), which blocked the exogenous alpha-CGRP challenge, did not affect any of these indices. Regional blood flow, as measured by the microsphere technique, in the nonischemic myocardium, as well as cerebral and renal vasculatures were unaltered during the infusion of alpha-CGRP(8-37). Plasma concentrations of CGRP from both arterial and coronary sinus samples were unchanged after 6 weeks of pacing as compared with control. Thus, we conclude that endogenous alpha-CGRP does not appear to play a major role in the regulation of cardiac and peripheral vascular dynamics in the late stage of heart failure.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, methods and techniques, chronic heart failure, heart disease, cardiac vascular dynamics, peripheral vascular dynamics.

Shi, H., H. Wang, D. Li, S. Nattel, and Z. Wang (2004). Differential alterations of receptor densities of three muscarinic acetylcholine receptor subtypes and current densities of the corresponding k+ channels in canine atria with atrial fibrillation induced by experimental congestive heart failure. Cellular Physiology and Biochemistry 14(1-2): 31-40. ISSN: 1015-8987.
NAL Call Number: QH573.C455
Abstract: Parasympathetic tone and congestive heart failure (CHF) are two of promoting factors in initiation and perpetuation of atrial fibrillation (AF). Recent studies indicate co-existence of multiple muscarinic acetylcholine receptor Subtypes (mAChRs) that mediate several distinct K+ currents in the heart; inward rectifier K+ current IKACh by the M2, and two delayed rectifier K+ currents IKM3 and IK4AP by the M3 and M4 receptors, respectively. We studied the alterations of atrial mAChRs and their coupled K+ channels in the setting of AF in dogs with ventricular tachypacing-induced CHF. Whole-patch-clamp recordings showed that the current densities of IKACh (induced by 1 mM acetylcholine) and IK4AP (induced by 1 mM 4-aminopyridine) were apprx45% and apprx55% lower, respectively, while that of IKM3 (induced by 10 mM choline) was apprx75% higher, at a plateau voltage of 0 mV in atrial myocytes from CHF than those from healthy hearts. In healthy hearts, IKACh comprised >60%, and IKM3 and IK4AP<30%, of the total outward K+ currents mediated by mAChRs at depolarized potentials (between -20 mV and +50 mV). In AF atria of CHF dogs, however, the contribution of IKM3 increased to apprx50%, exceeding those of IKACh or IK4AP. Western blot analyses with atrial membrane protein samples indicated that receptor densities of the M2 and M4 subtypes decreased by apprx33% and apprx22%, respectively, whereas that of the M3 subtype increased by apprx2.3 folds, in parallel to the alterations of the corresponding K+ currents. We conclude that differential alterations of mAChR subtypes underlie differential alterations of their coupled K+ channels in AF atria and these differential alterations may contribute to atrial remodeling in AF induced in the setting of CHF.
Descriptors: cardiovascular system, transport and circulation, atrial fibrillation, heart disease, experimental congestive heart failure, western blot, genetic techniques, laboratory techniques, patch clamp recording, histology and cytology techniques.

Shimizu, J., S. Mohri, G. Iribe, Y. Kitagawa, H. Ito, J. Araki, M. Takaki, and H. Suga (2003). Postextrasystolic contractility normally decays in alternans in canine in situ heart. Japanese Journal of Physiology 53(4): 313-318. ISSN: 0021-521X.
NAL Call Number: QP34.5.J3
Abstract: We have reported that the postextrasystolic (PES) potentiation of left ventricular (LV) contractility usually decays in alternans at heart rates above 80-100 beats/min in the canine excised, cross-circulated heart. We examined whether the PES contractility would also decay in alternans even in the canine in situ heart presumably more physiological than the excised heart. In anesthetized, ventilated, and open-chest mongrel dogs, we measured LV pressure and volume with a micromanometer and a conductance catheter cannulated into the LV and obtained LV end-systolic maximum elastance (Emax) as the reasonably load-independent contractility index. We inserted an extrasystole followed by a compensatory pause into steady-state regular beats at heart rates above 90 beats/min and analyzed the PES decay pattern of Emax. We found that Emax potentiated in the first PES beat decayed in alternans within 5-6 PES beats. This indicates that PES contractility also decays in alternans in the normal canine in situ heart.
Descriptors: cardiovascular system, transport and circulation, arrhythmia, heart disease, alternans decay, calcium recirculation, compensatory pause, left ventricular contractility, postextrasystolic potentiation, left ventricular end systolic maximum elastance, postextrasystolic contractility, pressure volume loop.

Shiroshita Takeshita, A., B.J. Brundel, B. Burstein, T.K. Leung, H. Mitamura, S. Ogawa, and S. Nattel (2007). Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure. Cardiovascular Research 74(1): 75-84. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: BACKGROUND: Congestive heart failure (CHF) is a common cause of atrial fibrillation (AF). Oxidative stress and inflammation (profibrotic) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha, antifibrotic) factors may be involved in CHF-related remodeling. We evaluated the effects of simvastatin (antioxidant, anti-inflammatory) and fenofibrate (PPAR-alpha activator) on CHF-related atrial remodeling. METHODS AND RESULTS: Dogs were subjected to 2-week ventricular tachypacing (VTP) in the absence and presence of simvastatin (20 or 80 mg/day) or fenofibrate. Induced AF duration (DAF) was increased by VTP from 36+/-14 (non-paced controls) to 1005+/-257 s (p<0.01). Simvastatin prevented VTP-induced DAF increases (147+/-37 and 84+/-37 s at 20 and 80 mg/day, respectively), but fenofibrate did not (1018+/-352 s). Simvastatin also attenuated CHF-induced conduction abnormalities (heterogeneity-index reduced from 1.5+/-0.1 to 1.1+/-0.1 and 1.0+/-0.1 at 20 and 80 mg/day, p<0.01) and atrial fibrosis (from 19.4+/-1.3% to 10.8+/-0.8% and 9.9+/-0.8% at 20 and 80 mg/day, p<0.01), while fenofibrate did not. Simvastatin (but not fenofibrate) also attenuated VTP-induced left-ventricular nitric-oxide synthase and nitrotyrosine increases, along with hemodynamic dysfunction. Atrial fibroblast proliferation increased with 24-h fetal bovine serum (FBS) stimulation from 654+/-153 to 7264+/-1636 DPM (p<0.001). Simvastatin, but not fenofibrate, suppressed fibroblast proliferation (664+/-192 DPM, p<0.001). Simvastatin also significantly attenuated transforming growth factor-beta1-stimulated alpha-smooth muscle actin (alpha-SMA) expression (indicating myofibroblast differentiation) from 1.3+/-0.1 to 1.0+/-0.1 times baseline (p<0.05). CONCLUSIONS: CHF-induced atrial structural remodeling and AF promotion are attenuated by simvastatin, but not fenofibrate. Statin-induced inhibition of profibrotic atrial fibroblast responses and attenuation of left-ventricular dysfunction may contribute to preventing the CHF-induced fibrotic AF substrate.
Descriptors: anti inflammatory agents therapeutic use, atrial fibrillation prevention and control, heart failure drug therapy, simvastatin therapeutic use, actins analysis, antilipemic agents therapeutic use, atrial fibrillation etiology, biological markers analysis, cardiac pacing, artificial, cell proliferation drug effects, cells, cultured, dogs, fibroblasts drug effects, heart atria chemistry, heart failure complications, heart ventricles chemistry, models, animal, nitric oxide synthase type ii analysis, nitric oxide synthase type iii analysis, ppar alpha agonists, procetofen therapeutic use, refractory period, electrophysiological drug effects, tyrosine analogs and derivatives, tyrosine analysis, ventricular remodeling drug effects.
Notes: Comment In: Cardiovasc Res. 2007 Apr 1;74(1):8-10.

Silva, G.V., S. Litovsky, J.A.R. Assad, A.L.S. Sousa, B.J. Martin, D. Vela, S.C. Coulter, J. Lin, J. Ober, W.K. Vaughn, R.V.C. Branco, E.M. Oliveira, R. He, Y.J. Geng, J.T. Willerson, and E.C. Perin (2005). Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111(2): 150-156. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background - Bone marrow - derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking. Methods and Results - Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100 x 106 MSCs/10 mL saline) ( n = 6) or saline only (10 mL) (controls) (n = 6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes. Conclusions - In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, ischemic heart disease, therapy, ameroid constrictor placement, laboratory techniques, echocardiography, clinical techniques, diagnostic techniques, imaging and microscopy techniques, left ventricular ejectin fraction.

Sleph, P.G., K.K. Sadanaga, D.E. Burkett, C.S. Parham, R.J. Scalese, and G.J. Grover (2003). Effect of mitochondrial katp activation on necrosis in an isolated gracilis model of ischemia and reperfusion in dogs. FASEB Journal 17(4-5): Abstract No. 150.5. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, muscular system, movement and support, pharmacology, ischemia reperfusion, reperfusion injury, vascular disease, necrosis.

Spaan, J.A., S. Dekker, D.S. Fokkema, I. Vergroesen, and H. Vink (2001). Shear stress induced endothelial no release in canine coronary circulation is attenuated by the glycocalyx. Circulation 104(17 Supplement): II.302 II.303. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, blood flow conductance, peak reactive hyperemia, shear stress, meeting abstract.

Stambler, B.S., G. Fenelon, R.K. Shepard, H.F. Clemo, and C.M. Guiraudon (2003). Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. Journal of Cardiovascular Electrophysiology 14(5): 499-507. ISSN: 1045-3873.
Abstract: Atrial Tachycardia in Heart Failure. Introduction: Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing. Methods and Results: Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After 20 +- 7 days of rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length 120 +- 12 msec) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (ltoreq 130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400- and 300-msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization. Conclusions: CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD-induced triggered activity resulting from intracellular calcium overload.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, arrhythmia, heart disease, atrial tachycardia, congestive heart failure, rapid ventricular pacing.

Stepp, D.W., Y. Nishikawa, and W.M. Chilian (1999). Regulation of shear stress in the canine coronary microcirculation. Circulation 100(14): 1555-1561. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background: Physical forces, such as pressure and flow, are well known to affect vascular function in the coronary circulation. Increases in shear stress produce vasodilation in coronary arterioles in vitro, and constant-flow preparations suggest a role for shear stress-induced vasodilation during adjustments to metabolic demand in vivo. Hypothetically, the regulation of shear stress can be viewed as a negative feedback control scheme (increased velocity fwdarw increased shear fwdarw vasodilation fwdarw decreased velocity fwdarw shear normalized). Therefore, we hypothesized that shear stress would be at least partially regulated during conditions of elevated flow. Methods and Results: We used fluorescence microangiography to measure microvascular diameters and velocities in the coronary circulation in vivo and used these variables to calculate shear stress. Measurements were obtained under basal conditions, during maximal coronary blood flow, and after inhibition of NO synthase. Basal shear stress in the coronary circulation averaged 10 dyn/cm2 in small arteries and 19 dyn/cm2 in arterioles. Regulation of shear stress was observed in small arteries during adenosine-induced increases in coronary blood flow, but arterioles showed minimal regulation. NO synthase blockade had no effect on basal shear stress but completely abolished its regulation in small arteries during vasodilation. Conclusions: Our data provide the first quantitative estimates of microvascular shear stress in the coronary circulation. Moreover, our results suggest that shear stress in small coronary arteries is regulated by NO release from the endothelium.
Descriptors: cardiovascular system, transport and circulation, coronary microcirculation, flow force, pressure force, shear stress, nitric oxide release regulated, regulation, vascular function.

Stonerook, M., C. Hassler, P. Tosca, J. Merrill, D. Vasconcelos, and A. Smith (2003). Cardiotoxicity study of nsc-638850 (ucn-01) and cytostar (ara-c) given alone or in combination to beagle dogs. Toxicological Sciences 72(S-1): 36 ISSN: 1096-6080.
NAL Call Number: RA1190.F8
Descriptors: pharmacology, toxicology, cardiotoxicity, heart disease, toxicity, drug induced, ecg, electrocardiography, clinical techniques, diagnostic techniques, cardiovascular evaluation, combination chemotherapy, therapeutic and prophylactic techniques, blood pressure, body temperature, heart rate, necrosis, vascular resistance, venodilation.

