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

Bartoli, C.R., I. Akiyama, K. Okabe, E.A. Diaz, and J.J. Godleski (2008). Permanent tracheostomy for long-term respiratory studies. Journal of Surgical Research 145(1): 124-9. ISSN: 0022-4804.
Abstract: BACKGROUND: We describe a modified surgical technique for permanent, anterior tracheal-wall stoma for chronic, repeat respiratory studies in trained, conscious dogs. These cannula-free tracheostomies require minimal daily maintenance, permit repeat intubation with endotracheal tubes modified for airflow respiratory measurement, and facilitate up to 6 h continuous administration of aerosol agents during long-term or repeat respiratory studies. METHODS: In 20 dogs, during a 30 to 40 min procedure, portions of tracheal rings 2-4 were removed to create an oval stoma, approximately 2 x 1 cm. The dermis was secured to the transected cartilage and tracheal mucosa in such a manner that skin covered the sternohyoid muscles and grew-in flush with the tracheal mucosa at the stomal opening. Stomas were cleaned daily, and fur was clipped weekly around the stomal site. No other maintenance procedures or environmental modifications were needed. Animals breathed through both the stoma and the upper airway and barked normally. RESULTS: Stomas remained viable in long-term animals (n = 4) ongoing for 70.3 +/- 32.2 mo (mean +/- SEM), with an ongoing maximum of 126 mo. Postmortem examinations were performed on shorter-term animals (n = 16) sacrificed at 16.7 +/- 7.3 mo. Thirteen showed no appreciable tracheal stenosis and three showed <10% stenosis at the level of the stoma. Histopathological examination of the stomal opening and surrounding tissue revealed minimal chronic inflammation and no evidence of necrosis or infection. CONCLUSIONS: During long-term respiratory studies, this practical and dependable tracheal stoma provides a means for examining acute and chronic effects of environmental and pathophysiological influences on the respiratory system of conscious dogs.
Descriptors: surgical stomas pathology, trachea pathology, trachea surgery, tracheostomy methods, aerosols administration and dosage, dogs, inflammation pathology, intubation, intratracheal, models, animal, postoperative care methods, respiratory function tests, respiratory system physiopathology, tracheal stenosis pathology.

Bilotta, F., L. Agati, V. Fabbrini, G. Centola, and G. Rosa (2003). Pulmonary transit of levovist(r): a transthoracic echocardiographic study. 2003 Annual Meeting of the American Society of Anesthesiologists, San Francisco, CA, USA; October 11-15, 2003,
Online: http://www.asa-abstracts.com
Abstract: After intravenous injection in spontaneously breathing patients and anesthetized dogs, ultrasound contrast agents opacify the right ventricle, pass through the lungs, opacify the left ventricle and depict systemic organ perfusion patterns. Contrast ultrasound based intraoperative organ-perfusion studies -- currently limited to intraarterial or intraaortic injection -- require an intravenous ultrasound contrast agent that passes through the lungs during mechanical ventilation in humans. Effective lung transit of ultrasound contrast agents during controlled mechanical ventilation is a prerequisite for ultrasound-based real time systemic organ perfusion studies (myocardium, kidneys, liver and brain) because it allows the contrast agent injected intravenously to reach the systemic circulation. Whether an ultrasound contrast agent passes the lungs during mechanical ventilation depends on many factors, including biochemical interactions with blood gasses, intravascular pressure and shell stability. Mechanical ventilation alters the physiology of the pulmonary microcirculation by increasing intrathoracic pressure and pulmonary vascular resistance. Levovist(R) (Schering AG, Berlin, Germany) is a galactose and palmitic based air-filled ultrasound contrast agent used for organ perfusion studies with intravenous injection in spontaneously breathing patients. In this study, we investigated whether Levovist(R) injected intravenously during intermittent positive pressure ventilation (IPPV) opacifies the right and left ventricular cavities after lung transit. With transthoracic echocardiography we measured the time in cardiac cycles (CC), for contrast to appear in the right ventricle and traverse the lungs; and the intensity of right and left ventricular cavity opacification (RVCO and LVCO). Twenty patients undergoing elective peripheral neurosurgical procedures were prospectively enrolled. All patients received intravenous Levovist(R) 1 g, during spontaneous breathing (baseline), 5 min after the beginning of IPPV, and 5 min and 30 min after extubation. Pulmonary transit time was constant: 7 +- 3 CC at baseline, 6 +- 2 CC during IPPV, and 8 +- 2 CC at 5 min and 7 +- 3 CC at 30 min after extubation. In all patients, each of the four contrast injections achieved high-grade RVCO and LVCO, and remained constant before, during IPPV and at 5 and 30 minutes after extubation. In this study, conducted in patients mechanically ventilated during general anesthesia for peripheral neurosurgical procedures, intravenous injection of Levovist(R) during IPPV opacified the right ventricular cavity, passed physiologically through the lungs and opacified the left ventricular cavity. It did so at an intensity equivalent to that when patients breathed spontaneously. During surgery, especially in high-risk patients, adequate organ blood flow is critical for normal cellular metabolism and tissue preservation. Because hypoperfusion often precedes and causes functional damage, early diagnosis of inadequate tissue perfusion could guide treatment to restore perfusion. In conclusion, Levovist(R) injected intravenously provides physiologic pulmonary capillary transit in patients undergoing peripheral neurosurgical procedures during mechanical ventilation. An ultrasound contrast agent with these properties might make real-time echographic evaluation of organ perfusion patterns possible in patients during IPPV. Anesthesiology 2003; 99: A168.
Descriptors: methods and techniques, pharmacology, surgery, medical sciences, contrast ultrasound, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, mechanical ventilation, therapeutic and prophylactic techniques, transthoracic echocardiography, cardiac cycles.

Black, B.A., J.R. Moore, O.B. Wilson, R.D. Hubmayr, and A.M. Boriek (2002). Mechanics and kinematics of the midcostal diaphragm and lower rib cage in dogs. FASEB Journal 16(5): A878. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: muscular system, movement and support, respiratory system model, beagle dogs, respiration, lung volume, skeletal system, movement and support, meeting abstract.

Blanch, L., T.E. Van der Kloot, A.M. Youngblood, A.B. Adams, A. Naveira, G. Murias, P.V. Romero, and A. Nahum (2001). Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury. Critical Care Medicine 29(12): 2251-7. ISSN: 0090-3493.
Abstract: OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).
Descriptors: adult, mixed-breed, lung injury, lung function, tracheal gas insufflation (TGI), partial liquid ventilation (PLV).

Bof, A.M., A. Rapoport, D.N. Paulo, L.C. Leiro, M.R. Gomes, and R.R. Pando Serrano (2007). Comparative study of the resistance of manual and mechanical sutures in the bronchial stump of dogs submitted to left pneumonectomy. Jornal Brasileiro De Pneumologia Publicacao Oficial Da Sociedade Brasileira De Pneumologia e Tisilogia 33(2): 141-7.
Abstract: OBJECTIVE: To compare the resistance of manual suture with that of mechanical suture immediately after the suture of the left bronchial stump of dogs submitted to pneumonectomy. METHODS: A total of 15 mixed-breed dogs of both genders, each weighing between 8 and 23 kg, were randomly divided into 2 groups. In group I (n = 7), the bronchial stump was sutured manually (the Sweet method) and, in group II (n = 8), it was stapled. Immediately after the closure of the bronchial stump, the intratracheal pressure was progressively increased in a controlled manner. RESULTS: The mean rupture pressure of the bronchial stump suture line was 33.71 mmHg in group I and 89.87 mmHg in group II (p < 0.01). CONCLUSION: These data allowed us to conclude that mechanical suture of the bronchial stump, submitted to pressure immediately after closure, is more resistant than is manual suture in dogs submitted to pneumonectomy.
Descriptors: bronchi surgery, pneumonectomy methods, suture techniques adverse effects, sutures adverse effects, data interpretation, statistical, dogs, models, animal, pressure, random allocation, surgical stapling.
Language of Text: Portuguese.

Brimioulle, S., V. Julien, R. Gust, J.K. Kozlowski, R. Naeije, and D.P. Schuster (2002). Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury. Critical Care Medicine. 30(4): 874-80. ISSN: 0090-3493.
Abstract: OBJECTIVE: To investigate the role of hypoxic pulmonary vasoconstriction in the intrapulmonary blood flow redistribution and gas exchange protection during oleic acid acute lung injury. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Three groups of five mongrel dogs. INTERVENTIONS: Induction of acute lung injury by 0.08 mL/kg oleic acid intravenously. Hypoxic pulmonary vasoconstriction inhibition by Escherichia coli endotoxin microdose (15 microg/kg) pretreatment or by metabolic alkalosis (pH 7.60). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial and venous resistances were determined by flow-pressure curves and by capillary pressure estimation. Regional lung water and pulmonary blood flow were assessed by positron emission tomography. Oleic acid alone increased the arterial and venous resistances, redistributed blood flow away from edematous areas, and decreased the Pao2 from 507 +/- 16 to 373 +/- 60 torr. on Fio2 1.0 and positive end-expiratory pressure 5 cm H2O. Endotoxin pretreatment inhibited the increase in arterial resistance, suppressed the redistribution, and decreased the Pao2 to 105 +/- 22 torr. Alkalosis inhibited the increase in arterial and venous resistances, suppressed the redistribution, and decreased the Pao2 to 63 +/- 12 torr. Reversal of the alkalosis increased the arterial and venous resistances, restored the perfusion redistribution, and improved the Pao2 to 372 +/- 63 torr. Changes in blood gases conformed to predictions of a computer lung model in which hypoxic pulmonary vasoconstriction was suppressed by endotoxin and alkalosis. CONCLUSIONS: We conclude that in oleic acid-induced lung injury, a) pulmonary hypertension results from increases in both arterial and venous resistances; b) the increase in arterial resistance is the primary mechanism responsible for the perfusion redistribution and the gas exchange protection; and c) the increase in arterial resistance is most consistent with hypoxic pulmonary vasoconstriction.
Descriptors: hypoxic pulmonary vasoconstriction, intrapulmonary blood flow, oleic acid, acute lung injury, arterial resistance, venous resistance.