Stuyvers, B.D., P.A. Boyden, and H.E.D.J. Ter Keurs (2004). 2d-confocal analysis of spontaneous micro ca2+-transients in canine purkinje cells. Biophysical Journal 86(1): 223A. ISSN: 0006-3495.
NAL Call Number: 442.8 B5238
Abstract: Aim: Confocal microscopy of Ca2+ using lines positioned longitudinally (LongL) in the core of unstimulated canine Purkinje cells (PCell) have shown typical Ca2+-sparks, spontaneous cell-wide waves and brief local increases of (Ca2+)i with larger amplitudes and different shapes compared to sparks. Transverse scans of Pcells (TransL) showed Ca2+-elevations propagating from the edge to the core. Our observations suggested that microCa2+ waves move from the edge to the core at varying angles (10-90deg) relative to the sarcolemma. Here, we present an analysis of the 3 dimensional dynamics of these Ca2+ events by using confocal scans at different positions in the cells and 2D-imaging of the initiation and propagation of the waves. Methods: 18 PCell aggregates were isolated from canine hearts, incubated with Fluo4-AM, superfused with Tyrode (25-30degreeC, pH 7.4, Cao=2 mM). Fluorescence of Fluo4 (F) was scanned along 25 mum lines and represented as ratio F/Fo (Fo: basal fluorescence). We visualized local Ca2+-events by confocal images (10mumX10mum; 8 frames/s). Results: LongL at varied distance from the sarcolemma showed initiation of transverse microwaves in a subsarcolemmal region (subSL: 3 to 8 mum from the sarcolemma). The combination of TransL and LongL revealed Ca2+-events propagating along the sarcolemma in the SubSL. Spark-like Ca2+-events with large amplitude (F/Fo>3) were clearly identified in the subSL. Confocal 2D-imaging of Ca2+ focused on cell edges showed microwaves that propagate within the subSL region (velocity apprx50mum/s). On their path, these SubSL occasionally initiate secondary waves that move toward the core. Conclusion: Our observations suggest a multidirectional system for Ca2+-activation in Pcells. We propose that, in Pcells, which lack t-tubules, a subSL compartment acts as an initiator of micro Ca2+ waves, which triggers major Ca2+ releases in the core compartment.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, nervous system, neural coordination, 2d confocal microscopy, two dimensional confocal microscopy, imaging and microscopy techniques, laboratory techniques.

Sugiyama, A. (2003). Effects of clinically available drugs on the repolarization process of the heart assessed by the in vivo canine models. Folia Pharmacologica Japonica 121(6): 393-400. ISSN: 0015-5691.
Abstract: The proarrhythmic effects of class III antiarrhythmic agents and non-cardiovascular drugs, which have been shown to prolong QT interval, were assessed using two types of in vivo canine models. First, electrophysiological effects of dofetilide, nifekalant, amiodarone, cisapride, astemizole, sulpiride, haloperidol, and sparfloxacin were assessed using halothane-anesthetized dogs. Each drug prolonged the monophasic action potential (MAP) duration and effective refractory period (ERP) at clinically recommended daily doses. The extent of increase was greater in the refractoriness than in the repolarization only for amiodarone, indicating abbreviation of the terminal repolarization period. The reverse was true for the other drugs. Next, torsadogenic action of sematilide, nifekalant, amiodarone, cisapride, terfenadine, sulpiride, and sparfloxacin was assessed using chronic complete atrioventricular block dogs with Holter ECG monitoring in the conscious state. Oral administration of 1-10 times higher doses than the clinically relevant doses of the drugs induced polymorphic ventricular tachycardia torsades de pointes (TdP), except for amiodarone. These results indicate that the prolongation and backward shift of the terminal repolarization period may be closely related to the drug-induced TdP and suggest that these in vivo models can be used to screen proarrhythmic potential of new drugs.
Descriptors: cardiovascular system, transport and circulation, pharmacology, veterinary medicine, medical sciences, atrioventricular block, heart block, long QT syndrome, polymorphic ventricular tachycardia, heart disease, torsades de pointes, holter ecg monitoring, holter electrocardiography monitoring, clinical techniques, diagnostic techniques, qt interval, effective refractory period [erp], monophasic action potential.
Language of Text: Japanese.

Sugiyama, A., Y. Satoh, K. Wada, H. Nomura, Y. Nakamura, and K. Hashimoto (2004). Torsadogenic action of qt-prolonging drugs, astemizole and haloperidol, assessed by the canine chronic atrioventricular block model. Journal of Pharmacological Sciences 94(Supplement 1): 151P. ISSN: 1347-8613.
Descriptors: cardiovascular system, transport and circulation, pharmacology, torsades de pointes, heart disease, toxicity, drug induced, pathology, ventricular fibrillation, holter ecg monitoring, holter electrocardiography monitoring, clinical techniques, intravenous administration, oral administration, clinical techniques, chronic atrioventricular block, effective refractory period, idioventricular automaticity, ventricular repolarization phase.

Swissa, M., S. Zhou, I. Gonzalez Gomez, C.M. Chang, A.C. Lai, A.W. Cates, M.C. Fishbein, H.S. Karagueuzian, P.S. Chen, and L.S. Chen (2004). Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death. Journal of the American College of Cardiology 43(5): 858-864. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Abstract: OBJECTIVES: We sought to develop a high-yield canine model of sudden cardiac death (SCD). BACKGROUND: Because electrical stimulation is a powerful means to elicit nerve sprouting, we hypothesize that subthreshold electrical stimulation is more effective than nerve growth factor (NGF) infusion in inducing nerve sprouting and SCD in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). METHODS: We gave subthreshold electrical stimulation to the left stellate ganglion (LSG) in six normal dogs for 41+-9 days (protocol 1) and to six dogs with MI and CAVB for 41+-29 days, while continuously monitoring their cardiac rhythm (protocol 2). We also monitored the rhythm of two dogs with MI, CAVB, and NGF infusion to the LSG and determined the ventricular nerve density in six healthy control dogs. RESULTS: In protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p<0.01). In protocol 2, there was a high magnitude of cardiac nerve sprouting in all dogs studied. Ventricular tachycardia gtoreq8 beats and gtoreq20 beats was more frequent in dogs with electrical stimulation than in dogs with NGF infusion to the LSG (36+-60 and 11+-17 vs. 4.7+-6.1 and 0.1+-0.33 episodes per day, p<0.05 and p<0.03, respectively). Four of six dogs in protocol 2 had SCD. CONCLUSIONS: Subthreshold electrical stimulation of the LSG induces cardiac nerve sprouting and sympathetic hyperinnervation and facilitates the development of a high-yield canine model of ventricular arrhythmia and SCD.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, complete atrioventricular block, heart disease, therapy, myocardial infarction, heart disease, vascular disease, therapy, sudden cardiac death, long term subthreshold electrical stimulation, clinical techniques, therapeutic and prophylactic techniques.

Syuu, Y., H. Matsubara, T. Kiyooka, S. Hosogi, S. Mohri, J. Araki, T. Ohe, and H. Suga (2001). Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog. Japanese Journal of Physiology 51(2): 231-8. ISSN: 0021-521X.
NAL Call Number: QP34.5.J3
Abstract: Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.
Descriptors: animal model, Neiguan electroacupuncture, traditional acupoints, cardiovascular function, pentobarbital, fentanyl,anesthesia, left ventricular (LV) pressure-volume (P-V) data, micromanometer catheter, mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, end-systolic pressure.

Szabo, G., P. Soos, S. Mandera, U. Heger, C. Flechtenmacher, L. Seres, Z. Zsengeller, F.U. Sack, C. Szabo, and S. Hagl (2004). Mesenteric injury after cardiopulmonary bypass: role of poly(adenosine 5'-diphosphate-ribose) polymerase. Critical Care Medicine 32(12): 2392-7. ISSN: 0090-3493.
Abstract: OBJECTIVES: To investigate the effects of the ultrapotent poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitor INO-1001 on cardiac and mesenteric function during reperfusion in an experimental model of cardiopulmonary bypass with cardioplegic arrest. DESIGN: Prospective, randomized, and blinded experimental study. SETTING: Research laboratory. SUBJECTS:: Twelve anesthetized dogs underwent cardiopulmonary bypass with hypothermic cardioplegic cardiac arrest. INTERVENTIONS: After 60 mins of hypothermic cardiac arrest, either PARP inhibitor INO-1001 (1 mg/kg, n = 6) or vehicle (control, n = 6) was administered during reperfusion. MEASUREMENTS AND MAIN RESULTS: Left ventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and mesenteric blood flow and vasodilatory responses to acetylcholine and sodium nitroprusside as well as mesenteric lactate and creatinine phosphokinase release were also determined. The administration of INO-1001 led to a significantly improved recovery of left ventricular systolic function (p < .05) after 60 mins of reperfusion. Coronary and mesenteric blood flow were also significantly higher in the INO-1001 group (p < .05). Although the vasodilatory response to sodium nitroprusside was similar in both groups before and after cardiopulmonary bypass and similar in response to acetylcholine before cardiopulmonary bypass, PARP-inhibited dogs had lower mesenteric vascular resistance after cardiopulmonary bypass (p < .05). Mesenteric lactate and creatinine phosphokinase release was significantly lower in the PARP inhibitor treated group (p < .05). CONCLUSION: PARP inhibition with INO-1001 improves the recovery of myocardial function and prevents mesenteric vascular dysfunction and tissue injury after cardiopulmonary bypass with hypothermic cardiac arrest.
Descriptors: cardiac function, mesenteric function, ultrapotent poly(adenosine 5'-diphosphate-ribose) polymerase (PARP), cardiopulmonary bypass .

Szigeti, Z., K. Simon, J.R. Parratt, and A. Vegh (2004). Effects of delayed preconditioning on myocardial regional contractility during repeated episodes of low-flow ischaemia in anaesthetized dogs: possible role of nitric oxide. Clinical Science (London) 106(2): 201-213. ISSN: 0143-5221.
NAL Call Number: RB37.C43
Abstract: The effect of cardiac pacing on repeated low-flow ischaemia-induced changes in regional myocardial segmental contractility, and the role in these changes of nitric oxide, were investigated in anaesthetized dogs. Dogs were instrumented for cardiac pacing (pacing electrode in the right ventricle). Dogs were paced (four times for 5 min; pacing rate 220 beatscntdotmin-1) 24 h prior to the repeated ischaemic insults. Controls were instrumented, but not paced. After 24 h, the dogs were re-anaesthetized with pentobarbitone and subjected to four 20 min low-flow ischaemia and reperfusion cycles, by constricting the left anterior descending coronary artery (LAD) to achieve an approx. 50% reduction in resting coronary blood flow. In some dogs (both control and paced), NG-nitro-L-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase) was infused into a side-branch of the LAD 10 min prior to the first ischaemia/reperfusion cycle. Regional contractile function was measured by ultrasonic microcrystals in the ischaemic and normal regions of the left ventricular wall supplied from the LAD and left circumflex coronary artery respectively, and expressed as percentage changes in segmental shortening (%SS). In some dogs, myocardial tissue blood flow (coloured microspheres) and lactate production (local coronary venous sampling) were measured; samples were also taken for histological analysis. In control dogs, the regional %SS was progressively reduced within the ischaemic segment during the four repeated occlusions (by 40+-6, 59+-6, 68+-6, 70+-6% during occlusions 1-4 respectively). These reductions were more pronounced, especially during the first two cycles (68+-6, 68+-6, 67+-6, 67+-6%, respectively), when the dogs had been previously subjected to cardiac pacing. In both paced and control dogs, these changes in contractile function were L-NAME-sensitive. Thus, in the presence of L-NAME, changes in regional segmental shortening in control dogs were 37+-8, 40+-8, 37+-8, 42+-11% and in the paced dogs 4+-6, 45+-7, 45+-8, 45+-7% respectively, during the four consecutive occlusions. There were no significant differences in tissue blood flow or in lactate production between the groups, and no structural changes indicative of infarction. These results show that the myocardium rapidly adapts to re-occurring acute ischaemia by reducing contractility within the ischaemic segment and, thereby, metabolic demand. Furthermore, cardiac pacing 24 h prior to these ischaemic challenges induces a similar adaptive response, a form of 'delayed preconditioning'. Since both the acute and delayed adaptation were L-NAME-sensitive, we suggest that this adaptation involves nitric oxide.
Descriptors: cardiovascular system, transport and circulation, histology, histology and cytology techniques, laboratory techniques.

Tabata, T., R.A. Grimm, J. Asada, Z.B. Popovic, H. Yamada, N.L. Greenberg, D.W. Wallick, Y. Zhang, S. Zhuang, K.A. Mowrey, J.D. Thomas, and T.N. Mazgalev (2004). Determinants of lv diastolic function during atrial fibrillation: beat-to-beat analysis in acute dog experiments. American Journal of Physiology 286(1 Part 2): H145-H152. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral (Evti) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/dtmin), and the time constant of LV pressure decay (tau) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with Evti (r=0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r=0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r=0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/dtmin (r=0.95) and tau (r=-0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/dtmin and tau (r=-0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lenthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, atrial fibrillation, heart disease, doppler echocardiography, clinical techniques, diagnostic techniques, cardiac cycle.

Takahara, A., A. Sugiyama, Y. Satoh, Y. Nakamura, T. Konda, and K. Hashimoto (2003). L-plus n-type ca2+ channel blocker cilnidipine reduced arrhythmogenic substrates in the canine sudden cardiac death model with hypertension. American Journal of Hypertension 16(5 Part 2): 130A. ISSN: 0895-7061.
NAL Call Number: RC685.H8
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology, arrhythmia, heart disease, atrio ventricular block, hypertension, vascular disease, sudden cardiac death, holter electrocardiography, laboratory techniques, cardiac output, electrophysiological parameters, hemodynamic parameters, mean blood pressure, monophasic action potential, neurohumoral parameters, ventricular repolarization.

Takahara, A., A. Sugiyama, Y. Satoh, M. Yoneyama, and K. Hashimoto (2003). Cardiovascular effects of y-27632, a selective rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model. European Journal of Pharmacology 460(1): 51-57. ISSN: 0014-2999.
NAL Call Number: QP901.E8
Abstract: Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, is a selective Rho-associated kinase inhibitor, which has been suggested to possess multiple clinical applications based on the in vitro observations. Since information regarding in vivo cardiovascular effects of Y-27632 is still limited, we assessed them using the halothane-anesthetized, closed-chest canine model. Administration of Y-27632 in a dose of 0.01 mg/kg, i.v. significantly decreased total peripheral vascular resistance together with an increase of cardiac output without affecting other cardiovascular parameters. Moreover, additional administration of Y-27632 in a dose of 0.1 mg/kg, i.v. significantly decreased blood pressure and left ventricular end-diastolic pressure, increased the heart rate and cardiac contractility, enhanced atrioventricular conduction and shortened the repolarization process as well as the effective refractory period. These results indicate that Y-27632 exerts a potent arterio-venodilator action with cardiostimulatory effects possibly through the sympathetic reflex in the in vivo canine model.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, arterio venodilator action, blood pressure, cardiac contractility, cardiac output, heart rate, left ventricular end diastolic pressure, monophasic action potential, sympathetic reflex.

Takahashi, M., T. Nakamura, T. Toba, H. Kato, and Y. Shimizu (2003). Cell transplantation of endothelial progenitor cells into lung improves pulmonary hypertension canine model. XXX Congress of the European Society for Artificial Organs (ESAO) on High Tech and Medicine, Aachen, Germany; September 03-06, 2003,Vol. 26(7): 611,
Descriptors: cardiovascular system, transport and circulation, respiratory system, respiration, pulmonary hypertension, vascular disease, therapy, cell transplantation, clinical techniques, therapeutic and prophylactic techniques, neovascularization .

Takehana, K., G.A. Beller, M. Ruiz, F.D. Petruzella, D.D. Watson, and D.K. Glover (2001). Assessment of residual coronary stenoses using 99mtc-n-noet vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction. Journal of Nuclear Medicine 42(9): 1388-1394. ISSN: 0161-5505.
NAL Call Number: RM845.J78
Abstract: Reperfusion is often incomplete after recanalization therapy because of the presence of residual coronary stenoses. Detecting mild to moderate stenoses requires assessing coronary flow reserve with vasodilator stress. 99mTc-(N-ethoxy-N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer and thus may be well suited for assessing coronary flow reserve in the acute phase of reperfusion. Methods: Twelve open-chest dogs underwent 60 min of total left anterior descending artery (LAD) occlusion followed by either full reperfusion (group 1; n = 4) or reperfusion through a residual critical stenosis (group 2; n = 8). 99mTc-N-NOET was given during peak vasodilator stress 165 min after reperfusion, and initial and 60-min delayed images were acquired. Regional blood flow was assessed with radiolabeled microspheres. Results: Infarct size was similar in both groups (9% +- 2% vs. 8% +- 2% of left ventricle). Both initial (0.61 +- 0.02 vs. 0.73 +- 0.01; P < 0.01) and 60-min (0.67 +- 0.02 vs. 0.80 +- 0.01; P < 0.01) defect count ratios (LAD/left circumflex coronary artery (LCx)) differentiated between the 2 groups, reflecting the greater diminution in coronary flow reserve in group 2 dogs (LAD/LCx flow ratios = 0.37 +- 0.04 vs. 0.57 +- 0.09; P < 0.01). Interestingly, coronary flow reserve in the reperfused zone of group 1 was diminished despite the absence of a stenosis. Thus, the difference in 99mTc-N-NOET uptake between the 2 groups was less than expected. Conclusion: In this canine myocardial infarction model with some coronary flow reserve preservation, 99mTc-N-NOET imaging can detect residual coronary stenoses. However, with more prolonged occlusion resulting in more severe endothelial or microvascular dysfunction, it may be difficult to distinguish varying degrees of vessel patency using any coronary flow reserve technique.
Descriptors: cardiovascular system, transport and circulation, pharmaceuticals, pharmacology, radiation biology, subendocardial infarction, heart disease, vascular disease, coronary flow reserve, coronary reperfusion, coronary stenosis, nuclear medicine.

Takehana, K., M. Ruiz, F.D. Petruzella, D.D. Watson, G.A. Beller, and D.K. Glover (2000). Detection of residual coronary stenoses by assessing coronary flow reserve using 99mtc-n-noet vasodilator stress imaging early after coronary reperfusion in a canine model of infarction. Journal of the American College of Cardiology 35(2 suppl. A): 493A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, myocardial infarction, heart disease, vascular disease, coronary flow reserve assessment, coronary reperfusion, residual coronary stenosis detection, vasodilator stress imaging, detection method, meeting abstract.

Tarpey, S.B., D.R. Sawmiller, C. Kelly, W.J. Thompson, and M.I. Townsley (2003). Phosphodiesterase 3 activity is reduced in dog lung following pacing-induced heart failure. American Journal of Physiology 284(5 Part 1): L766-L773. ISSN: 0002-9513.
NAL Call Number: 447.8 Am3
Abstract: We hypothesized that decreases in expression and/or activity of cAMP-specific phosphodiesterases (PDE) contribute to protective adaptations observed in lung after heart failure. In this study, we compared PDE activity in lung parenchyma isolated from control dogs and those paced to heart failure by assaying cyclic nucleotide hydrolysis in fractions of homogenate supernatant eluted from DEAE-Trisacryl columns. Cyclic nucleotide hydrolysis due to PDE3, PDE4, and PDE5 isoforms was predominant in both control and paced groups. The ratio of PDE3 activity to total cAMP PDE activity was decreased in the paced group compared with control (P<0.05), whereas PDE4 or PDE5 activity ratios were not different between the two groups. With the use of RT-PCR, message expression for PDE3A or PDE3B did not differ between the two groups. Cilostamide, a selective PDE3 inhibitor, and forskolin, a nonspecific agonist for adenylyl cyclase, both inhibited thapsigargin-induced increases in endothelial permeability in control lung. We conclude that PDE3 activity, but not mRNA expression, is reduced in lung from dogs paced to heart failure, a change that could contribute to heart failure-induced attenuation of the lung endothelial permeability response to injury.
Descriptors: cardiovascular system, transport and circulation, enzymology, biochemistry and molecular biophysics, respiratory system, respiration, heart failure, heart disease, cardiac pacing, laboratory techniques.

Thibault, B., A. Ducharme, Y.F. Shi, M. Dubuc, P. Guerra, L. Macle, D. Roy, M. Talajic, and J.C. Tardif (2004). In the rapid pacing canine model of heart failure, left ventricular stimulation resynchronizes better the left ventricle compared to biventricular or right ventricular stimulation: an echocardiographic-hemodynamic correlation of systolic and diastolic function. Journal of the American College of Cardiology 43(): (5 Supplement A): 132A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, left ventricular dysfunction, heart disease, mitral regurgitation, severe heart failure, resynchronization therapy, clinical techniques, therapeutic and prophylactic techniques, lvef [left ventricular ejection fraction], pr interval, pulmonary pressure.

Thompson, K., R.T. Thompson, J. Sykes, and G. Wisenberg (2003). Long-term magnetic resonance imaging/spectroscopy study of cariporide in a canine cardiac ischemia/reperfusion model. Journal of Cardiovascular Pharmacology 41(4): 536-543. ISSN: 0160-2446.
Abstract: Using both 31P and 1H cardiac magnetic resonance techniques, it is possible to monitor the functional (ejection fraction (EF)) and biochemical (pH) status of the heart following a reperfused ischemic insult. This study assessed the effects of Na+/H+ exchange inhibition with cariporide in a closed-chest canine ischemia/reperfusion model. Dogs received 1-mg/kg cariporide treatments for 3 days after occlusion, but were monitored for 10 days. Baseline intracellular pH (+-SEM) for the control and treated groups were 7.10 +- 0.03 and 7.14 +- 0.04, respectively, and dropped to 6.25 +- 0.08 and 6.38 +- 0.08 during occlusion. There was a significant increase in pH from occlusion to early reperfusion in the control group (P = 0.03) but, during the same time period, this increase was not seen in the cariporide group. There was a significant (P = 0.01) drug interaction in recovery of EF over the 10-day protocol. Individual time-point analysis revealed significant differences at immediate reperfusion through day 3 (73.9% +- 2.5%, 84.5% +- 3.1%; baseline normalized EF controls and cariporide, respectively). Neither pH nor EF measurements were significantly different between the groups at day 10. Despite early functional and metabolic benefits, infarct size, as measured at day 10, was 13.2% +- 2.2% for the controls and 11.8% +- 2.3% for the cariporide group (NS). Thus there were no long-term cariporide functional or biochemical benefits.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, pharmacology, cardiac ischemia reperfusion injury, heart disease, injury, vascular disease, magnetic resonance imaging, imaging and microscopy techniques, laboratory techniques, magnetic resonance spectroscopy, spectrum analysis techniques, ejection fraction, intracellular ph, long term study, sodium ion proton exchange.

Thomsen, M.B., P.G.A. Volders, M. Stengl, R.L. Spatjens, J.D.M. Beekman, U. Bischoff, M.A. Kall, K. Frederiksen, J. Matz, and M.A. Vos (2003). Electrophysiological safety of sertindole in dogs with normal and remodeled hearts. Journal of Pharmacology and Experimental Therapeutics 307(2): 776-784. ISSN: 0022-3565.
NAL Call Number: 396.8 J82
Abstract: Inhibition of the potassium current IKr and QT prolongation are associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of sertindole, an antipsychotic drug reported to prolong the QT interval in schizophrenic patients. In cell cultures, sertindole seemed to be a selective blocker of IHERG over other ion currents. For IHERG, the IC50 value was 64 +- 7 nM, whereas ISCN5A, ICa,L, ICa,T, IKCNQ1/KCNE1, and IKv4.3 were blocked in the micromolar range. In canine ventricular myocytes, the IC50 value for IKr inhibition by sertindole was 107 +- 21 nM. Action potentials in these cells prolonged in a reverse rate- and concentration-dependent manner at 10 to 300 nM sertindole. In vivo, sertindole was administered to anesthetized dogs at clinically relevant (0.05-0.20 mg/kg) and high doses (1.0-2.0 mg/kg) i.v. At 0.05 to 0.20 mg/kg sertindole (plasma concentrations 30-157 nM), QTc was prolonged by 1 to 5% in normal dogs and by 9 to 20% in dogs with remodeled hearts due to chronic atrioventricular block (CAVB). TdP was not induced at these doses in normal dogs or in CAVB dogs with reproducible induction of TdP by dofetilide in previous experiments. At 1.0 to 2.0 mg/kg sertindole (plasma concentrations 0.5-3.1 muM), QTc prolonged by 6 to 11% in normal dogs and by 22% in dofetilide-sensitive CAVB dogs. TdP occurred in three of five animals in the latter group. Thus, at high i.v. doses sertindole can pose a serious proarrhythmic risk when electrical remodeling of the ventricles is present. At clinically relevant doses, however, sertindole does not cause TdP in anesthetized dogs with normal or remodeled hearts.
Descriptors: behavior, cardiovascular system, transport and circulation, pharmacology, schizophrenia, behavioral and mental disorders, drug therapy, sudden cardiac death, heart disease, toxicity, drug induced, prevention and control, torsades de pointes arrhythmias, drug induced, prevention and control, electrophysiology, clinical techniques, i ca,l current, i ca,t current, i herg current, i kcnq1, kcne1 current, i kv4.3 current, i scn5a current, qt prolongation, chronic atrioventricular block.