Brogan, T.V., H.T. Robertson, W.J.E. Lamm, J.E. Souders, and E.R. Swenson (2003). Effect of inspired co2 on va/q matching in dogs as measured by microspheres. Pediatric Research 53(4 Part 2): 49A. ISSN: 0031-3998.
NAL Call Number: RJ1.P4
Descriptors: respiratory system, respiration, miget, v a, q matching, microspheres, perfusion, sites of action, ventilation .

Cappello, M., C. Yuehua, and A. De Troyer (1995). Rib cage distortion in a canine model of flail chest. American Journal of Respiratory and Critical Care Medicine 151(5): 1481-1485. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: Although blunt chest injuries frequently lead to respiratory failure, the effects of flail chest on the mechanics of breathing have not been evaluated. In the present studies, we have measured the respiratory displacements of the ribs and sternum and the electromyograms (EMG) of the parasternal and external intercostal muscles in eight supine, anesthetized, spontaneously breathing dogs before and after the third to sixth ribs on the right side of the chest were fractured both dorsally and ventrally. After flail, the fractured ribs moved inward, rather than outward, during inspiration, but their inspiratory cranial displacement remained unchanged. The inspiratory outward and caudal displacement of the sternum, the inspiratory EMG activity of the parasternal intercostals, the pattern of breathing, and the arterial blood gases were also unaltered. However, the inspiratory EMG activity recorded from the external intercostals increased consistently to 327 +- 101% of control (p lt 0.05). These observations indicate that with flail chest, the disconnected segment of the rib cage shows paradoxical motion exclusively along the lateral axis; the increased external intercostal activation may account, at least in part, for the persistent inspiratory cranial motion of the ribs. These observations also suggest that the harmful effects of blunt chest injuries are related to pulmonary contusion and pain, rather than to flail chest per se.
Descriptors: animal care, respiratory system, respiration .

Casal, M., S. Ryan, J. Rhodes, and J. Scheidt (2003). Immunological aspects of x-linked ectodermal dysplasia: a dog model for the human disease. American Journal of Human Genetics 73(5): 454. ISSN: 0002-9297.
NAL Call Number: QH431.A1A54
Descriptors: molecular genetics, biochemistry and molecular biophysics, X linked ectodermal dysplasia, genetic disease, immune system disease, integumentary system disease, respiratory system disease, genetics, immunology, pathology, transmission, pulmonary disorders, respiratory system disease, respiratory tract infection, infectious disease, cytokine production, immune system defects, immunological aspects, systemic, localized humoral, cellular responses.

Chhetri, D.K., B. Jahan Parwar, S.D. Hart, S.M. Bhuta, and G.S. Berke (2004). Injection laryngoplasty with calcium hydroxylapatite gel implant in an in vivo canine model. Annals of Otology Rhinology and Laryngology 113(4): 259-264. ISSN: 0003-4894.
Abstract: The ideal injectable agent for vocal fold medialization is biocompatible, durable, sized to prevent phagocytosis and migration, and formulated for easy injection and does not adversely affect the viscoelastic properties of the vocal fold. We tested a cohesive implant of calcium hydroxylapatite (CaHA) particles in a gel carrier in an in vivo canine model of phonation. Six dogs underwent unilateral recurrent laryngeal nerve section and injection laryngoplasty of the paralyzed vocal fold with a CaHA implant. The six follow-up examinations were performed at 1, 2, 3, 6, 9, and 12 months, and the larynx and bilateral neck lymphatic system were harvested for histologic analysis. The CaHA implant adequately medialized the vocal fold to regain glottal closure. The mucosal waves remained unaltered from baseline. The implant remained soft in the larynx and did not migrate to the neck lymphatic system. A localized foreign body giant cell reaction was present on histologic evaluation, but not acute or other chronic inflammation. A size analysis revealed no resorption of the CaHA particles. A decrease in medialization was noted at all follow-up intervals related to resorption of the aqueous-based gel carrier. The CaHA implant appears to be relatively safe and suitable for injection laryngoplasty.
Descriptors: equipment apparatus devices and instrumentation, methods and techniques, nervous system, neural coordination, respiratory system, respiration, calcium hydroxylapatite gel implant, prosthetic, histologic analysis, histology and cytology techniques, laboratory techniques, injection laryngoplasty, clinical techniques, therapeutic and prophylactic techniques, unilateral recurrent laryngeal nerve section, experimental surgical techniques, vocal fold paralysis, experimental surgical techniques, cell migration, phagocytosis, phonation .

Chino, K., C.K. Choong, P.D. Toeniskoetter, J.D. Cooper, H.F. Lausberg, K.T. Bae, and J.A. Pierce (2004). A canine model for production of severe unilateral panacinar emphysema. Experimental Lung Research 30(4): 319-332. ISSN: 0190-2148.
Abstract: The authors created a canine model of severe emphysema using whole lung lavage to deliver repeated porcine pancreatic elastase solution to the terminal airways and alveoli of the right lung. This model produces extreme unilateral panacinar emphysema closely resembling that encountered in patients with alpha1-antitrypsin deficiency. Because the contralateral lung remains functional, the animals can be maintained indefinitely. The model will be of value in developing imaging techniques capable of safely evaluating the effect of treatment on panacinar emphysema in alpha 1 -antitrypsin-deficient patients.
Descriptors: respiratory system, respiration, unilateral panacinar emphysema, respiratory system disease.

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.

Criner G J , Muza S R , and Kelsen S G (1990). Inspiratory action on the rib cage by the canine pectoral muscles. American Review of Respiratory Disease 141(4 PART 2): A170. ISSN: 0003-0805.
NAL Call Number: RC705 .A4
Descriptors: muscular system, movement and support, respiratory system, respiration, skeletal system, movement and support, abstract

Dane, D.M., X. Yan, R.M. Tamhane, R.L.J. Johnson, A.S. Estrera, D.C. Hogg, R.T. Hogg, and C.C.W. Hsia (2004). Retinoic acid-induced alveolar cellular growth does not, improve function after right pneumonectomy. Journal of Applied Physiology 96(3): 1090-1096. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Abstract: To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n=4) received 2 mgcntdotkg-1cntdotday-1 po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n=4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (Vtiss-RB) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (Vair-CT and Vtiss-CT) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas Vtiss-RB was significantly lower at both lung volumes in RA-treated animals, Vair-CT and Vtiss-CT were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.
Descriptors: methods and techniques, pharmacology, respiratory system, respiration, right pneumonectomy, experimental surgical techniques, laboratory techniques, alveolar cellular growth, cardiac output, diffusing capacity for carbon monoxide, lung air, lung function, lung volume, resting pulmonary function, septal volume, tissue volume, transpulmonary pressure.

Decramer M , Reid M B , and De Troyer A (1985). Relationship between parasternal intercostal length and rib cage displacement in dogs. Journal of Applied Physiology 58(5): 1517-1520. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Abstract: The relationship between parasternal intercostal length and rib cage cross-sectional area was examined in 9 supine dogs during passive inflation and during quiet breathing before and after phrenicotomy. Parasternal intercostal length (PSL) was measured with a sonomicrometry technique and rib cage cross-sectional area (Arc) was measured with a Respitrace coil placed around the middle rib cage. During active inspiration as well as during passive inflation, PSL decreased as Arc increased. However, the relationship between PSL and Arc during active inspiration, whether in the intact or phrenicotomized animal, was almost invariably different from that during passive inflation, so that the same increase in Arc was associated with a greater decrease in PSL in the former than in the latter instance. This difference between passive inflation and active inspiration was probably due to the active contraction of the parasternals during inspiration and the consequent caudal displacement of the sternum. In upright humans, the sternum moved cephalad and not caudad during inspiration, so the relationship between PSL and Arc during active breathing might be similar to that during passive inflation.
Descriptors: muscular system, movement and support, nervous system, neural coordination, respiratory system, respiration, surgery, medical sciences, respiratory muscle passive inflation active inspiration.

Denault, A.Y., J.3. Gorcsan, and M.R. Pinsky (2001). Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations. Journal of Applied Physiology 91(1): 298-308. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Abstract: Positive-pressure ventilation (PPV) may affect left ventricular (LV) performance by altering both LV diastolic compliance and pericardial pressure (Ppc). We measured the effect of PPV on LV intraluminal pressure, Ppc, LV volume, and LV cross-sectional area in 17 acute anesthetized dogs. To account for changes in lung volume independent of changes in Ppc and differences in contractility, measures were made during both open- and closed-chest conditions, during closed chest with and without chest wall binding, and after propranolol-induced acute ventricular failure (AVF). Apneic end-systolic pressure-volume relations (ESPVR) were generated by inferior vena caval occlusions. With the open chest, PPV had no effects. With the chest closed, PPV inspiration decreased LV end-diastolic volume (EDV) along its diastolic compliance curve and decreased end-systolic volume (ESV) such that the end-systolic pressure-volume domain was shifted to a point left of the LV ESPVR, even when referenced to Ppc. The decrease in EDV was greater in control than in AVF conditions, whereas the shift of the ESV to the left of the ESPVR was greater with AVF than in control conditions. We conclude that the hemodynamic effects of PPV inspiration are due primarily to changes in intrathoracic pressure and that the inspiration-induced decreases of LV EDV reflect direct effects of intrathoracic pressure on LV filling. The decreases in LV ESV exceed the amount explained solely by a reduction in LV ejection pressure.
Descriptors: physiology, positive pressure ventilation, anesthetized dogs, diastolic pressure, pericardial pressure, intraluminal pressure.