Thornhill, R.E., F.S. Prato, G. Wisenberg, G.R. Moran, and J. Sykes (2004). Determining the extent to which delayed-enhancement images reflect the partition-coefficient of gd-dtpa in canine studies of reperfused and unreperfused myocardial infarction. Magnetic Resonance in Medicine 52(5): 1069-1079. ISSN: 0740-3194.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, myocardial infarction, heart disease, vascular disease, prevention and control, therapy, bolus, drug delivery device, delayed enhancement imaging, imaging and microscopy techniques, laboratory techniques, infusion therapy, clinical techniques, therapeutic and prophylactic techniques, magnetic resonance imaging, clinical techniques, diagnostic techniques, image delay time, necrosis, partition coefficient, time postinfarction.

Tonduangu, D., L. Hittinger, B. Ghaleh, P. Le Corvoisier, L. Sambin, S. Champagne, T. Badoual, F. Vincent, A. Berdeaux, B. Crozatier, and J.B. Su (2004). Chronic infusion of bradykinin delays the progression of heart failure and preserves vascular endothelium-mediated vasodilation in conscious dogs. Circulation 109(1): 114-119. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background-This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure. Methods and Results-Sixteen instrumented dogs were randomized to receive through the left atria either vehicle or bradykinin (1 mug/min) during ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV) parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3 mug/kg) and nitroglycerin (1 to 10 mug/kg) were examined in the control and after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral, carotid, and renal arteries was determined by Western blot analysis. After 3 weeks of pacing, changes in LV diastolic and systolic parameters were significantly lower in bradykinin-treated than vehicle-treated dogs (LV end-diastolic pressure, +10+-3 versus +19+-2 mm Hg; time constant of LV isovolumic relaxation, +11+-2 versus +17+-1 ms; LV wall thickening, -33+-18% versus -75+-9%; and cardiac output, -16+-6% versus -32+-6%; all P<0.05). Compared with vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of the diastolic LV pressure-diameter relation and a reduced diastolic LV wall stress. Similar trends were observed after 5 weeks. The vasodilator response to nitroglycerin was preserved in both groups. The response to acetylcholine was blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular endothelial NOS expression decreased in vehicle-treated but was preserved in bradykinin-treated dogs. Conclusions-In conscious dogs, chronic bradykinin infusion delays the heart failure progression by preserving LV diastolic and systolic functions and by preserving vascular endothelial function.
Descriptors: cardiovascular system, transport and circulation, pharmacology, heart failure, heart disease, hemodynamics, myocardial functions, vascular endothelium mediated vasodilation.

Trumble, D.R. and J.A. Magovern (2004). Comparison of dog and pig models for testing substernal cardiac compression devices. ASAIO Journal (American Society for Artificial Internal Organs) 50(3): 188-92. ISSN: 1058-2916.
Abstract: Subtle anatomic differences between species can be a critical consideration when determining whether a given animal model is appropriate for surgical research purposes, especially when testing biomechanical implants. This study compares the effectiveness of two common animal models (dogs and pigs) in testing a balloon based cardiac compression device designed for substernal placement. Pigs were used in acute studies using an infarction model of heart failure, whereas dogs were used in chronic experiments in which heart failure was induced via rapid pacing. Systolic cardiac compression was accomplished in both species using identical balloons inflated between the sternum and right ventricle with every heartbeat. Results showed the device to be much more effective in pigs, where cardiac stroke volumes returned to normal with balloon assistance (14.7 +/- 1.9 to 37.8 +/- 9.2 mL, p < 0.005). Stroke volumes in dogs, however, remained essentially unaltered by balloon activation (28.1 +/- 14.1 to 29.6 +/- 14.7 mL, p = NS). Retrospective comparisons showed pig models to be a much closer approximation to the human anatomy because of a more similar thoracic cavity shape and heart orientation. These findings suggest that certain large animal models should not be used in research in which chest wall shape or cardiac orientation within the thoracic cavity may influence outcomes.
Descriptors: animal model, species differences, dog versus pig, antomical differences, surgical research, biomechanical implants, infarction models, heart failure.

Tse, L.W., B.T. Bui, S. Lerouge, I. Salazkin, E. Therasse, A. Benko, H. Heon, V.L. Oliva, and G. Soulez (2007). In vivo antegrade fenestration of abdominal aortic stent-grafts. Journal of Endovascular Therapy an Official Journal of the International Society of Endovascular Specialists 14(2): 158-67. ISSN: 1526-6028.
Abstract: PURPOSE: To examine in a canine model the feasibility of antegrade fenestration of abdominal aortic stent-grafts to preserve the patency of the renal arteries. METHODS: Two large dogs underwent antegrade fenestration of stent-grafts in the perirenal aorta. Before fenestration, bare stents were inserted in both renal arteries as fluoroscopic landmarks. A 12-mm iliac extension served as the canine aortic endograft. The first procedure was done under ultrasound and fluoroscopic guidance, using an intravascular ultrasound (IVUS) probe inserted in the vena cava and a Pioneer IVUS catheter. The second was performed exclusively under fluoroscopic guidance with a Brockenbrough needle. Angiograms and duplex ultrasound were planned for 1 month, after which the dogs would be sacrificed for autopsy. The explanted endograft was subjected to biomaterials analysis, with a focus on fabric tear. RESULTS: Perforation of the aortic graft and catheterization of the renal arteries with a floppy guidewire were possible in both animals. In dog 1, aortic graft dilation and subsequent fenestration were not possible, and the experiment was terminated. However, the procedure was successful in both renal arteries of dog 2. At 1-month follow-up in this dog, both renal arteries were patent. Stent fractures were observed bilaterally. There was no extension of the damage to the fabric beyond the area of fenestration. CONCLUSION: In vivo antegrade fenestration of aortic endografts is technically feasible. However, improvements in technique, instrumentation, and materials are required to make it a reliable and reproducible way of allowing stent-graft vascularization of aortic side branches.
Descriptors: aorta, abdominal surgery, blood vessel prosthesis, blood vessel prosthesis implantation, renal artery surgery, stents, aorta, abdominal radiography, aorta, abdominal ultrasonography, aortography, dogs, feasibility studies, models, animal, prosthesis design, radiography, interventional, renal artery radiography, renal artery ultrasonography, time factors, ultrasonography, interventional, vascular patency.

Tsutsui, J.M., P.M. Dourado, A.C.P. Chagas, W.J. Mathias, J.L. Andrade, and P.L. Da Luz (2003). Evaluation of infarcted and risk areas by real-time myocardial contrast echocardiography in an open-chest canine model. FASEB Journal 17(4-5): Abstract No. 342.17. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, methods and techniques, ischemia, vascular disease, myocardial infarction, heart disease, real time myocardial contrast echocardiography, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, infarcted, risk areas, evaluation method, methodology, open chest canine model, uses, perfusional myocardial defects, evaluation, wall motion defects, evaluation.

Tucci, P.J.F., O.J. Sant'ana, R.J. Nogueira, N. Murad, A.C. Lopes, A. Sanudo, and C.A. Peres (2003). Stunning and myocardial contractile autoregulation studied on the isolated isovolumic blood-perfused dog heart. Acta Physiologica Scandinavica 179(3): 263-271. ISSN: 0001-6772.
NAL Call Number: QP1.A2
Abstract: Aim: To study, for the first time, the effects of stunning on homeometric and heterometric autoregulation. Methods and results: Ischaemia (15 min)/reperfusion (30 min) was induced in the isovolumic blood-perfused dog heart preparation. Heart rate elevations (n = 9) from 60 to 200 beats min-1, in steps of 20 beats min-1, promoted the same inotropic stimulation in control (C) and stunning (S), indicating that ischaemia/reperfusion does not affect the changes in calcium kinetics elicited by the Bowditch effect. Sudden ventricular dilation (VD) (n = 10) evoked an instantaneous increase in developed pressure (DELTA1DP) followed by a continuous slow performance increase (DELTA2DP) in C and S. DELTA1DP (C:35 +- 2.2 mmHg; S:27 +- 2.1 mmHg; P = 0.002) and DELTA2DP (C:20 +- 1.6 mmHg; S:14 +- 1.3 mmHg; P = 0.002) decreased proportionally, while DELTA2DELTADP (C:0.57 +- 0.13; S:0.58 +- 0.14) and slow response time course (T/2) were unchanged (C:55 +- 6.6 s; S:57 +- 7.7 s) after ischaemia/reperfusion. The reduction of DELTA1DP can be understood as a decline of the myofilaments calcium responsiveness, the main pathophysiological effect of stunning. The reason for the weakening of DELTA2DP, due to intracellular calcium gain, was not determined but it was supposed that its complete manifestation could be restricted by cyclic adenosine monophosphate (cAMP) myocardial content reduction. As reported by others, DELTA2DP depends on myocardial cAMP, and it has been shown that myocardial cAMP is decreased after ischaemia/reperfusion. Conclusions: Contractile depression due to stunning has no effect on the inotropic stimulation generated by the Bowditch phenomenon. Immediate and time-dependent enhancements of contraction evoked by sudden VD are proportionally reduced and the slow response time course is unaffected in the stunned myocardium.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, methods and techniques, ischemia,vascular disease, myocardial stunning, heart disease, vascular disease, heart rate.

van Opstal, J.M., P.G. Volders, M. Stengl, E. Martel, U. Gerlach, R.L. Spatjens, J.D. Beekman, K.R. Sipido, and M.A. Vos (2003). Iks contributes importantly to ventricular repolarization in conscious dogs. Journal of the American College of Cardiology 41(6 Supplement A): 112A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation.

Vanderheide, R.S. (2000). Overexpression of stress proteins protects cultured adult canine ventricular myocytes from simulated ischemia/reperfusion injury. Circulation 102(18 Supplement): II.272. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, adenovirus infection, viral disease, cardiac heat shock protein expression, myocardial ischemic injury, heart disease, development, mediation, cell death, meeting abstract.

Verdonck, F., P.G.A. Volders, M.A. Vos, and K.R. Sipido (2003). Increased na+ concentration and altered na/k pump activity in hypertrophied canine ventricular cells. Cardiovascular Research 57(4): 1035-1043. ISSN: 0008-6363.
NAL Call Number: QM178.A1C38
Abstract: Objective: To investigate whether hypertrophy in the dog with chronic atrioventricular block (CAVB) alters (Na+)i and Na/K-pump function of ventricular myocytes. Methods: We measured the (Na+)i dependence of the Na/K pump current, Ip. This relation was used as a calibration curve for (Na+)i based on Ip. We measured Ip at the time of access and extrapolated (Na+) at the pump sites, i.e. subsarcolemmal (Na+), (Na+)subs, from the calibration curve. Results: The extrapolated (Na+)subs was significantly higher in CAVB (7.9 vs. 3.2 mM in control). The (Na+)i dependence of Ip in CAVB myocytes was shifted to the right (range of (Na+)i: 0-20 mM). In resting cells, the Ip, i.e. steady state Na+ efflux, which matches Na+ influx, was higher in CAVB (0.25+-0.02 vs. 0.47+-0.06 pA/pF, P<0.05). Maximal Ip density was not different, and DHO sensitivity was not altered. Conclusions: Hypertrophy in CAVB cells is associated with increased (Na+)subs. This results from an increase in Na+ influx, and a decreased sensitivity of Ip for Na+ in the range of (Na+)i studied. There is no evidence for a decrease in total pump capacity or for a functional Na/K-ATPase isoform shift. The rise in Na+ contributes to the contractile adaptation and preservation of sarcoplasmic reticulum Ca2+ content at the low heart rates of the dog with CAVB.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, cell biology, metabolism, cardiac hypertrophy, heart disease, chronic atrioventricular block.

Veres, G., T. Radovits, H. Schultz, L.N. Lin, J. Hutter, E. Weigang, Z. Szabolcs, and G. Szabo (2007). Effect of recombinant aprotinin on postoperative blood loss and coronary vascular function in a canine model of cardiopulmonary bypass. European Journal of Cardio Thoracic Surgery Official Journal of the European Association for Cardio Thoracic Surgery 32(2): 340-5. ISSN: 1010-7940.
NAL Call Number: RD598
Abstract: OBJECTIVE: Aprotinin is a widely used serine protease inhibitor during cardiopulmonary bypass to reduce blood loss and preserve platelet function. However, the bovine-derived aprotinin can induce hypersensitivity reaction with fatal complications. Furthermore, vascular effects of aprotinin are not completely elucidated. The current study is designed to investigate the effects of recently developed recombinant aprotinin on blood loss and coronary vascular function in a clinically relevant canine model of cardiopulmonary bypass without aortic cross-clamping and cardioplegia. METHODS: Twenty-four dogs underwent cardiopulmonary bypass without aortic cross-clamping and cardioplegia. Dogs were divided into three groups in a blinded fashion: control animals (n=8) received placebo, aprotinin treatment groups received bovine (n=8) or recombinant aprotinin (n=8) according to the Hammersmith method. The doses of bovine and recombinant aprotinin were the same. Coagulation parameters and blood loss were measured regularly at different time points. Endothelium-dependent and -independent vasorelaxation were investigated in isolated left anterior descendent coronary arterial rings by using acetylcholine and bradykinin or sodium nitroprusside and adenosine, respectively. RESULTS: Postoperative blood loss was significantly reduced in the aprotinin-treated groups in comparison to control and there was no significant difference between the two aprotinin-treated groups. Endothelium-dependent relaxation of coronary arteries to acetylcholine and bradykinin was unaffected in the aprotinin treatment groups. Both types of aprotinin significantly increased vasorelaxation to adenosine when compared with controls, but did not affect that to sodium nitroprusside. CONCLUSIONS: The effectiveness of recombinant aprotinin on blood loss was equivalent to bovine-derived aprotinin. Neither types of aprotinin impaired endothelium-dependent relaxation in a canine model of cardiopulmonary bypass.
Descriptors: aprotinin administration and dosage, cardiopulmonary bypass methods, coronary vessels drug effects, postoperative hemorrhage prevention and control, serine proteinase inhibitors administration and dosage, 15 hydroxy 11 alpha,9 alpha epoxymethanoprosta 5,13 dienoic acid pharmacology, acetylcholine pharmacology, blood coagulation drug effects, blood coagulation physiology, bradykinin pharmacology, cattle, coronary vessels physiopathology, dogs, drug administration schedule, endothelium, vascular drug effects, endothelium, vascular physiopathology, models, animal, myocardial contraction drug effects, myocardial contraction physiology, nitroprusside pharmacology, recombinant proteins administration and dosage, vasoconstrictor agents pharmacology, vasodilator agents pharmacology.

Verheule, S., E. Wilson, T.I. Everett, S. Shanbhag, C. Golden, and J. Olgin (2003). Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation. Circulation 107(20): 2615-2622. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background-Clinically, chronic atrial dilatation is associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism is not clear. We have investigated atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation (MR). Methods and Results-Thirteen control and 19 MR dogs (1 month after partial mitral valve avulsion) were studied. Dogs in the MR group were monitored using echocardiography and Holter recording. In open-chest follow-up experiments, electrode arrays were placed on the atria to investigate conduction patterns, effective refractory periods, and inducibility of AF. Alterations in tissue structure and ultrastructure were assessed in atrial tissue samples. At follow-up, left atrial length in MR dogs was 4.09+-0.45 cm, compared with 3.25+-0.28 at baseline (P<0.01), corresponding to a volume of 205+-61% of baseline. At follow-up, no differences in atrial conduction pattern and conduction velocities were noted between control and MR dogs. Effective refractory periods were increased homogeneously throughout the left and right atrium. Sustained AF (>1 hour) was inducible in 10 of 19 MR dogs and none of 13 control dogs (P<0.01). In the dilated MR left atrium, areas of increased interstitial fibrosis and chronic inflammation were accompanied by increased glycogen ultrastructurally. Conclusions-Chronic atrial dilatation in the absence of overt heart failure leads to an increased vulnerability to AF that is not based on a decrease in wavelength.
Descriptors: cardiovascular system, transport and circulation, atrial fibrillation, heart disease, chronic atrial dilatation, chronic inflammation, immune system disease, heart failure, interstitial fibrosis, disease miscellaneous, mitral regurgitation, holter recording, laboratory techniques, echocardiography, electrode array, laboratory equipment, partial mitral valve avulsion, experimental surgical techniques.

Vincent, I.C. and R.A. Leahy (1997). Real-time non-invasive measurement of heart rate in working dogs: a technique with potential applications in the objective assessment of welfare problems. Veterinary Journal 153(2): 179-183. ISSN: 1090-0233.
NAL Call Number: SF601.V484
Abstract: The Polar Sport Tester (Polar Electro OY) is a telemetric heart rate monitor designed for use in humans. Its usefulness as a monitor during training of guide dogs is assessed in this paper. Heart rates from six representative dogs at a similar stage of early training were recorded at 5-s intervals during a 15-20 min work session. The dogs were F1 Labrador Retriever times Golden Retrievers. They were chosen if their behaviour could be clearly categorized by their experienced trainers as either 'calm/non-stress prone' (Type A) or 'excitable/stress prone' (Type B) during work. Verbal recordings were made of environmental cues and behavioural responses in each dog. Variability in heart rate was significantly related to a subject's described temperament.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, veterinary medicine, medical sciences, breed f1 labrador x golden retriever, cardiovascular system, heart rate monitor, heart rate real time non invasive measurement, methodology, polar sport tester, potential applications, technique, temperament relation, verbal recordings, veterinary medicine, welfare problems, working dogs.

Wang, L., D.M. Zhu, X. Su, C.X. Bai, L.B. Ware, and M.A. Matthay (2004). Acute cardiopulmonary effects of a dual-endothelin receptor antagonist on oleic acid-induced pulmonary arterial hypertension in dogs. Experimental Lung Research 30(1): 31-42. ISSN: 0190-2148.
Abstract: The objective of this study was to evaluate the cardiopulmonary effects of a dual-endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve Pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n=6) received saline treatment, whereas the treatment group (n=6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous (IV)+1 mg/kg/h IV infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all-dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23+-2 mm Hg to 15+-2 mm Hg; P<.01) and a 22% decrease in PVR (from 860+-105 dyncntdotscntdotcm-5 to 670+-96 dyncntdotscntdotcm-5; P<.01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual-ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual-ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.
Descriptors: cardiovascular system, transport and circulation, pharmacology, respiratory system, respiration, veterinary medicine, medical sciences, acute lung injury, injury, respiratory system disease, pulmonary arterial hypertension, respiratory system disease, vascular disease, chemically induced, vascular disease, mean pulmonary arterial pressure [mpap], systemic vascular resistance.

Wang, M. and M.A. Lung (2003). Adrenergic mechanisms in canine nasal venous systems. British Journal of Pharmacology 138(1): 145-155. ISSN: 0007-1188.
NAL Call Number: 396.8 B77
Abstract: 1 We investigated the adrenergic mechanisms of the two venous systems that drain the nasal mucosa, thereby their exact role in eliciting nasal decongestion. The action of endogenously released noradrenaline and exogenous adrenergic agonists on different segments of the nasal venous systems, i.e. collecting (LCV, SCV) and outflow (SPV) veins of posterior venous system, collecting (ACV) and outflow (DNV) veins of anterior venous system and venous sinusoids of the septal mucosa (SM), were studied. In vitro isometric tension of the vascular segments was measured. 2 Transmural nerve stimulation (TNS) produced constriction in ACV, DNV and SM, primary constriction followed by secondary dilatation in LCV and SCV and dilatation in SPV. Tetrodotoxin (10-6 M) abolished all responses. Phentolamine (10-6 M), prazosin (10-6 M) and rauwolscine (10-7 M) inhibited the constriction in all venous vessels. Propranolol (10-6 M), atenolol (10-6 M) and ICI 118,551 (10-6 M) inhibited the relaxation in SPV but not in LCV and SCV. Phenylephrine and clonidine constricted whereas dobutamine and terbutaline relaxed all venous vessels dose-dependently. 3 These results indicate alpha1-, alpha2-, beta1- and beta2-adrenoceptors are present in both venous systems. TNS causes constriction of anterior venous system, venous sinusoids and posterior collecting veins primarily via postjunctional alpha2-adrenoceptors but relaxation of posterior outflow vein equally via postjunctional beta1- and beta2-adrenoceptors. The combined action of the two adrenergic mechanisms can reduce nasal airway resistance in vivo by decreasing vascular capacitance and enhancing venous drainage via the posterior venous system.
Descriptors: cardiovascular system, transport and circulation, pharmacology, respiratory system, respiration, nasal decongestion, respiratory system disease, transmural nerve stimulation, laboratory techniques, adrenergic mechanisms, isometric tension, nasal airway resistance, vascular capacitance, vasoconstriction, vasodilation, venous drainage.

Wang Qiu Jing , Lu Weng Wei , Lu Hang , Liu Fen , Yang Shi Jie , Hua Yu Qiang , and Ji Shu Xia (2003). Protective effect of qi dong yi xin on acute myocardial infarction in dogs. Zhongguo Zhongyao Zazhi 28(5): 449-452. ISSN: 1001-5302.
Abstract: Objective: To observe the protective effects on acute myocardial infarction of QDYX in dog. Method: The corconary ciculation and cardial oxygen metabolism, the degree and range of myocardial ischemia, myocardial infarct size, and the changes of the enzymes in serum were determined by using the acute myocardial infarction model of ligation of LAD in the anaesthetized open-chest dogs. Result: The coronary resistance and cardial oxygen consumption were decreased and the myocardial blood flow was increased in dogs treated with QDYX of 1.0, 2.0 mgcntdotkg-1. The degree and range of myocardial ischemia, myocardial infarct size and the activity of serum CK, LDH were decreased in acute myocardial infarcion dogs treated with QDYX of 1.0, 2.0 mgcntdotkg-1. Conclusion: QDYX can decrease cardial oxygen consumption in dogs, thus having protective effect on myocardial ischemia.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacognosy, pharmacology, acute myocardial infarction, heart disease, vascular disease, diagnosis, prevention and control, therapy, coronary circulation.
Language of Text: Chinese.

Wang, T.M., C.E. Chiang, J.R. Sheu, C.H. Tsou, H.M. Chang, and H.N. Luk (2003). Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves: a contradictory report. International Journal of Cardiology 89(2-3): 187-195. ISSN: 0167-5273.
Abstract: Pulmonary veins may serve as source of ectopic focus (or foci) in initiating atrial tachyarrhythmias in human beings. However, the animal model for such focal atrial fibrillation is still lacking and cellular mechanism for arrhythmias remains to be studied. Recently, a series of reports of cellular electrophysiological characterization of pulmonary vein sleeves demonstrated an extremely high incidence of automaticity (varied from 40 to 76%) and triggered activity (from 0 to 44%) in normal healthy control dogs and rabbits. The present study was therefore designed to re-investigate the cellular electrophysiological properties of canine pulmonary veins. Intracellular action potentials were characterized in pulmonary vein sleeves in 50 normal healthy dogs. Conventional glass microelectrode recording technique was used. Experiments were focused on the incidence of automaticity and triggered activity in pulmonary vein sleeve tissues. Surprisingly, our results showed that all pulmonary vein sleeves tissues in these dogs displayed fast-response action potentials under the well-controlled experimental condition (100%, n=50). No spontaneous pacemaking activities, early or delayed afterdepolarisations were observed (0%, n=50). No high-frequency spikes or irregular rhythm could be recorded in all experiments (0%, n=50). Both the frequency response and membrane responsiveness of the pulmonary vein action potentials were characterized. No electrophysiological inhomogeneity between the distal and the proximal part of the sleeves was observed. In conclusion, canine pulmonary vein sleeves do not display arrhythmogenic activities under normal physiological conditions. The possible explanations for the controversy in pulmonary veins electrophysiology were discussed.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, arrhythmia, heart disease, atrial fibrillation.