Dias Junior, C.A., J.T. Sertorio, and J.E. Tanus Santos (2007). Aminoguanidine produces beneficial haemodynamic effects in a canine model of acute pulmonary thromboembolism. Acta Physiologica Oxford, England 191(3): 189-96. ISSN: 1748-1708.
NAL Call Number: QP1 .A2
Abstract: AIM: Activating the nitric oxide (NO)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway improves haemodynamics following acute pulmonary thromboembolism (APT). However, the role of NO synthase (NOS) isoforms in the responses to APT has not been determined. We examined the effects of selective and non-selective inducible NOS (iNOS) inhibition. METHODS: Haemodynamic evaluations were performed in non-embolized dogs treated with saline (control group; n = 4), L-NAME (NAME group; n = 3), or aminoguanidine (AG group; n = 3), and in dogs that received the same drugs and were embolized with 5 mL kg(-1) of clots made with autologous blood (Emb group, n = 9; NAME + Emb group, n = 4 and AG + Emb group, n = 7). The lung concentrations of nitrite/nitrate (NOx) and cGMP were determined by chemiluminescence and ELISA respectively. RESULTS: Acute pulmonary thromboembolism increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 21.4 +/- 1.7 mmHg and by 843 +/- 34 dyn s cm(-5) m(-2), respectively, in Emb group. MPAP and PVRI increased to higher levels in the NAME + Emb group 15 min after APT and all dogs in this group died 15-30 min after APT. Conversely, lower MPAP and PVRI levels were found in the AG + Emb group 2 h after APT compared with the Emb group (both P < 0.05). Higher NOx concentrations were found in the Emb group compared with the other groups (all P < 0.05). Higher cGMP concentrations were found in the Emb and AG + Emb groups compared with the other groups (all P < 0.05). CONCLUSIONS: These results indicate that endogenous NO protects against APT-induced cardiovascular responses. Moreover, iNOS-derived NO possibly produces unfavourable effects, which are counteracted by aminoguanidine. However, non-NO-related mechanisms may also be involved.
Descriptors: guanidines therapeutic use, nitric oxide synthase type ii antagonists and inhibitors, pulmonary embolism drug therapy, acute disease, blood pressure drug effects, cyclic gmp analysis, cyclic gmp metabolism, dogs, lung chemistry, lung metabolism, models, animal, ng nitroarginine methyl ester metabolism, ng nitroarginine methyl ester therapeutic use, nitrates analysis, nitrates metabolism, nitric oxide metabolism, nitric oxide synthase type ii metabolism, pulmonary embolism metabolism, vascular resistance drug effects.

Downie, J.M., A.J. Nam, and B.A. Simon (2004). Pressure-volume curve does not predict steady-state lung volume in canine lavaae lung injury. American Journal of Respiratory and Critical Care Medicine 169(8): 957-962. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: To better understand strategies for recruiting and maintaining lung volume in acute lung injury, we examined relationships between steady-state lung volume and cumulative cyclic recruitment/ derecruitment volume history and the quasi-static pressure-volume curve, in an animal saline lavage lung injury model. Small-volume tidal pressure-volume loops performed after inflation from functional residual capacity demonstrated incremental, cyclic recruitment only if the peak pressure achieved exceeded the pressure at which the compliance increased (Pflex) on the pressure-volume curve, whereas loops performed after deflation from total lung capacity remained close to the envelope deflation curve. Recruitment continued to occur up to and beyond a peak inspiratory airway pressure of 40 cm H2O, as demonstrated by both the tidal loops and by computed tomography-derived lung volume data. Tidal-specific compliance was relatively constant across positive end-expiratory pressure levels after inflation from functional residual capacity, but peaked at moderate positive end-expiratory pressure after deflation from total lung capacity, further demonstrating the effects of volume history and providing experimental validation of the recruitment models of Hickling (AJRCCM 2001;163:69-78). These results support the interpretation of Pflex as pressure threshold for recruitment, but otherwise do not suggest a role for the pressure-volume curve in predicting steady-state lung volume.
Descriptors: respiratory system, respiration, acute lung injury, respiratory system disease, diagnosis, therapy, computed tomography, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, mechanical ventilation, therapeutic and prophylactic techniques, positive end expiratory pressure, pressure volume curve.

Ednick, M.D., M. Pagala, J.P. Barakat, G. Nino, P. Shah, J.N.J. Cunningham, M. Vaynblat, and M. Kazachkov (2007). Telemetric recording of intrapleural pressure. Journal of Surgical Research 138(1): 10-4. ISSN: 0022-4804.
Abstract: BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders.
Descriptors: exhalation physiology, inhalation physiology, manometry instrumentation, pleural cavity physiology, telemetry instrumentation, catheterization, consciousness, dogs, manometry methods, models, animal, motor activity, pressure, telemetry methods.

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.

Harris, S.B., M.G. Darwin, S.R. Russell, J.M. O'Farrell, M. Fletcher, and B. Wowk (2001). Rapid (0.5 degrees C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs. Resuscitation 50(2): 189-204. ISSN: 0300-9572.
Abstract: OBJECTIVE: Demonstrate minimally invasive rapid body core and brain cooling in a large animal model. DESIGN: Prospective controlled animal trial. SETTING: Private research laboratory. SUBJECTS: Adult dogs, anesthetized, mechanically ventilated. INTERVENTIONS: Cyclic lung lavage with FC-75 perfluorochemical (PFC) was administered through a dual-lumen endotracheal system in the new technique of 'gas/liquid ventilation' (GLV). In Trial-I, lavage volume (V-lav) was 19 ml/kg, infused and withdrawn over a cycle period (tc) of 37 s. (effective lavage rate V'-lav=31 ml/kg/min.) Five dogs received cold (approximately 4 degrees C) PFC; two controls received isothermic PFC. In Trial-II, five dogs received GLV at V-lav=8.8 ml/kg, tc=16 s, V'-lav=36 ml/kg/min. MEASUREMENTS AND MAIN RESULTS: Trial-I tympanic temperature change was -3.7+/-0.6 degrees C (SD) at 7.5 min, reaching -7.3+/-0.6 degrees C at 18 min. Heat transfer efficiency was 60%. In Trial-II, efficiency fell to 40%, but heat-exchange dead space (VDtherm) remained constant. Lung/blood thermal equilibration half-time was <8 s. Isothermic GLV caused hypercapnia unless gas ventilation was increased. At necropsy after euthanasia (24 h), modest lung injury was seen. CONCLUSIONS: GLV cooling times are comparable to those for cardiopulmonary bypass. Heat and CO(2) removal can be independently controlled by changing the mix of lavage and gas ventilation. Due to VDtherm of approximately 6 ml/kg in dogs, efficient V-lav is >18 ml/kg. GLV cooling power appears more limited by PFC flows than lavage residence times. Concurrent gas ventilation may mitigate heat-diffusion limitations in liquid breathing, perhaps via bubble-induced turbulence.
Descriptors: animal model, minimally invasive, rapid body core, brain cooling, hypothermia .

Hirota, K., Y. Hashimoto, T. Sato, H. Yoshioka, T. Kudo, A. Matsuki, and D.G. Lambert (2001). Bronchoconstrictive and relaxant effects of lidocaine on the airway in dogs. Critical Care Medicine. 29(5): 1040-4. ISSN: 0090-3493.
Abstract: OBJECTIVE: Intravenous lidocaine commonly is used to treat ventricular arrhythmias and to attenuate reflex airway constriction and intracranial pressure elevation during airway manipulation in intensive care units. There is much controversy as to the actions of lidocaine on the airway, so the aim of this study was to compare, in detail, the actions of lidocaine with those of bupivacaine and procaine on airway caliber and the associated changes in plasma catecholamine concentrations in the dog. DESIGN: Prospective, randomized, controlled experimental in vivo and in vitro study. SETTING: A university research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: In the first experiment, we evaluated the effects of intravenous local anesthetics--lidocaine 0-10 mg/kg (n = 7), bupivacaine 0-2.5 mg/kg (n = 7), or procaine 0-20 mg/kg (n = 7)--on basal airway tone. In second experiment, histamine (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 6), serotonin (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 7), and methacholine (0.5 microg/kg + 300 microg x kg(-1) x hr(-1), n = 7) were infused to determine the effects of lidocaine (0-10 mg/kg) on agonist-induced bronchoconstriction. In addition, the actions of lidocaine on vagal nerve stimulation were examined (n = 7). MEASUREMENTS AND MAIN RESULTS: Bronchial cross-sectional area at the third bronchial bifurcation of dogs was monitored continuously through a fiberoptic bronchoscope. In the first experiment, all local anesthetics produced a dose-dependent decrease in basal bronchial cross-sectional area. In the second experiment, lidocaine significantly potentiated histamine and serotonin-induced bronchoconstriction. In contrast, lidocaine antagonized methacholine- and vagal nerve stimulation-induced bronchoconstriction. CONCLUSION: We have clearly demonstrated that lidocaine may produce direct bronchoconstriction and worsen some agonist-induced bronchoconstriction, but it prevents reflex airway constriction. Therefore, we suggest that this agent be used with caution in asthmatics.
Descriptors: animal model, mongrel dogs, intravenous lidocaine, ventricular arrhythmias, reflex airway constriction, intracranial pressure elevation.

Hirota, K., S. Kabara, E. Hashiba, Y. Hashimoto, and A. Matsuki (2002). Apnea induces bronchoconstriction by vagally mediated reflexes in dogs. 2000 Annual Meeting of the American Society of Anesthesiologists, San Francisco, CA, USA; October 16-18, 2000,
Online: http://www.asa-abstracts.com
Abstract: Introduction: Hypoxia and hypecarbia modulate airway smooth muscle tone1. In addition, respiratory rhythms also change airway tone via pulmonary stretch receptor2. In this study, we determined effect of apnea on bronchial tone in dogs using our bronchoscopic method3. Methods: After approval of our University Animal Care Committee, 14 mongrel dogs anesthetized with pentobarbital (30 mg/kg iv + 2 mg/kg/hr) and pancuronium (0.2 mg/kg/hr) were assigned to two groups: control group (without vagotomy, group C, n=7) and vagotomy group (group V, n=7). The trachea was intubated with an endotracheal tube (ID 7 mm) that has a 2nd lumen for insertion of a superfine fiberoptic bronchoscope (OD 2.2 mm) to monitor the bronchial cross-sectional area (BCA) continuously as previously reported3. The BCA was measured with MacScope 2.56. In both groups, a respirator was turned off for 5 min to produce apnea. The BCA, arterial oxygen (PaO2) and carbon dioxide tensions (PaCO2) was assessed at before and 1, 2, 3, 4, and 5 min after respirator was tuned off. Changes in BCA are expressed as % of the basal. All data are mean(SEM). Statistical analysis were done by unpaired t-test and repeated measures ANOVA followed by Fisher's PLSD, appropriately. A p<0.05 was considered significant. Results: The BCA in group C time-dependently decreased to 99.4(1.1), 88.9(3.8)*, 79.5(4.5)**, 65.2(6.1)** and 57.6(4.7)** at 1, 2, 3, 4 and 5 min after apnea started, respectively, while did not in group V (*: p<0.05, **: p<0.01 vs group V). Apnea significantly decreased PaO2: 472(17), 445(8), 370(29)**, 282(37)**, 196(43)** and 149(43)**, and increased PaCO2: 41(1), 53(1)**, 58(2)**, 63(2)**, 67(2)** and 71(2)** before and 1, 2, 3, 4 and 5 min after apnea started (N.S between groups). Conclusion: The present study shows that apnea produces bronchoconstriction. In addition, this airway constriction is vagally mediated.
Descriptors: respiratory system, respiration, apnea, respiratory system disease, macscope 2.56, medical equipment, bronchoscopy, experimental surgical techniques, laboratory techniques, endotracheal tube, medical equipment, superfine fiberoptic bronchoscope, medical equipment, vagotomy, experimental surgical techniques, bronchial cross sectional area [bca], bronchial tone, bronchoconstriction, vagally mediated reflexes.

Hsia, C.C.W., R.L.J. Johnson, E.Y. Wu, A.S. Estrera, H. Wagner, and P.D. Wagner (2003). Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation-perfusion matching. Journal of Applied Physiology 95(4): 1370-1378. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Abstract: After pneumonectomy (Pnx), mechanical strain on the remaining lung is an important signal for adaptation. To examine how mechanical lung strain alters gas exchange adaptation after Pnx, we replaced the right lung of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was kept 1) inflated (Inf) to reduce mechanical strain of the remaining lung and maintain the mediastinum in the midline, or 2) deflated (Def) to allow lung strain and mediastinal shift. Gas exchange was studied 4-7 mo later at rest and during treadmill exercise by the multiple inert gas elimination technique while animals breathed 21 and 14% O2 in balanced order. In the Inf group compared with Def group during hypoxic exercise, arterial O2 saturation was lower and alveolar-arterial O2 tension difference higher, whereas O2 diffusing capacity was lower at any given cardiac output. Dispersion of the perfusion distribution was similar between groups at rest and during exercise. Dispersion of the ventilation distribution was lower in the Inf group at rest, associated with a much higher respiratory rate, but rose to similar levels in both groups during hypoxic exercise. Mean pulmonary arterial pressure at a given cardiac output was higher in the Inf group, whereas peak cardiac output was similar between groups. Thus creating lung strain by post-Pnx mediastinal shift primarily enhances diffusive gas exchange with only minor effects on ventilation-perfusion matching, consistent with the generation of additional alveolar-capillary surfaces but not conducting airways and blood vessels.
Descriptors: equipment apparatus devices and instrumentation, respiratory system, pneumonectomy, experimental surgical techniques, laboratory techniques, silicone prosthesis, prosthetic, alveolar arterial oxygen tension difference, arterial oxygen saturation, cardiac output, gas exchange adaptation, hypoxic exercise, mean pulmonary arterial pressure, oxygen diffusing capacity, respiratory rate.

Hubloue, I., D. Biarent, S. Abdel Kafi, G. Bejjani, C. Melot, R. Naeije, and M. Leeman (2003). Endothelin receptor blockade in canine oleic acid-induced lung injury. Intensive Care Medicine 29(6): 1003-6. ISSN: 0342-4642.
Abstract: OBJECTIVE: To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury. DESIGN: Prospective experimental study in dogs. SETTING: Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs. INTERVENTIONS: Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass. MEASUREMENTS AND RESULTS: Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmonary shunt. Treatment of established oleic acid lung injury with bosentan had no effect. CONCLUSIONS: Pretreatment, but not treatment, with bosentan, in the dose used, blunted the oleic acid-induced increase in pulmonary vascular resistance, suggesting that endothelins contribute to the increase in pulmonary vascular tone in the early stages of oleic acid lung injury.
Descriptors: animal model, lung injury, besentan, oleic acid, pulmonary vascular resistance, endothelins.

Hwang, J.H., Y.S. Kwon, E.H. Kang, W.J. Koh, K.W. Kang, H.C. Kim, M.P. Chung, H. Kim, O.J. Kwon, and G.Y. Suh (2004). Prone positioning improves oxygenation without adverse hemodynamic effects during partial liquid ventilation in a canine model of acute lung injury. Korean Journal of Internal Medicine 19(4): 237-242. ISSN: 1226-3303.
Abstract: Background : Partial liquid ventilation (PLV) and prone positioning can improve the arterial oxygenation (PaO2) in acute lung injury (ALI). We evaluated the effect of prolonged prone positioning during partial liquid ventilation (PLV) in a canine model of acute lung injury. Methods : Six mongrel dogs (weighing 17.4+/-0.7 kg each) were anesthetized, intubated and mechanically ventilated. After 1 hour of baseline stabilization, the dogs' lungs were instilled with 40 mL/kg perfluorocarbon (PFC). PLV was first performed in the supine position for 1 hour (S1), then in the prone position for 3 hours with hourly measurements (P1, P2, P3), and finally, PLV was performed with the animal turned back to the supine position for 1 hour (S2). Results : After instillation of the PFC, the PaO2 significantly increased from 99.2 +/- 32.6 mmHg at baseline to 198.1 +/- 59.2 mmHg at S1 (p=0.001). When the dogs were turned to the prone position, the PaO2 further increased to 288.3 +/- 80.9 mmHg at P1 (p=0.008 vs. S1): this increase was maintained for 3 hours, but the PaO2 decreased to 129.4 +/- 62.5 mmHg at S2 (p0.001 vs. P3). Similar changes were seen in the shunt fraction. There were no significant differences for the systemic hemodynamic parameters between the prone and supine positions. Conclusion : Prolonged prone positioning during PLV in an animal model of ALI appears to improve oxygenation without any hemodynamic compromise.
Descriptors: methods and techniques, respiratory system, respiration, acute lung injury, respiratory system disease, therapy, partial liquid ventilation, clinical techniques, therapeutic and prophylactic techniques, prone positioning, oxygenation .

Jahan Parwar, B., D.K. Chhetri, S. Hart, S. Bhuta, and G.S. Berke (2003). Development of a canine model for recurrent respiratory papillomatosis. Annals of Otology Rhinology and Laryngology 112(12): 1011-1013. ISSN: 0003-4894.
Abstract: A canine model for recurrent respiratory papillomatosis (RRP) was developed with canine oral papillomavirus (COPV) inoculated into the buccal mucosa and supraglottic larynx of 5 beagles. The animals received systemic immunosuppression with daily oral prednisone at doses of 0, 1, 2, 3, and 4 mg/kg. Buccal papillomata developed at 6 weeks in all animals and regressed by 10 weeks in the animals that received 0 and 1 mg/kg. The other animals had continuous growth of their buccal papillomata for 26 weeks. The animal that received 2 mg/kg developed papillomata on the lingual surface of the epiglottis that continued to grow through 26 weeks. Systemic oral prednisone successfully maintained COPV-induced oral and laryngeal papillomata in beagles. Thus, COPV-induced oral and laryngeal papillomata that are prednisone-maintained may have utility as a model for RRP.
Descriptors: oncology, human medicine, medical sciences, otolaryngology, human medicine, medical sciences, pulmonary medicine, human medicine, medical sciences, recurrent respiratory papillomatosis, neoplastic disease, respiratory system disease.

Kafi, S.A., P. Scillia, C. Melot, P.A. Gevenois, A. Pagnamenta, and R. Naeije (2002). Abnormal pulmonary vascular tone in canine oleic acid lung injury. Critical Care Medicine. 30(7): 1565-9. ISSN: 0090-3493.
Abstract: OBJECTIVE: To characterize the endothelium-dependent and endothelium-independent components of abnormal pulmonary vascular tone in canine oleic acid lung injury. DESIGN: Prospective, interventional study. SETTING: University laboratory. SUBJECTS: Twenty anesthetized mongrel dogs. INTERVENTIONS: Right heart catheterization was performed to measure pulmonary vascular resistance before and after induction of oleic acid lung injury in ten anesthetized and ventilated dogs. Pulmonary and internal mammary artery rings were sampled in these ten dogs with oleic acid injury and in ten anesthetized healthy control dogs. We also studied the responses to acetylcholine, to phenylephrine, and to hypoxia of the intact or endothelium-denuded rings mounted in organ baths. MEASUREMENTS AND MAIN RESULTS: Oleic acid lung injury was associated with an increase in pulmonary vascular resistance from 118 +/- 11 to 245 +/- 47 dyne.sec.cm-5.m-2 and a decrease in the Pao2/Fio2 ratio from 451 +/- 42 to 139 +/- 26 mm Hg (mean +/- se, p <.05 and p <.01, respectively). Acetylcholine-induced relaxation was decreased in the oleic acid pulmonary artery rings compared with the controls (85 +/- 3% vs. 99 +/- 6% of precontraction level, p <.05). Phenylephrine-induced contraction was decreased in denuded oleic acid pulmonary artery rings compared with the controls (81 +/- 8% vs. 102 +/- 10% of contraction to KCl 120 mM, p <.05). In vitro hypoxia induced a small endothelium-dependent contraction followed by an endothelium-independent relaxation. These responses were not different in oleic acid lung artery rings and in controls, except for a decrease in hypoxic contraction in the oleic acid pulmonary artery rings. In vitro hypoxic pulmonary vasoconstriction and relaxation were, respectively, directly (r =.48) and inversely (r = -.67) correlated with oleic acid-induced increase in pulmonary vascular resistance. There was no correlation between in vitro internal mammary artery reactivity and oleic acid-induced increase in pulmonary vascular resistance. CONCLUSIONS: Oleic acid-induced lung injury slightly impairs pulmonary arterial endothelium-dependent relaxation and endothelium-independent contraction. In vitro hypoxic pulmonary vasoreactivity is related to in vivo oleic acid-induced increase in pulmonary vascular resistance.
Descriptors: animal model, oleic acid, induced lung injury, pulmonary vasoreactivity.

Katzenelson, R., A. Perel, H. Berkenstadt, S. Preisman, S. Kogan, L. Sternik, and E. Segal (2004). Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water. Critical Care Medicine. 32(7): 1150-4. ISSN: 0090-3493.
Abstract: OBJECTIVE: Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema. DESIGN: Prospective, randomized animal study. SETTING: A university animal research laboratory. SUBJECTS: Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg. INTERVENTIONS: The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique. MEASUREMENTS AND MAIN RESULTS: There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement. CONCLUSIONS: Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.
Descriptors: animal model, induced edema, pulmonary edema, thermodilution measuremnt .