Weber, T.P., M.A.G. Hartlage, N. Rolf, M. Booke, E. Berendes, H. Van Aken, and A. Meissner (2003). Short-term administration of ethanol does not affect functional recovery from myocardial stunning in awake dogs. Anesthesia and Analgesia 96(3): 665-672. ISSN: 0003-2999.
Abstract: Chronic ingestion of small doses of ethanol protects the myocardium from ischemic damage. It was demonstrated that short-term administration of ethanol (SAE) enhances the recovery of stunned myocardium in acutely instrumented, anesthetized dogs. It is unclear whether this beneficial effect of SAE also occurs in awake dogs. Therefore, we investigated the effects of SAE on regional myocardial stunning in awake dogs. Thirty-six dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, left systolic ventricular contactility (dP/dtmax) and diastolic ventricular function (dP/dtmin), and regional myocardial wall-thickening fraction (WTF). Occluders around the left anterior descending (LAD) artery allowed the induction of reversible ischemia in the LAD-perfused myocardium. The dogs were assigned to one of three groups that differed in the dose of ethanol administered in the ethanol experiment (I, 0.125 g/kg (n = 12); II, 0.25 g/kg (n = 12); III, 0.5 g/kg (n = 12)). In each group, the dogs underwent two ischemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion after the application of ethanol IV over 30 min (ethanol group) and without ethanol (control). WTF and hemodynamic variables were measured at baseline and at predetermined time points until complete recovery of myocardial stunning occurred. LAD-ischemia led to a significant decrease of LAD-WTF in all groups. There was no difference in WTF and hemodynamic variables with or without SAE during reperfusion. We conclude that SAE (0.125 g/kg, 0.25 g/kg, and 0.5 g/kg) does not significantly affect myocardial stunning in conscious dogs.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, methods and techniques, myocardial stunning, heart disease, vascular disease.

Weinberg, G., R. Ripper, D.L. Feinstein, and W. Hoffman (2003). Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Regional Anesthesia and Pain Medicine 28(3): 198-202. ISSN: 1098-7339.
Abstract: Background and Objectives: We previously demonstrated in rats that intravenous infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to determine if this method is similarly effective in a non-rodent model using a larger animal. Methods: Bupivacaine, 10 mg/kg, was administered intravenously over 10 seconds to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 minutes of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 minutes. Electrocardiogram (EKG), arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. Results: Survival after 10 minutes of unsuccessful cardiac massage was successful for all lipid-treated dogs (n=6), but with no survivors in the saline controls (n=6) (P<.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. Conclusions: We found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, toxicology, resuscitation, clinical techniques, therapeutic and prophylactic techniques.

Werner, P., M.G. Raducha, U. Prociuk, E.O. Ostrander, R.S. Spielman, E.F. Kirkness, D.F. Patterson, and P.S. Henthorn (2003). Genome-wide scan for conotruncal heart defect loci in a canine model. American Journal of Human Genetics 73(5): 517. ISSN: 0002-9297.
NAL Call Number: QH431.A1A54
Descriptors: cardiovascular system, transport and circulation, molecular genetics, biochemistry and molecular biophysics, conal ventricular septal defect, congenital disease, heart disease, genetics, conotruncal heart defect, conus septum defect, isolated congenital heart defects, persistent truncus arteriosus, tetralogy of Fallot, genehunter, computer software, genehunter twolocus analysis, genetic techniques, laboratory techniques, mathematical and computer techniques, lod score, genome wide scan, two point linkage analysis, genetic techniques, autosomal recessive inheritance model, non mendelian inheritance patterns.

Willigers, H.M., F.W. Prinzen, P.M. Roekaerts, S. De Lange, and M.E. Durieux (2003). Dexmedetomidine decreases perioperative myocardial lactate release in dogs. Anesthesia and Analgesia 96(3): 657-664. ISSN: 0003-2999.
Abstract: The sympatholytic effect of the alpha2-adrenergic agonist dexmedetomidine may decrease emergence-related myocardial ischemic load in patients. However, a direct measure of myocardial ischemia, such as myocardial lactate release, is difficult to obtain in patients. Therefore, we studied mongrel dogs and measured myocardial lactate release, myocardial oxygen supply, hemodynamic variables, and neurohumoral indices of the stress response. After the induction of a standardized degree of borderline myocardial ischemia, either dexmedetomidine (dexmed group, n = 9) or normal saline (control group, n = 9) was infused. Measurements were repeated at the end of the anesthetic period and every 10 min during the 90-min emergence period. In the dexmed group, the cumulative emergence-related lactate release was 46% less than in the control group (95% confidence interval, 20%-80%; P = 0.02). Simultaneously, dexmedetomidine increased the endo-/epicardial blood flow ratio by 35% (control group, 0.4 +- 0.1; dexmed group, 0.6 +- 0.1; P = 0.03). These antiischemic effects of dexmedetomidine were accompanied by reduced plasma concentrations of norepinephrine (126 versus 577 pg/mL) and epinephrine (158 versus 1909 pg/mL) and a slower heart rate (123 +- 6 versus 160 +- 10 bpm, dexmed versus control). The antiischemic effect of dexmedetomidine started before emergence, as evidenced by a decreased prevalence of myocardial lactate release at that time (zero of eight dogs in the dexmed group and four of seven dogs in the control group had lactate release before emergence; P = 0.03).
Descriptors: cardiovascular system, transport and circulation, metabolism, pharmacology, myocardial ischemia, heart disease, vascular disease.

Wu, M.H.D., Y. Kouchi, Y. Onuki, Q. Shi, H. Yoshida, S. Kaplan, R.F. Viggers, R. Ghali, and L.R. Sauvage (1995). Effect of differential shear stress on platelet aggregation, surface thrombosis, and endothelialization of bilateral carotid-femoral grafts in the dog. Journal of Vascular Surgery 22(4): 382-392. ISSN: 0741-5214.
Abstract: Purpose: The purpose of this study was to determine the effects of increased shear stress on the aggregability of platelets as they traverse a long, small-caliber (6 min) Dacron graft in the dog and on the surface thrombosis and endothelialization of such a graft. Methods: Each of nine dogs received bilateral carotid-femoral artery grafts, approximately 75 cm long, for 3 months; one graft of each pair had a distal femoral arteriovenous fistula to produce a higher shear rate than the contralateral graft. Platelet aggregation scores were determined on blood withdrawn from the external jugular vein and eta-m the proximal and distal ends of the grafts in each animal. Graft flow rates, which were used in the computation of shear stress, and luminal pressure gradients through grafts were measured during surgery and specimen retrieval. Specimens were studied with light microscopy after hematoxylin and eosin and immunocytochemical staining and by scanning electron and transmission electron microscopy to evaluate the nature, composition, and thickness of the flow surface lining, as well as the transmural healing. Results: Two high-shear stress and two low-shear stress grafts occluded unilaterally; five dogs had bilaterally patent grafts, allowing comparative analyses. AR subjects had low platelet aggregability with aspirin. Platelet aggregation scores taken from proximal and distal ends of the grafts were not significantly different. The high-shear stress grafts had significantly more endothelial-like cell coverage (p lt 0.0371) than the low-shear stress grafts, less flow-surface thrombus (p lt 0.0056), and a thinner surface lining (p lt 0.0029), on both the neointima and pseudointima. Conclusions: In subjects with low platelet aggregation scores, long Dacron grafts do not elevate platelet aggregability of blood flowing through them. High-shear stress grafts have less flow surface thrombus, more endothelialization, and a thinner surface lining than do low-shear stress grafts.
Descriptors: blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, cell biology, methods and techniques, morphology, physiology, axillofemoral bypass, dacron graft, graft patency, intimal hyperplasia, surgical method.

Wu, X., C.F. Wang, J. Sheng, and J. Zhu (2004). [Changes in tissue plasminogen activator and plasminogen activator inhibitor during administration of nitroglycerine into internal thoracic artery in dogs with acute myocardial ischemia]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue [Chinese Critical Care Medicine] 16(9): 527-9. ISSN: 1003-0603.
Abstract: OBJECTIVE: To study the changes in tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in a model of acute myocardial infarction reproduced in the dog with administration of nitroglycerin into internal thoracic artery under pressure. METHODS: Sixty healthy cross-breed dogs were randomly divided into experimental and control group with 30 dogs in each group. The animal model of acute myocardial ischemia was reproduced by ligating the left anterior descending coronary artery. Internal thoracic artery in the experimental group was ligated, and a tube was introduced into the proximal end. Nitroglycerine was infused under pressure into the internal thoracic artery in experimental group. The drug was given intravenously in control group. t-PA and PAI were measured before anterior coronary artery ligation and at 0.5, 2 and 6 hours after coronary artery ligation. RESULTS: The t-PA levels in two groups were increased at 0.5 hour after coronary artery ligation, and gradually declined in control group, while no obvious change was found in experimental group. There was significant difference between experimental group and control group at 6 hours after coronary artery ligation(P<0.05). PAI levels were increased after coronary artery ligation, peaking at 6 and 2 hours after coronary artery ligation in both groups. Significant difference in PAI level was observed between two groups at 6 hours after coronary artery ligation(P<0.05). CONCLUSION: Introduction of nitroglycerine through internal thoracic artery under pressure is effective to accelerate release of t-PA from the endothelium while inhibit secretion of PAI, therefore it is useful to modulate the balance of fibrinolysis.
Descriptors: animal model, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), myocardial infarction model, nitroglycerin.
Language of Text: Chinese.

Xiao, L., D. Chartier, W. Han, Z. Wang, and S. Nattel (2003). Gender-based transmural differences in canine cardiac repolarization. Journal of the American College of Cardiology 41(6 Supplement A): 112A. ISSN: 0735-1097.
NAL Call Number: RC681.A1
Descriptors: cardiovascular system, transport and circulation, cardiac repolarization, gender based transmural differences.

Xing, D., A.L. Kjolbye, M.S. Nielsen, J.S. Petersen, K.W. Harlow, N.H. Holstein Rathlou, and J.B. Martins (2003). Zp123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. Journal of Cardiovascular Electrophysiology 14(5): 510-520. ISSN: 1045-3873.
Abstract: ZP123 Prevents Ventricular Tachycardia. Introduction: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. Methods and Results: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +- 0.2 nM: 6/12 vs 0/12; 7.7 +- 0.6 nM: 7/13 vs 1/12; and 69.2 +- 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. Conclusion: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, coronary artery occlusion, heart disease, vascular disease, prevention and control, myocardial ischemia, reentrant ventricular tachycardia, gap junctional conductance.

Xiong, W., F.G. Akar, A.A. Armoundas, I.A. Hobai, B. O'rourke, and G.F. Tomaselli (2004). Na/ca exchange stoichiometry in control and failing canine ventricle. Biophysical Journal 86(1): 551A. ISSN: 0006-3495.
NAL Call Number: 442.8 B5238
Abstract: Na/Ca exchange (NCX) is an essential modulator of Ca homeostasis and contractile function in the heart. The NCX stoichiometry is of considerable interest, but little is known about whether the stoichiometry is altered in heart failure. We investigated the NCX stoichiometry in myocytes isolated from the left ventricular mid-wall of pacing-tachycardia induced failing hearts and control hearts. NCX current was measured in patch-clamped myocytes perfused with solutions of varying extracellular Na or Ca concentrations over a range of holding potentials under conditions that blocked all other known transmembrane Na+ and Ca2+ flux. Analysis of the relationship between the reversal potential and extracellular (Na+) or (Ca2+) in normal cells yielded coupling ratios of 1.90+-0.02 Na+ per net charge (corresponding to 4.22 Na+: 1 Ca2+) and 0.52+-0.01 Ca2+ per net charge (3.92 Na+: 1 Ca2+), consistent with a stoichiometry of 4 Na+ to 1 Ca2+ per transport cycle. Neither a reduction in intracellular (Na+) from 20 to 10 mM nor a change of the holding potential from 0 to -60 mV altered the stoichiometry of NCX. The coupling ratios were 1.87+-0.04 Na+ per net charge (4.29 Na+: 1 Ca2+) and 0.50+-0.03 Ca2+ per net charge (4.00 Na+: 1 Ca2+) in myocytes from failing ventricles. However, when intracellular (Na+) was reduced to 5 mM, the NCX stoichiometry changed to 3.06 Na+: 1 Ca2+ and 3.15 Na+: 1 Ca2+ in normal and failing cells, respectively. We conclude that the stoichiometry of NCX varies from 3:1 at lower intracellular (Na+) to 4:1 at higher intracellular (Na+). The stoichiometries do not differ in patch-clamped ventricular myocytes from control and failing hearts. Nevertheless, if there is an increase in intracellular (Na+) in heart failure, it is likely that the stoichiometry of NCX could be altered in failing myocytes.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, heart failure, heart disease, sodium, calcium exchange, stoichiometry.