Khosla, S., S. Muruguppan, E. Gutmark, and R. Scherer (2007). Vortical flow field during phonation in an excised canine larynx model. Annals of Otology, Rhinology, and Laryngology 116(3): 217-28. ISSN: 0003-4894.
Abstract: OBJECTIVES: To more fully understand the mechanisms of vocal fold vibration and sound production, we studied the velocity flow fields above the folds. Such velocity fields during phonation have not been reported in the literature. METHODS: Using the particle image velocimetry method for 3 excised canine larynges, we obtained the velocity fields in the mid-membranous coronal plane during different phases of phonation. The velocity field was determined synchronously with the vocal fold motion recorded by high-speed videography. RESULTS: The results show that vortices occur immediately above the vocal folds and that the location and shape of the vortices depend on the phase of the phonation cycle. Consistent vortical structures found included starting vortices, Kelvin-Helmholtz vortices, entrainment vortices, and vortices directly above the folds during the divergent glottal stage. CONCLUSIONS: These vortical structures were consistently found during specific phases of the glottal cycle for 3 canine larynges that significantly varied in size. This consistent behavior suggests that the vortices may be important for both vibration and sound production; however, further study is needed to prove this. The clinical significance of these vortices is discussed.
Descriptors: acoustics, larynx physiology, phonation physiology, dogs, lasers, models, animal, photography, signal processing, computer assisted.

Kling, D.E. and J.J. Schnitzer (2007). Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital diaphragmatic hernia (CDH). American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 145c(2): 139-57. ISSN: 1552-4868.
Abstract: Congenital diaphragmatic hernia (CDH) is a congenital malformation that occurs with a frequency of 0.08 to 0.45 per 1,000 births. Children with CDH are born with the abdominal contents herniated through the diaphragm and exhibit an associated pulmonary hypoplasia which is frequently accompanied by severe morbidity and mortality. Although the etiology of CDH is largely unknown, considerable progress has been made in understanding its molecular mechanisms through the usage of genetic, teratogenic, and surgical models. The following review focuses on the teratogenic and surgical models of CDH and the possible molecular mechanisms of nitrofen (a diphenyl ether, formerly used as an herbicide) in both induction of CDH and pulmonary hypoplasia. In addition, the mechanisms of other compounds including several anti-inflammatory agents that have been linked to CDH will be discussed. Furthermore, this review will also explore the importance of vitamin A in lung and diaphragm development and the possible mechanisms of teratogen interference in vitamin A homeostasis. Continued exploration of these models will bring forth a clearer understanding of CDH and its molecular underpinnings, which will ultimately facilitate development of therapeutic strategies. (c) 2007 Wiley-Liss, Inc.
Descriptors: diaphragm embryology, hernia, diaphragmatic embryology, lung embryology, vitamin a physiology, vitamin a deficiency complications, disease models, animal, dogs, hernia, diaphragmatic chemically induced, hernia, diaphragmatic genetics, models, animal, phenyl ethers pharmacology, rabbits, rats, sheep, signal transduction, species specificity, teratogens pharmacology, tretinoin metabolism, vitamin a metabolism.

Krolo, M., A.G. Stucke, E.A.E. Stuth, F.A. Hopp, and E.J. Zuperku (2003). Responses of prebotzinger complex respiratory neurons to pulmonary afferent inputs in the decerebrate canine model. FASEB Journal 17(4-5): Abstract No. 303.10. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: nervous system, neural coordination, respiratory system, respiration, cycle triggered histograms, histology and cytology techniques, laboratory techniques, decerebration, experimental surgical techniques, extracellular single unit recording, phrenic neurogram, electrically induced step vagal input patterns.

Kwon, O.J., G.Y. Suh, M.P. Chung, J. Kim, J. Han, and H. Kim (2003). Tracheal stenosis depends on the extent of cartilaginous injury in experimental canine model. Experimental Lung Research 29(6): 329-338. ISSN: 0190-2148.
Abstract: To test the hypothesis that the development of tracheal stenosis would depend on the extent of tracheal cartilaginous injury, either 90degree (n=6) or 180degree (n=6) of anterior wall of 4 tracheal rings were cauterized in 12 mongrel dogs using Nd-YAG laser. Beginning at 3 weeks after cauterization, 180degree tracheal injury resulted in life-threatening tracheal stenosis whereas 90degree injury did not. Gross and microscopic examinations showed that after 180degree injury, tracheal stenosis was accompanied by the loss of tracheal cartilage and dense fibrosis. These results indicate that tracheal stenosis depends on the extent of tracheal injury in experimental canine model.
Descriptors: respiratory system, respiration, tracheal cartilaginous injury, connective tissue disease, tracheal stenosis, respiratory system disease, nd yag laser, neodymium yag laser, laboratory equipment, microscopic examination, imaging and microscopy techniques, laboratory techniques.

Lafrentz, J.R., S.E. Brietzke, and E.A. Mair (2003). Evaluation of palatal snoring surgery in an animal model. Otolaryngology Head and Neck Surgery 129(4): 343-52. ISSN: 0194-5998.
Abstract: OBJECTIVE: We introduce an animal model to reproduce and measure palatal snoring and to assess the effectiveness of cautery-assisted palatal stiffening operation and injection snoreplasty versus a control (no palatal intervention) on treatment of palatal flutter snoring.Study design and setting An anesthetized laboratory canine model uses 2 simultaneous temporary tracheotomies. An inferior tracheotomy is cannulated with an endotracheal tube for ventilation. A superior tracheotomy is cannulated with a tube passed cephalad and seated in the hypopharynx. Negative pressure applied to the upper tube leads to partial collapse of the upper airway with palatal fluttering, and the anesthetized dog snores. Videostroboscopy records palatal flutter frequency before and after surgical intervention. Preoperative and postoperative palatal assessments are made on 15 beagles. RESULTS: Cautery-assisted palatal stiffening operation and injection snoreplasty objectively stiffen the canine soft palate with diminished snoring compared with controls.Conclusion and significance We provide a reproducible animal model to experimentally measure new interventions to treat palatal flutter snoring.
Descriptors: animal model, snoring, intervention, palatal stiffening operation, injection snoreplasty.

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.

Leduc, D., E. Brunko, and A. de Troyer (2001). Response of the canine internal intercostal muscles to chest wall vibration. American Journal of Respiratory and Critical Care Medicine 163(1): 49-54. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: Although high-frequency mechanical vibration of the rib cage reduces dyspnea, its effects on the respiratory muscles are largely unknown. We have previously shown that in anesthetized dogs, vibrating the rib cage during inspiration elicits a marked increase in the inspiratory electromyographic (EMG) activity recorded from the external intercostal muscles but does not affect tidal volume (VT). In the present studies, we have tested the hypothesis that the maintenance of VT results from the concomitant contraction of the internal interosseous (expiratory) intercostals. When the rib cage was vibrated (40 Hz) during hyperventilation-induced apnea, a prominent activity was recorded from the external intercostals but no activity was recorded from the internal intercostals, including when the muscles were lengthened by passive inflation. The internal intercostals remained also silent when vibration was applied during spontaneous inspiration, and the phasic expiratory EMG activity recorded from them was unaltered when vibration was applied during expiration. Thus, the internal interosseous intercostals in dogs are much less sensitive to vibration than the external intercostals, and they do not interfere with the action of these latter during rib cage vibration. This lack of sensitivity might be the result of a reflex inhibition of the muscle spindle afferents by afferents from external intercostal muscle spindles.
Descriptors: mechanical vibration, rib cage, dyspnea, EMG, passive inflation.

Leduc, D. and A. de Troyer (2003). Mechanical effect of muscle spindles in the canine external intercostal muscles. Journal of Physiology 548(Pt 1): 297-305. ISSN: 0022-3751.
NAL Call Number: 447.8 J82
Abstract: High-frequency mechanical vibration of the ribcage increases afferent activity from external intercostal muscle spindles, but the effect of this procedure on the mechanical behaviour of the respiratory system is unknown. In the present study, we have measured the changes in external intercostal muscle length and the craniocaudal displacement of the ribs during ribcage vibration (40 Hz) in anaesthetized dogs. With vibration, external intercostal inspiratory activity increased by approximately 50 %, but the respiratory changes in muscle length and rib displacement were unaltered. A similar response was obtained after the muscles in the caudal segments of the ribcage were sectioned and the caudally oriented force exerted by these muscles on the rib was removed, thus suggesting that activation of external intercostal muscle spindles by vibration generates little tension. Prompted by this observation, we also examined the role played by the external intercostal muscle spindles in determining the respiratory displacement of the ribs during breathing against high inspiratory airflow resistances. Although resistances consistently elicited prominent reflex increases in external intercostal inspiratory activity, the normal inspiratory cranial displacement of the ribs was reversed into an inspiratory caudal displacement. Also, this caudal rib displacement was essentially unchanged after section of the external intercostal muscles, whereas it was clearly enhanced after denervation of the parasternal intercostals. These findings indicate that stretch reflexes in external intercostal muscles confer insufficient tension on the muscles to significantly modify the mechanical behaviour of the respiratory system.
Descriptors: high frequency mechanical vibration, ribcage, intercostal muscle spindles, mechanical behavior, respiratory system.