Xu, H.B. and Z.Q. Huang (2007). Vasorelaxant effects of icariin on isolated canine coronary artery. Journal of Cardiovascular Pharmacology 49(4): 207-13. ISSN: 0160-2446.
Abstract: Owing to its cardiovascular therapeutical effects, icariin, a flavonoid isolated from Epimedii herba, is considered to be the major active constituent of Epimedii herba. The aim of this study is to investigate the effect of icariin on precontracted coronary artery isolated from canine. Coronary artery segments were isolated from normal anesthetized Beagle dogs and cut into 5-mm rings. The rings were mounted in an organ chamber and contracted by either 40 mM KCl or 10 microM PGF2alpha, and vasorelaxant tone to icariin was measured. Treatment of icariin could significantly produce a relaxation of precontracted coronary arterial rings with intact endothelium in a concentration-dependent manner. Comparatively, the vasorelaxation disappeared in denuded-endothelium rings. Furthermore, the vasorelaxant effect of icariin was blocked by Nomega-Nitro- L-arginine Methyl Ester (L-NAME), 1H-[1, 2, 4]-oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) but not by indomethacin and glibenclamide, respectively. Tetraethylammonium (TEA) could partly antagonize the vasorelaxant effect triggered by icariin. There was no significant gene expression difference of the endothelial nitric oxide synthase (eNOS) gene in coronary arterial rings among the different concentrations of icariin by RT-PCR, but the activity of eNOS was increased in a concentration-dependent manner after icariin exposure. These results suggest that icariin produces NO-dependent relaxation in the isolated canine coronary artery, and the possible mechanism is involved in the activation of eNOS protein and NO-cGMP pathway.
Descriptors: coronary vessels drug effects, drugs, chinese herbal pharmacology, flavonoids pharmacology, vasodilation drug effects, analysis of variance, anti arrhythmia agents pharmacology, coronary vessels enzymology, coronary vessels physiopathology, dinoprost pharmacology, dogs, dose response relationship, drug, endothelium, vascular drug effects, endothelium, vascular enzymology, endothelium, vascular physiopathology, enzyme inhibitors pharmacology, glyburide pharmacology, indomethacin pharmacology, models, animal, ng nitroarginine methyl ester pharmacology, nitric oxide synthase type iii drug effects, nitric oxide synthase type iii genetics, nitric oxide synthase type iii metabolism, oxadiazoles pharmacology, oxytocics pharmacology, potassium channel blockers pharmacology, quinoxalines pharmacology, rna, messenger drug effects, rna, messenger metabolism, reverse transcriptase polymerase chain reaction, tetraethylammonium pharmacology, vasodilation genetics.

Yada, T., H. Shimokawa, O. Hiramatsu, M. Goto, and F. Kajiya (2003). Protective role of hydrogen peroxide, an endogenous edhf, in ischemia-reperfusion injury in canine coronary microcirculation in vivo. Circulation 108 (17 Supplement): IV-226. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation.

Yada, T., H. Shimokawa, O. Hiramatsu, M. Goto, Y. Ogasawara, and F. Kajiya (2003). Beneficial effects of hydroxyfasudil, a specific rho-kinase inhibitor, on ischemia-reperfusion injury in canine coronary microcirculation in vivo. Circulation 108(17 Supplement): IV-226. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Descriptors: cardiovascular system, transport and circulation, pharmacology.

Yang Guirong , Zhang Wei , Wang Sujia , and Et Al (2003). Echocardiographic monitering: a chronic canine atrial fibrillation model. Zhongguo Chaosheng Yixue Zazhi 19(9): 641-643. ISSN: 1002-0101.
Abstract: Objective: To investigate the value of echocardiography in monitering a canine atrial fibrillation (AF) model with chronic rapid atrial pacing. Methods: Implantable pacemaker delivered 350apprx430 bpm stimuli to pace the right atrial appendage in 11 mongrel dogs for 8 weeks. Programmed electrical stimulation was performed before and after pacing. Changes of biatrial area and volume were assessed using echocardiography before rapid pacing and 1, 4, 8 weeks later. Results: The experiment was complete in 8 dogs. When pacemaker stopped, atrial fibrillation occurred spontaneously in 2 dogs. AF was induced by programmed stimulation in 4 dogs and by burst stimulation in 2 dogs. Biatrial area was significently enlarged after pacing 1 week while biatrial volume began to increase 4 weeks later. Mitral regurgitation and tricuspid regurgitation were noted in all dogs at the end of pacing. Conclusions: The canine model of chronic AF was established successfully. It is suggested that echocardiography be a valuable noninvasive monitoring method during the establishment.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, veterinary medicine, medical sciences, atrial fibrillation, heart disease, chronic rapid atrial pacing, heart disease, mitral regurgitation, tricuspid regurgitation, echocardiographic monitoring, clinical techniques, diagnostic techniques, implantable pacemaker, prosthetic, programmed electrical stimulation.
Language of Text: Chinese.

Yang, X.P. and S. Chiba (2003). Interaction between neuropeptide y y1 receptors and alpha1b-adrenoceptors in the neurovascular junction of canine splenic arteries. European Journal of Pharmacology 466(3): 311-315. ISSN: 0014-2999.
NAL Call Number: QP901.E8
Abstract: Previous study has demonstrated that periarterial electrical nerve stimulation (30-s trains of pulses at a frequency of 1 or 4 Hz) induces a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response in the isolated canine splenic artery. Treatment with 8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione (BMY 7378, 0.1 mumol/l), a selective alpha1D-adrenoceptor antagonist, produced a slight but significant inhibition of the second peaked responses. A marked inhibition of second peaked responses was obtained by exposure of the tissues to chloroethylclonidine (60 mumol/l), an alpha1B- and alpha1D-adrenoeptor antagonist. Neither BMY 7378 nor chloroethylclonidine affected the first peaked vasoconstrictor responses. (Leu31,Pro34)Neuropeptide Y (10-30 nmol/l), a selective neuropeptide Y Y1 receptor agonist, enhanced the second peaked responses in the presence of BMY 7378 but failed to enhance the responses in the presence of chloroethylclonidine. The results indicate that the postjunctional alpha1B-adrenoceptor subtype is likely coupled to neuropeptide Y Y1 receptors responsible for the cooperation of the sympathetic adrenergic and neuropeptide Yergic transmission in the canine splenic artery.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology.

Yao, G.H., F. Li, C. Zhang, P.F. Zhang, M. Zhang, Y.X. Zhao, X.N. Li, S.F. Ding, L. Zhong, and Y. Zhang (2007). How many planes are required to get an accurate and timesaving measurement of left ventricular volume and function by real-time three-dimensional echocardiography in acute myocardial infarction? Ultrasound in Medicine and Biology 33(10): 1572-8. ISSN: 0301-5629.
NAL Call Number: QC244.U4
Abstract: To derive the optimal cutting planes of real-time 3-D echocardiography (RT-3DE) for measuring left ventricular volume and ejection fraction (EF) in the presence of left ventricular regional wall motion abnormalities, 14 open-chest dogs were studied with RT-3DE full volume imaging and 2-D echocardiography (2DE) after left anterior descending coronary arteries were occluded for 90 min. Left ventricular end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and EF were measured off-line with 2DE and RT-3DE (2-, 4- and 8-plane) methods. The autopsy EDV was estimated by the volume of saline solution injected into the excised heart and served as the reference volume (RefV) for comparison with EDV measured by 2DE and RT-3DE. Agreement analysis was performed according to the method of Bland and Altman. There were excellent correlations between 2DE, RT-3DE (2-plane) and RT-3DE (4-plane) methods on one hand, and RT-3DE (8-plane) method on the other in the measurements of EDV, ESV and SV (r = 0.84-0.99). However, 2DE and RT-3DE (2-plane) measurements significantly underestimated RT-3DE (8-plane) (p < 0.01), whereas no significant differences between RT-3DE (4-plane) and RT-3DE (8-plane) were found in terms of EDV, ESV and SV measurements. The values of EF determined by 2DE, RT-3DE (2-plane) and RT-3DE (4-plane) methods correlated highly with that by RT-3DE (8-plane) (r = 0.82-0.98) and there was no significant difference between the two measurements. EDV values determined by 2DE, RT-3DE (2-plane), RT-3DE (4-plane) and RT-3DE (8-plane) correlated highly with RefV (r = 0.84, r = 0.92, r = 0.94 and r = 0.97, respectively) and there was no significant difference between RefV and EDV by RT-3DE (4-plane) and RT-3DE (8-plane). In contrast, EDV measured by 2DE and RT-3DE (2-plane) methods underestimated RefV significantly (p < 0.01). In conclusion, RT-3DE allows reliable and reproducible measurement of left ventricular volume and EF, even in the presence of left ventricular regional wall motion abnormalities. RT-3DE (4-plane) is the method of choice for an accurate and timesaving quantification of left ventricular volume and function.
Descriptors: echocardiography, three dimensional methods, myocardial infarction ultrasonography, ventricular dysfunction, left ultrasonography, dogs, echocardiography, heart ventricles ultrasonography, animal models.

Yeh, H.I., Y.J. Lai, Y.N. Lee, Y.J. Chen, Y.C. Chen, C.C. Chen, S.A. Chen, C.I. Lin, and C.H. Tsai (2003). Differential expression of connexin43 gap junctions in cardiomyocytes isolated from canine thoracic veins. Journal of Histochemistry and Cytochemistry 51(2): 259-266. ISSN: 0022-1554.
NAL Call Number: 381 J8222
Abstract: We investigated the phenotypic features of cardiomyocytes, including the gap junctions, in the myocardial sleeve of thoracic veins. Single cardiomyocytes, isolated from the canine pulmonary veins (PV) and superior vena cava (SVC) using digestive enzymes, were examined by immunoconfocal microscopy using antisera against connexin43 (Cx43), Cx40, and other cell markers. The results showed that isolated cardiomyocytes displayed rod shapes of various sizes, ranging from <50 mum to >200 mum in length, and all the cells expressed alpha-actinin and vinculin. Gap junctions made of various amounts of Cx43 and Cx40 were found at the cell borders. These two connexins were extensively co-localized. Comparison between the thoracic veins showed that cells of the SVC contained more Cx43 gap junctions (total Cx43 gap junctions area per cell surface area, 4.0+-0.2% vs 1.5+-0.2%; p<0.01). In addition, for single-nucleus cells, those from the PV were longer (103.7+-3.6 vs 85.0+-3.1 mum; p<0.01) but narrower (14.4+-0.5 vs 16.9mu0.9 mum; p<0.01). In conclusion, canine thoracic veins contain cardiomyocytes with differences in shape and gap junctions, suggesting that the electrical conduction properties may be different between the thoracic veins.
Descriptors: cardiovascular system, transport and circulation, cell biology, immunoconfocal microscopy, imaging and microscopy techniques, immunologic techniques, laboratory techniques.