Lim, C.M., S.S. Lee, J.S. Lee, Y. Koh, T.S. Shim, S.D. Lee, W.S. Kim, D.S. Kim, and W.D. Kim (2003). Morphometric effects of the recruitment maneuver on saline-lavaged canine lungs: a computed tomographic analysis. Anesthesiology (Hagerstown) 99(1): 71-80. ISSN: 0003-3022.
Abstract: Background: In the face of widespread use of lung-protective, low-volume ventilation in patients with acute lung injury, interest in the recruitment maneuver (RM) is growing. Little is known about lung-morphometric effects of the RM as compared with positive end-expiratory pressure (PEEP) titration (PT) without the RM. Methods: RM was defined as a stepwise change in PEEP from baseline to 10, 20, 30, and 20 cm H2O every 30 s, after which PEEP was reset at the lower inflection point + 2 cm H2O. For PT, PEEP was simply increased from baseline to the lower inflection point + 2 cm H2O. Both maneuvers were performed in 10 lung-lavaged dogs. Computed tomography of the lung was performed before and 30 s and 30 min after the maneuver. Results: Thirty seconds after the maneuver, the decrease in the amount of nonaerated plus poorly aerated lung was greater and decreases in Hounsfield units in the caudal and dorsal lung regions were greater with the RM than with the PT. The hyperaerated lung volume after the RM tended to be greater than that after the PT. At 30 s and 30 min after the maneuver, gas plus tissue volume, gas-only volume, and gas-tissue ratio of the lung were greater with the RM than with the PT. At both time points after the maneuver, the coefficient of variation of regional Hounsfield units, an index of regional heterogeneity of aeration, was lower with the RM than with the PT. Conclusions: Compared with PT, the RM resulted in a greater lung volume, better aeration of the most dependent lung, and less regional heterogeneity of aeration. However, the RM tended to induce a greater increase in hyperaerated lung volume than did the PT.
Descriptors: methods and techniques, respiratory system, respiration, computed tomographic analysis, computed tomography, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, positive end expiratory pressure titration, recruitment maneuver, clinical techniques, aeration, regional heterogeneity, gas plus tissue volume, gas only volume, gas tissue ratio, hyperaerated lung volume, morphometric effects, regional hounsfield units, coefficient of variation, saline lavaged.

Lin, V.W., I. Hsiao, X. Deng, Y.S. Lee, and S. Sasse (2004). Functional magnetic ventilation in dogs. Archives of Physical Medicine and Rehabilitation 85(9): 1493-8. ISSN: 0003-9993.
Abstract: OBJECTIVE: To investigate the efficacy of the magnetic stimulation of inspiratory muscles as an alternative to mechanical ventilation and functional electric stimulation. DESIGN: A prospective before-after trial. SETTING: Functional magnetic stimulation laboratory in a Veterans Administration health care system. ANIMALS: Six male mongrel dogs, each weighing between 25 and 35 kg. INTERVENTIONS: Commercially available magnetic stimulators with a round magnetic coil were used. The center of the magnetic coil was placed posteriorly over the C5-7 vertebrae of the spinal cord transected dogs. Magnetic stimulation parameters were set at 80% intensity, 20 Hz, and a 1.2-second on and 3.8-second off pulse train. MAIN OUTCOME MEASURES: The major outcomes were changes in tidal volume (VT), tracheal pressure (Ptr), and arterial partial pressure of carbon dioxide (PaCO2) and oxygen sustained by magnetic stimulation over time. RESULTS: The average Vt and Ptr produced during functional magnetic ventilation (FMV) were.47+/-.07 L and -4.7+/-.51 cmH2O, respectively. Blood gas data showed that PaCO2 increased from a baseline of 33 to 75 mmHg, whereas pH decreased from 7.33 to 6.99 at the end of the 1-hour FMV period. CONCLUSIONS: FMV was achieved for 2 hours in dogs with C2 spinal cord transection. Additional refinements in magnetic stimulation are needed to improve ventilation in animals.
Descriptors: animal model, mongrel dogs, spinal cord transection, magnetic stimulatior, alternatives, mechanical ventilation.

Loer, S.A., L.A. Schwarte, M.A. Pakulla, O. Picker, and T.W. Scheeren (2003). Partial liquid ventilation: effects of positive end-expiratory pressure on perfluorocarbon evaporation from the lungs of anesthetized dogs. Intensive Care Medicine 29(3): 467-70. ISSN: 0342-4642.
Abstract: OBJECTIVE: Perfluorocarbons are eliminated during partial liquid ventilation mainly by evaporation via the airways. We examined whether this is affected by the level of end-expiratory airway pressure. DESIGN AND SETTING: Observational cohort animal study in the animal laboratory of a university hospital. SUBJECTS: Five foxhound dogs. INTERVENTIONS: The anesthetized dogs underwent partial liquid ventilation (5 ml/kg perfluorocarbon) at constant respiratory rate (17+/-1 breaths/min) and tidal volume (10 ml/kg). The level of end-expiratory airway pressure was varied repeatedly between 0, 5, and 10 cmH(2)O every 25 min. MEASUREMENTS AND RESULTS: Expired gas was collected in reservoirs to determine evaporative perfluorocarbon loss gravimetrically. Any increase in end-expiratory airway pressure increased while any decrease in end-expiratory airway pressure reduced evaporative perfluorocarbon loss. Mean initial elimination at an end-expiratory airway pressure of 5 cmH(2)O was 19.6+/-3.8 microl/kg per minute; this decreased by 28% at an end-expiratory airway pressure of 0 cmH(2)O and increased by 46% at an end-expiratory airway pressure of 10 cmH(2)O. At equal levels of end-expiratory airway pressure evaporation decreased linearly over time. CONCLUSIONS: Our results suggest that the level of end
Descriptors: animal model, foxhound dogs, perfluorocarbons, partial liquid ventilation.

Mcverry, B.J., X. Peng, P.M. Hassoun, S. Sammani, B.A. Simon, and J.G.N. Garcia (2004). Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. American Journal of Respiratory and Critical Care Medicine 170(9): 987-993. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: Excessive mechanical stress is a key component of ventilator-associated lung injury, resulting in profound vascular leak and an intense inflammatory response. To extend our in vitro observations concerning the barrier-protective effects of the lipid growth factor sphingosine 1-phosphate (Sph 1-P), we assessed the ability of Sph 1-P to prevent regional pulmonary edema accumulation in clinically relevant rodent and canine models of acute lung injury induced by combined intrabronchial endotoxin administration and high tidal volume mechanical ventilation. Intravenously delivered Sph 1-P significantly attenuated both alveolar and vascular barrier dysfunction while significantly reducing shunt formation associated with lung injury. Whole lung computed tomographic image analysis demonstrated the capability of Sph 1-P to abrogate significantly the accumulation of extravascular lung water evoked by 6-hour exposure to endotoxin. Axial density profiles and vertical density gradients localized the Sph 1-P response to transitional zones between aerated and consolidated lung regions. Together, these results indicate that Sph 1-P represents a novel therapeutic intervention for the prevention of pulmonary edema related to inflammatory injury and increased vascular permeability.
Descriptors: pharmacology, respiratory system, respiration, lung injury, injury, respiratory system disease, pulmonary edema, respiratory system disease, drug therapy, pathology, prevention and control, mechanical ventilation, clinical techniques, therapeutic and prophylactic techniques, tomography, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, mechanical stress.

Miao, C.H., B. Sun, H. Jiang, Z.G. Xue, and R. Lindwall (2002). Pharmacodynamics and pharmacokinetics of inhaled nitric oxide in dogs with septic acute respiratory distress syndrome. Acta Pharmacologica Sinica 23(3): 278-84. ISSN: 1671-4083.
Abstract: AIM: To evaluate pharmacodynamics and pharmacokinetics of inhaled nitric oxide (iNO) in dogs with acute respiratory distress syndrome (ARDS). METHODS: ARDS, induced after iv injection of endotoxin, was evidenced by reduction of paO2/FiO2 from (62.5 +/- 2.8) to (26 +/- 4) kPa and dynamic lung compliance (Cdyn) from (14.8 +/- 0.7) to (8.6 +/- 0.6) mL.kPa-1 . kg-1, increase of dead space (VD/VT) from (0.14 +/- 0.06) to (0.58 +/- 0.05), intrapulmonary shunting (Qs/Qt) from 4.7 % +/- 1.7 % to 39 % +/- 7 %, and pulmonary vascular resistance index (PVRI) from (16 +/- 4) to (51 +/- 8) kPa.s.L-1 . m-2 (all P < 0.05), along with severe intrapulmonary neutrophil recruitment and peripheral neutropenia. The animals were then treated as either a control or an NO group (n = 6 each, iNO 0.4 - 3.2 micromol/L) for another 10 h. RESULTS: More survival was found in NO group (4/6 vs 0/6, P < 0.05). iNO at 0.8, 1.6, and 3.2 micromol/L (20, 40, and 80 ppm) resulted in > 40 % increase of paO2/FiO2 and Cdyn, a reduction of VD/VT to 0.32, Qs/Qt to < 25 %, and PVRI by > 50 % (30.8 kPa . s . L-1 . m-2) compared to the control. Optimal iNO dose was around 0.8 micromol/L as higher methemoglobin (MetHb, > 3 %) was found at higher NO. iNO had no adverse effects on surfactant phospholipids and lung fluid balance, but attenuated expression of tumor necrosis factor alpha,beta2 integrin CD11b, and interleukin-8 mRNA in the lungs by 22 %, 44 %, and 25 %, respectively (P < 0.05). CONCLUSION: Pharmacodynamics of iNO in this model was related to improvement in gas exchange, Cdyn, PVRI, and suppression of proinflammatory cytokine expression in the lungs, and its adverse effect was mainly confined to MetHb at higher NO dose.
Descriptors: pharmacodynamics, pharmacokinetics, inhaled nitric oxide (iNO), acute respiratory distress syndrome, intrapulmonary neutrophil recruitment, peripheral neutropenia, surfactant phospholipids, lung fluid balance.

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.

Nair, B. and A.R. Elmore (2003). Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite. International Journal of Toxicology 22(Supplement 2): 63-88. ISSN: 1091-5818.
NAL Call Number: RA1190.J61
Abstract: Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC50 of >400 mg/m3 in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m3 of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.
Descriptors: cosmetics, toxicology, pulmonary edema, respiratory system disease, oral dose animal toxicity test, laboratory techniques, genotoxicity data, lung capacity parameters, pH, skin penetration.

Ochs, M., H. Fehrenbach, and J. Richter (2004). Occurence of lipid bodies in canine type ii pneumocytes during hypothermic lung ischemia. Anatomical Record 277A(2): 287-297. ISSN: 0003-276X.
NAL Call Number: QL801 .A53
Descriptors: biochemistry and molecular biophysics, respiratory system, respiration, cardiac arrest, heart disease, hypothermic lung ischemia, respiratory system disease, vascular disease, pathology, energy filtering transmission, electron microscopy, imaging, microscopy techniques, laboratory techniques, stereology, laboratory techniques, alveolar epithelial regeneration.

Olmos Zuniga, J.R., C. Hernandez Jimenez, E. Diaz Martinez, R. Jasso Victoria, A. Sotres Vega, M.O. Gaxiola Gaxiola, J. Villalba Caloca, M. Baltazares Lipp, P. Santillan Doherty, and J.A. Santibanez Salgado (2007). Wound healing modulators in a tracheoplasty canine model. Journal of Investigative Surgery the Official Journal of the Academy of Surgical Research 20(6): 333-8. ISSN: 0894-1939.
Abstract: Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p < .05 and Tukey p < .01). Thus, hyaluronic acid or collagen polyvinylpyrrolidone administered after tracheal anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.
Descriptors: collagen pharmacology, hyaluronic acid pharmacology, povidone pharmacology, trachea surgery, wound healing drug effects, dogs, fibrosis, models, animal, postoperative complications etiology, trachea pathology, tracheal stenosis etiology.

Omori, K., T. Nakamura, S. Kanemaru, H. Kojima, A. Magrufov, Y. Hiratsuka, and Y. Shimizu (2004). Cricoid regeneration using in situ tissue engineering in canine larynx for the treatment of subglottic stenosis. Annals of Otology Rhinology and Laryngology 113(8): 623-627. ISSN: 0003-4894.
Abstract: The purpose of the present study was to evaluate the efficacy of cricoid regeneration via in situ tissue engineering in a canine larynx for the treatment of subglottic stenosis. As the tissue scaffold, a Marlex mesh tube coated by collagen sponge was used for a rigid airway framework and for tissue regrowth around the tube. On 5 dogs, the larynx was exposed and the anterior third of the cricoid cartilage was resected. The tube was anastomosed to the lower edge of the thyroid cartilage and to the first tracheal cartilage. By postoperative endoscopic examination at 3 to 7 months, no airway obstruction was observed in any of the dogs. There was granulation tissue in 2 dogs and slight mesh exposure in I dog, but they were asymptomatic. Confluent regeneration of the epithelium over the scaffold and good incorporation of the scaffold mesh into the host tissue were observed after surgery.
Descriptors: bioprocess engineering, respiratory system, respiration, subglottic stenosis, respiratory system disease, diagnosis, therapy, endoscopy, diagnostic techniques, laboratory techniques.

Pagnamenta, A., P. Fesler, A. Vandinivit, S. Brimioulle, and R. Naeije (2003). Pulmonary vascular effects of dobutamine in experimental pulmonary hypertension. Critical Care Medicine. 31(4): 1140-6. ISSN: 0090-3493.
Abstract: OBJECTIVE: To characterize the dose-related effects of dobutamine on pulmonary vascular tone and associated changes in right ventricular afterload in canine microembolic lung injury .DESIGN: Prospective, interventional study. SETTING: University laboratory. SUBJECTS: Ten anesthetized and ventilated dogs. INTERVENTIONS: Right heart catheterization for the measurement of pulmonary vascular resistance by multipoint mean pulmonary artery pressure (Ppa)/cardiac output (Q) plots, partitioning of pulmonary vascular resistance by the occlusion method, and determination of pulmonary arterial input impedance from spectral analysis of Ppa and Q waves, in ten anesthetized and ventilated dogs, before and after induction of acute microembolic lung injury, and without or with 5, 10, 15, and 20 microg.kg(-1).min(-1) dobutamine. MEASUREMENTS AND MAIN RESULTS: Microembolic pulmonary hypertension was associated with a shift of Ppa/Q plots to higher pressures, a slight decrease in the arterial component of pulmonary vascular resistance, a decrease in characteristic impedance, and an increase in the pulsatile component of right ventricular hydraulic load. At baseline, dobutamine had no effect on Ppa/Q plots at 5 and 10 microg.kg(-1).min(-1) but increased Ppa at 15 and 20 microg.kg(-1).min(-1). In microembolic pulmonary hypertension, the only effect of dobutamine on Ppa/Q plots was a decrease in Ppa at 20 microg.kg(-1).min(-1). Dobutamine had no effect on the partitioning of pulmonary vascular resistance or on pulmonary arterial input impedance spectrum. CONCLUSIONS: Dobutamine at doses up to 10 microg.kg(-1).min(-1) has no flow-independent effect on the normal or the acutely hypertensive pulmonary circulation. Higher doses may be constricting or dilating depending on preexisting tone.
Descriptors: lung injury, animal model, ventilated dogs, dose-related effects, dobutamine, pulmonary vascular tone, pulmonary artery pressure.

Park, C.K., K.S. Park, S.H. Jheon, K.Y. Kwon, Y.J. Jeon, and H.C. Kim (2003). Lung preservation study by canine sequential bilateral single lung transplantation model. Transplantation Proceedings 35(1): 453-455. ISSN: 0041-1345.
NAL Call Number: RD120.7.T68
Descriptors: methods and techniques, respiratory system, respiration, lung edema, respiratory system disease, bilateral single lung transplantation, clinical techniques, therapeutic and prophylactic techniques, arterial oxygen tension, lung preservation study, pulmonary arterial pressure, pulmonary vascular resistance, total ischemic time.

Pellett, A.A., K.C. Lord, M.S. Champagne, B.P. deBoisblanc, R.W. Johnson, and M.G. Levitzky (2002). Pulmonary capillary pressure during acute lung injury in dogs. Critical Care Medicine 30(2): 403-9. ISSN: 0090-3493.
Abstract: OBJECTIVES: To measure pulmonary capillary pressure and pulmonary artery occlusion pressures both during control conditions and during acute lung injury and to evaluate the effects of inotropic therapy and volume loading on these measurements after lung injury. DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eighteen heartworm-free mongrel dogs. INTERVENTIONS: Dogs were anesthetized (sodium pentobarbital, 30 mg/kg intravenously), intubated, and mechanically ventilated. A femoral artery and vein and the right external jugular vein were cannulated. After a median sternotomy, two pulmonary artery catheters were inserted via the jugular vein into the left and right lower lobar pulmonary arteries. Oleic acid (0.03 mL/kg) was administered to all dogs via the left pulmonary artery catheter, whereas the right lower lobe served as control. A baseline group of dogs received no further interventions, whereas two additional groups were given dobutamine (30-60 microg x kg(-1) x min(-1)intravenously) or saline boluses (1-2 L) before measurements were obtained after oleic acid lung injury. MEASUREMENTS AND MAIN RESULTS: Capillary pressure was estimated in both lower lung lobes by using the pulmonary artery occlusion method. Pulmonary capillary and pulmonary artery occlusion pressures were measured before and 2 hrs after oleic acid administration. Left lower lobar capillary pressure increased in all three groups, as did the difference between capillary pressure and pulmonary artery occlusion pressure. Capillary pressure in the control right lower lobe increased significantly only in the saline-loaded dogs, whereas the difference between the right-sided capillary and occlusion pressures increased only in the dogs given dobutamine. CONCLUSIONS: Oleic acid lung injury increases pulmonary capillary pressure independent of pulmonary artery occlusion pressure. The gradient between the two pressures was not significantly affected by volume loading or dobutamine infusion.
Descriptors: animal model, lung injury, pulmonary capillary pressure, pulmonary artery occlusion pressures, volume loading, dobutamine infusion.

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, M., P.R. Eastwood, C.A. Smith, and J.A. Dempsey (2001). Nonchemical elimination of inspiratory motor output via mechanical ventilation in sleep. American Journal of Respiratory and Critical Care Medicine 163(6): 1356-64. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: In six dogs studied in nonrapid eye movement (NREM) sleep, we found that the frequency, volume, and timing of application of mechanical ventilator breaths had marked and sustained inhibitory effects on diaphragm electromyogram (EMG(di)). Single ventilator breaths of tidal volume (VT) 75-200% of control caused apnea (up to three times eupneic expiratory time [TE]) when applied during the initial 25-65% of expiratory time. When continuous controlled mechanical ventilation (CMV) was applied with ventilator frequency increased as little as 1 cycle/min > eupnea and Pa(CO(2)) and VT maintained at near eupneic control levels, EMG(di) was silenced and triangularis sterni EMG (EMG(ts)) became tonic within 2 to 5 ventilator cycles. On cessation of normocapnic CMV, apnea ensued with TE ranging from 1.2 to five times eupneic TE. The spontaneous VT and EMG(di) determined immediately after these prolonged apneas were also markedly reduced in amplitude. The larger the VT applied during the isocapnic CMV (120-200% of eupnea) and the longer the duration of the CMV (3-90 s), the longer the duration of the postventilator apnea. Significant postventilator apneas and postapneic hypoventilation also occurred even when end-tidal CO(2) pressure (PET(CO(2))) was raised 3-5 mm Hg > eupnea (and 7-10 mm Hg > normal apneic threshold) throughout CMV trials at raised frequency and VT. Our findings demonstrate that the increased frequency of CMV was critical to the elimination of inspiratory motor output and the onset of tonic expiratory muscle activity; furthermore, once EMG(di) was silenced, the tidal volume and duration of the passive mechanical ventilation determined the magnitude of the short-term inhibition of inspiratory motor output after cessation of CMV.
Descriptors: nonrapid eye movement (NREM) sleep, mechanical ventilator breaths, diaphragm electromyogram, ventilator breaths .

Schweitzer, C.E., J.L. Johnson, S.G. Vincent, and J.T. Fisher (2003). Static and dynamic behavior of neonatal canine slowly adapting receptors. FASEB Journal 17(4-5): Abstract No. 558.2. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: cell biology, development, respiratory system, respiration, breathing control, neonates, transpulmonary pressure.

Suga, K., Y. Yuan, N. Ogasawara, T. Tsukuda, and N. Matsunaga (2003). Altered clearance of gadolinium diethylenetriaminepentaacetic acid aerosol from bleomycin-injured dog lungs: initial observations. American Journal of Respiratory and Critical Care Medicine 167(12): 1704-1710. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: To characterize altered alveolar transfer to solute in bleomycin (BLM)-injured lungs, eight dogs underwent a gadolinium diethylenetriaminepentaacetic acid aerosol (Gd-AS) magnetic resonance imaging study before and on Days 7 and 40 after tracheal instillation of BLM (0.75 mg) in the left lungs. Consecutive fast-gradient echo magnetic resonance imaging was acquired during and after spontaneous inhalation of 200-mM Gd-AS. The slope (Kep) and clearance half-time (T1/2) of logarithmic regression lines for clearance curves were estimated. Histology on Day 40 was compared with that on Day 7 in another three dogs. On Days 7 and 40, Gd-AS deposition was heterogeneously reduced in the affected lungs. On Day 7 with multifocal intraalveolar exudative changes, Kep in affected areas was significantly increased compared with baseline (2.5X10-3 minutes-1+-0.3 versus 1.7X10-3 minutes-1+-0.2, p<0.0001), with significant decrease in T1/2 (121.6+-19.7 minutes vs. 170.4+-15.8 minutes, p<0.001). However, on Day 40 with multifocal interstitial fibrosis, Kep and T1/2 were recovered toward baseline. BLM-injured lungs can be characterized by accelerated Gd-AS clearance during the acute exudative phase and their recovery during the chronic fibrotic phase. This technique is acceptable for monitoring alveolar transfer changes in BLM-injured lungs.
Descriptors: biochemistry and molecular biophysics, respiratory system, respiration, lung injury, injury, respiratory system disease, magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, initial observations.