Yelmen, N.K., G. Sahin, and T. Oruc (2004). The effects of vagal stimulation on laryngeal vascular resistance and intraluminal pressure in the dog. Tohoku Journal of Experimental Medicine 202(4): 283-294. ISSN: 0040-8727.
Abstract: In anaesthetized dogs (sodium pentobarbitone 30 mg/kg, i.v.) laryngeal vascular resistance was measured by unilateral perfusion at constant flow of the branch of the cranial superior thyroid artery that supplies the larynx. Arterial perfusion was at constant flow and inflow pressure was divided by flow to give laryngeal vascular resistance (RLV). Intraluminal laryngeal pressure (PL) and systemic arterial blood pressure (BP) were also measured. Stimulation (20 V, 20 Hz, 0.2 milliseconds) of the central end of cervical vagus caused an increase in RLV (+22.9+/-6.1%) and a decrease in PL (-12.1+/-4.4%). Stimulation (10 V, 10 Hz, 0.2 milliseconds) of the central end of the recurrent laryngeal nerve (RLN) reduced RLV (-3.4+/-0.8%) and PL (-7.5+/-4.1%). Stimulation of the peripheral end of the RLN decreased RLV (-7.1+/-1.9%) and increased PL (+21.6+/-7.7%). Stimulation of the central end of the superior laryngeal nerve (SLN) increased RLV (+17.9+/-3.2%) and PL (+59.8+/-2.7%), whereas stimulation of the peripheral end of the SLN decreased RLV (-4.8+/-1.6%) and PL (-4.1+/-2.4%). After treatment with alpha-adrenoreceptor antagonist phentolamine (0.5 mg/kg, Lv.), stimulation of the central end of cervical vagus nerve reduced RLV by 25% and decreased BP. Phentolamine caused a decrease in BP and reduced the magnitude of increase in RLV in response to stimulation of central end of SLN. After atropine sulphate (0.5-2.0 mg/kg, i.v.), the stimulation of both central and peripheral ends of RLN reduced RLV. The decrease in RLV during stimulation of peripheral end of SLN was reduced by atropine. Thereafter, pancuronium bromide (0.06-0.1 mg/kg, i.v.) was given and dogs were artifically ventilated. After paralyzed, stimulation of the central end of the SLN decreased RLV (+26.0+/-4.5%) but produced no change in PL. It is concluded that parasympathetic motor fibers in the RLN and SLN are effective for the laryngeal vascularity and non-adrenergic system may be responsible for laryngeal vasoconstriction.
Descriptors: cardiovascular system, transport and circulation, methods and techniques, vagal stimulation, clinical techniques, therapeutic and prophylactic techniques, intraluminal pressure, laryngeal vascular resistance, systemic arterial blood pressure.

Yelmen, N.K., G. Sahin, T. Oruc, and M. Hacibekiroglu (2003). Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs. Chinese Journal of Physiology 46(1): 27-33. ISSN: 0304-4920.
Abstract: The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O2-93% N2) gas mixtures and on the injection of KCN (80 mug/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pHa values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P<0.001, P<0.001, P<0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P<0.001, P<0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P<0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia.
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, respiratory system, respiration, veterinary medicine, medical sciences, hypoxia, respiratory system disease, pulmonary hypertension, chemodenervation, experimental surgical techniques, laboratory techniques, pulmonary arterial pressure [pap].

Yu, S., Y. Ma, T. Xia, and S. Ma (1995). Studies of action of rhodobrun roseum limpr on changes of red cell aggregation and yield-shear stress in dogs with acute experimental coronary occlusion. Zhongguo Zhongyao Zazhi 20(7): 429-431, 449. ISSN: 1001-5302.
Abstract: Following acute occlusion of the left anterior descending coronary artery in dogs, significant increases were observed in the red cell aggregation index, yield-shear stress and red cell electrophoretic time in blood drained from ischemic area. When transfusion was performed with Rhodobrum roseum solution from the right femoral vein, significant rises of the above-said items were observed.
Descriptors: biochemistry and molecular biophysics, blood and lymphatics, transport and circulation, cardiovascular system, transport and circulation, cell biology, pharmacognosy, pharmacology, blood viscosity, myocardial ischemia.
Language of Text: Chinese.

Zhang, J., Z. Chen, F.R. Cobb, and J.S. Stamler (2004). Role of mitochondrial aldehyde dehydrogenase in nitroglycerin-induced vasodilation of coronary and systemic vessels - an intact canine model. Circulation 110(6): 750-755. ISSN: 0009-7322.
NAL Call Number: RC681.A1 C8
Abstract: Background-It has recently been shown that mitochondrial aldehyde dehydrogenase 2 (mtALDH) catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from nitroglycerin (glyceryl trinitrate (GTN)) within mitochondria, leading to production of cGMP and vasorelaxation. However, whether this mechanism operates in the systemic and coronary beds that subserve the antianginal action of GTN is not known. In this study, we address this question in an intact canine model. Methods and Results-Fourteen healthy mongrel dogs (weight, 20 to 25 kg) were studied. Coronary blood flow and hemodynamics were continuously monitored by a pulse Doppler flow probe implanted around the left circumflex coronary artery and with catheters in left ventricle and aorta, respectively. Each dog was given a 1-mL bolus injection of GTN, sodium nitroprusside (SNP), or adenosine through a catheter in the left atrium before and 30 minutes after infusion of cyanamide (17 mg/kg), an inhibitor of mtALDH. Cyanamide significantly inhibited both the classic dehydrogenase and GTN reductase activities of mtALDH in situ and attenuated the coronary blood flow increase and declines in blood pressure and left ventricular end-diastolic pressure produced by GTN in vivo. In contrast, mtALDH inhibition had no effect on the coronary and systemic effects of SNP and adenosine. Conclusions-Our data suggest that mtALDH contributes to GTN biotransformation in vivo and thus at least partly underlies the antianginal mechanism of drug action. Our findings also highlight the differences in biometabolism of clinically relevant nitrosovasodilators.
Descriptors: cardiovascular system, transport and circulation, pharmacology.

Zhang Shunye , Sun Zongquan , Liu Lixin , and Hasichaonu (2003). Carvedilol attenuates cpb-induced apoptosis in dog heart: regulation of fas/fasl and caspase-3 pathway. Chinese Medical Journal (English Edition) 116(5): 761-766. ISSN: 0366-6999.
Abstract: Objective: To evaluate the effects of Carvedilol on cardiopulmonary bypass (CPB)-induced myocardiocyte apoptosis and its effects on regulation of Fas, FasL expression, caspase-3 activity and oxidative stress in the left ventricle (LV) in this setting. Methods: Ten adult dogs undergoing conventional hypothermic CPB were randomly divided into control and Carvedilol treated groups (n=5, respectively). Dogs in Carvedilol treated group received a bolus of Carvedilol (1 mg/kg) intravenously and a maintenance dosage of Carvedilol (3 mugcntdotmin-1cntdotkg-1) for 3 hours after the reperfusion of the heart. Dogs in control group received no Carvediolol. LV samples were obtained before, during and 3 hours after CPB. In situ nick end-labeling (TUNEL) technique was used to detect the apoptotic cells. The expressions of Fas and FasL were detected immunohistochemically and quantified by fluorescence activated cell sorting (FACS). The activity of caspase-3 enzyme and malondialdehyde (MDA) level were measured by cleavage of Z-DEVD-AMC substrate and thiobarbituric acid reactive substance (TBARS) method, respectively. Results: Before and during CPB, all the parameters were not significantly different intra- or between groups (P>0.05). After CPB, these parameters in both groups were significantly elevated compared with those of before and during CPB (P<0.028, respectively). However, the number of apoptotic cells in Carvedilol treated group was significantly decreased compared with that of the control group (P<0.021). The expressions of Fas and FasL were significantly downregulated by Carvedilol (P<0.001 and 0.003, respectively). The caspase-3 activity and the content of MDA in the Carvedilol treated group was also significantly reduced (P<0.026 and 0.005, respectively). Conclusions: Carvedilol significantly reduces CPB-induced cardiomyocyte apoptosis in dog hearts and the reduction of cardiomyocyte apoptosis is associated with downregulation of Fas and FasL expression, inhibition of caspase-3 activity and oxidative stress in LV.
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, pharmacology, surgery, medical sciences, tunel, genetic techniques, laboratory techniques, cardiopulmonary bypass, clinical techniques, therapeutic and prophylactic techniques, apoptosis, oxidative stress.

Zhang, X., S. Kinugawa, and T. Hintze (2004). Impaired endothelial nitric oxide production from coronary microvessels induced by camp signal transduction in diabetic dog heart. FASEB Journal 18(4-5): Abst. 201.6. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: biochemistry and molecular biophysics, cardiovascular system, transport and circulation, endocrine system, chemical coordination and homeostasis, diabetes, endocrine disease, pancreas, metabolic disease, cyclic amp signal transduction, posttranslational problem.

Zhou, S., B.C. Jung, A.Y. Tan, V.Q. Trang, G. Gholmieh, S.W. Han, S.F. Lin, M.C. Fishbein, P.S. Chen, and L.S. Chen (2008). Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a canine model of sudden death. Heart Rhythm the Official Journal of the Heart Rhythm Society 5(1): 131-9. ISSN: 1547-5271.
Abstract: BACKGROUND: Little information is available on the temporal relationship between instantaneous sympathetic nerve activity and ventricular arrhythmia in ambulatory animals. OBJECTIVE: The purpose of this study was to determine if increased sympathetic nerve activity precedes the onset of ventricular arrhythmia. METHODS: Simultaneous continuous long-term recording of left stellate ganglion (LSG) nerve activity and electrocardiography was performed in eight dogs with nerve growth factor infusion to the LSG, atrioventricular block, and myocardial infarction (experimental group) and in six normal dogs (control group). RESULTS: LSG nerve activity included low-amplitude burst discharge activity (LABDA) and high-amplitude spike discharge activity (HASDA). Both LABDA and HASDA accelerated heart rate. In the experimental group, most ventricular tachycardia (86.3%) and sudden cardiac death were preceded within 15 seconds by either LABDA or HASDA. The closer to onset of ventricular tachycardia, the higher the nerve activity. The majority of HASDA was followed immediately by either ventricular arrhythmia (21%) or QRS morphology changes (65%). HASDA occurred in a circadian pattern. HASDA occurred twice as often in the experimental group than in the control group. Electrical stimulation of LSG increased transmural heterogeneity of repolarization (Tpeak-end intervals) and induced either ventricular tachycardia or fibrillation in the experimental group but not in the control group. Immunohistochemical studies revealed increased synaptogenesis and nerve sprouting in the LSG in the experimental group. CONCLUSION: Two distinct types of LSG nerve activity (HASDA and LABDA) are present in the LSG of ambulatory dogs. The majority of malignant ventricular arrhythmias are preceded by either HASDA or LABDA, with HASDA particularly arrhythmogenic.
Descriptors: death, sudden, cardiac prevention and control, stellate ganglion physiology, sympathetic nervous system physiopathology, tachycardia, ventricular physiopathology, ventricular fibrillation physiopathology, dogs, electric stimulation, electrocardiography, electrophysiology, heart rate, models, animal, tachycardia, ventricular etiology, time factors, ventricular fibrillation etiology.
Notes: Comment In: Heart Rhythm. 2008 Jan;5(1):140-1.

Zhu, B.M., S. Miyamoto, Y. Nagasawa, T. Wajima, and K. Hashimoto (2003). Effect of the sarcolemmal katp channel blocker hmr1098 on arrhythmias induced by programmed electrical stimulation in canine old myocardial infarction model: comparison with glibenclamide. Journal of Pharmacological Sciences 93(1): 106-113. ISSN: 1347-8613.
Abstract: The blockade of myocardial KATP channels may be antiarrhythmic for ischemic arrhythmias. A new sulfonylthiourea, HMR1098 (1-(15-(2-(5-chloro-o-anisamido)ethyl)-2-methoxyphenylsulfonyl)-3-methylthiourea, sodium salt), was demonstrated to be a cardioselective KATP-channel antagonist and to suppress arrhythmias during acute ischemia. We investigated effects of HMR1098 on the arrhythmias induced by programmed electrical stimulation (PES) in a canine old myocardial infarction model. HMR1098 (3 mg/kg, i.v.) significantly improved the scores of PES-induced ventricular arrhythmias, without changing the blood glucose concentrations. A classical sulfonylurea, glibenclamide (1 mg/kg, i.v.), had no significant effects on these arrhythmias, but reduced the blood glucose and increased the plasma insulin concentrations.
Descriptors: cardiovascular system, transport and circulation, pharmacology, ischemic arrhythmia, heart disease, vascular disease, old myocardial infarction, heart disease, programmed electrical stimulation induced ventricular arrhythmia, heart disease.

Ziba, T., C.W. Smith, and C.A. Rivera (2004). Detection of extra-nuclear high mobility group box-1 protein in a canine model of myocardial infarction. FASEB Journal 18(4-5): Abst. 670.16. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: box-1 protein (HMGB-1), nuclear protein , biochemistry and molecular biophysics, cardiovascular system, transport and circulation, myocardial infarction, heart disease, vascular disease

Zong, P., S. Setty, W. Sun, J.D. Tune, and H.F. Downey (2004). Alpha -adrenergic right coronary vasoconstriction forces mobilization of right ventricular oxygen extraction reserve in exercising dogs. FASEB Journal 18(4-5): Abst. 200.1. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation.

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