Sugita, M., P. Ferraro, A. Dagenais, M.E. Clermont, P. Barbry, R.P. Michel, and Y. Berthiaume (2003). Alveolar liquid clearance and sodium channel expression are decreased in transplanted canine lungs. American Journal of Respiratory and Critical Care Medicine 167(10): 1440-1450. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: To determine the impact of transplantation-associated injury on the clearance mechanisms of pulmonary edema, we created a canine single lung transplant model. After 3 hours of preservation and 4 hours of reperfusion, right native lungs and left transplanted lungs were used to measure alveolar liquid clearance (ALC) in ex vivo liquid-filled lung preparations. We also examined the role of the pulmonary circulation in edema clearance in in vivo liquid-filled lungs between 4 and 8 hours of reperfusion. To study molecular modifications in ALC, we also measured expression levels of the epithelial sodium channel (ENaC) and sodium-potassium-adenosine triphosphatase (ATPase). We found that ALC was significantly lower in transplanted than in right native lungs ex vivo (p<0.05) and that transplanted lungs did not respond to the beta-adrenergic agonist terbutaline. Our in vivo study confirmed the ex vivo results. Molecular analyses revealed that ENaC messenger RNA but not sodium-potassium-ATPase was significantly decreased in transplanted lungs (p<0.01). Furthermore, there was a significant decrease in ENaC protein expression. Therefore, we conclude that the current investigation indicates that the lung injury caused by lung preservation and transplantation significantly reduces the edema clearance ability of transplanted lungs.
Descriptors: biochemistry and molecular biophysics, respiratory system, respiration, veterinary medicine, medical sciences, ischemia reperfusion injury, vascular disease, pulmonary edema, respiratory system disease, lung transplantation, clinical techniques, therapeutic and prophylactic techniques, molecular analyses, genetic techniques, laboratory techniques.

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 .

Vassalli, F., S. Pierre, V. Julien, Y. Bouckaert, S. Brimioulle, and R. Naeije (2001). Inhibition of hypoxic pulmonary vasoconstriction by carbon monoxide in dogs. Critical Care Medicine. 29(2): 359-66. ISSN: 0090-3493.
Abstract: OBJECTIVE: We tested the hypothesis that carbon monoxide might participate in the modulation of hypoxic pulmonary vasoconstriction (HPV) by prostacyclin (PGI2) and nitric oxide. DESIGN: Prospective, interventional study. SETTING: University laboratory. SUBJECTS: Nineteen intact anesthetized mongrel dogs. INTERVENTIONS: Right heart catheterization for the measurements of mean pulmonary artery pressure (Ppa), left atrial pressure estimated from occluded Ppa (Ppao), pulmonary capillary pressure (Pcp) calculated from the Ppa decay curve after balloon occlusion, and cardiac output (Q); inferior vena cava balloon for the control of Q by manipulation of venous return; ventilation in hyperoxia (fraction of inspired O2, 0.4) or in hypoxia (Fio2, 0.1); inhibition of cyclooxygenase by indomethacin (Indo); inhibition of nitric oxide synthase by NG-nitro-l-arginine (L-NA); inhibition of heme oxygenase by mesoporphyrin IX (SnMP); inhalation of nitric oxide (20 ppm); and inhalation of carbon monoxide (100 ppm). MEASUREMENTS AND MAIN RESULTS: The first seven dogs were weak responders to hypoxia as assessed by a hypoxia-induced increase in the gradient between Ppa and Ppao, measured at one level of Q kept constant, by an average of only 2 mm Hg (p = NS). This HPV was markedly increased by the combined administration of Indo and L-NA. A further enhancement of HPV was observed after the addition of SnMP, leading to severe pulmonary hypertension with an average increase in Ppa to 39 mm Hg. Inhaled nitric oxide inhibited HPV only after the combined administration of Indo, L-NA, and SnMP. Inhaled carbon monoxide had no effect. The next 12 dogs were stronger responders to hypoxia, as assessed by a hypoxia-induced increase in the gradient between Ppa and Ppao, measured at several levels of Q, by an average of 3 mm Hg (p <.05). This HPV was of the same magnitude after administration of placebo (n = 6) or SnMP (n = 6). Addition of Indo enhanced HPV to the same extent in the placebo and in the SnMP groups. Addition of L-NA induced a further enhancement of HPV, which was, however, greater in the SnMP group. There was a slight increase in the capillary-venous segment relative to the arterial segment in hypoxic conditions, but the partitioning of pulmonary vascular resistance was otherwise unaffected by nitric oxide, carbon monoxide, or PGI2. CONCLUSIONS: Endogenous carbon monoxide modulates canine HPV only in the absence of nitric oxide. The vasodilation mediated by nitric oxide, PGI2, or carbon monoxide is essentially distributed between proximal and distal sites proportionally to the degree of constriction produced during hypoxia.
Descriptors: carbon monoxide, hypoxic pulmonary vasoconstriction (HPV), prostacyclin (PGI2), nitric oxide.

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, P.M. and S. Kraman (2003). A new fractal pattern of branching of the canine airway. FASEB Journal 17(4-5): Abstract No. 875.7. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: respiratory system, lung, animal model, respiration, fractal pattern, irregular dichotomized fractal pattern, parent daughter pattern.

Wiedemann, K., E. Fleischer, and P. Dressler (2002). Zur Geschichte der Seitentrennung der Atemwege. Anasthesiol Intensivmed Notfallmed Schmerzther. 37(1): 8-15. ISSN: 0939-2661.
Abstract: Techniques to separate the airways to both lungs were employed in the laboratory by renowned physiologists like Pfluger and C. Bernard to study gas exchange. Pfluger's catheter, as used by Wolffberg in 1871 in the dog, essentially constituted an early example of endobronchial single lumen tube, and was to be the first airway separator introduced into man by Loewy and v. Schrotter in 1905 in experiments on circulation. As a variation of this device the carinal hook made ist appearance used by Hess in 1912 in rabbits. While the endobronchial catheters afforded airtight access to only one lung at a time for concomitantly studying ventilation in both lungs, a short tracheal cannula was combined with one introduced into the left main bronchus by Head in 1889, constituting as it were the prototype of double lumen (DL) tubes applicable to rabbits and turtles even. Werigo described 1892 a coaxial DL-tracheostomy cannula for dogs which construction principle was adopted in the first DL-bronchoscope used in man. In lung surgery during the 30s and 40s the ventilated lung was prevented from drowning by pus or secretions from the lung under surgery by sealing off ist main bronchus, either by endobronchial intubation or by a bronchial blocker inserted alongside the endotracheal tube. This principle gave rise to sophisticated devices, from the fixed combination of tube and blocker to the present-day tube housing a movable blocker. Remarkably, DL-intubation in its proper sense then was performed in bronchospirometry only. This technique was introduced by Jacobaeus upon suggestion of Liljestrand when dissatisfied with the restriction to sequential spirometry by customary bronchoscopic catheterization, relying on Frenckner's ingenious DL-bronchoscope. Rubber DL-tubes were developed by Gebauer 1939 and Zavod 1940 exclusively with bronchospirometry in mind, even E. Carlens primarily constructed his tube to improve this procedure. After its usage in over 100 bronchospirometries it was introduced for the first time in November 1949 for its familiar purpose: the resection of a tuberculous abscess in the right upper lobe. Once introduced into thoracic anaesthesia, the DL-principle so far fostered a wide variety of tube designs.
Descriptors: bronchi, anatomy, histology, artificial respiration, history of techniques used, literature review, instrumentation, methods, anesthesiology.

Wilson, S.M., C.E. Mcallister, and J.R. Hume (2003). Ip3 and ryanodine receptors and capacitative ca2+ entry in canine pulmonary arterial myocytes. Biophysical Journal 84(2 Part 2): 391A. ISSN: 0006-3495.
NAL Call Number: 442.8 B5238
Descriptors: cardiovascular system, transport and circulation, metabolism, respiratory system, respiration

Yasukawa, T. (2002). Effects of inversed ratio ventilation (irv) on intracranial pressure (icp) in dogs with pulmonary edema. Kawasaki Igakkai Shi 28(4): 269-278. ISSN: 0386-5924.
Abstract: Although correlation between variations in the inspiratory to expiratory ratio (I:E ratio) and intracranial pressure (ICP) has not been clarified, the study of Mihira showed that IRV (at I:E ratios of 1.7:1, 2.3:1, and 4:1) does not influence ICP in dogs with normal or elevated ICP. In order to estimate the influence of lowered lung compliance on ICP during IRV, an additional study was designed to observe the effects of the I:E ratio=1:2 to 4:1 on ICP in 10 dogs with pulmonary edema induced by Oleic acid. Following baseline measurement of control ventilation (I:E ratio=1:2), lung edema was induced by venous injection of Oleic acid (0.05 mL/kg). After verifying the reduction of lung compliance, four different I:E ratios were applied in the order of I:E=1:2, 1.7:1, 2.3:1, and 4:1. Throughout the period of these measurements, PaCO2 constantly maintained normocapnia and arterial blood pressure was kept within normal range. Intracranial hemodynamics (ICP, cerebral perfusion pressure), lung mechanics (mean airway pressure (mAWP), peak inspiratory pressure (PIP), lung compliance), systemic hemodynamics (mean arterial pressure, mean pulmonary artery pressure, central venous pressure, cardiac output), and blood gases were measured at 30 min under every I:E ratio ventilatory mode. In these dogs with pulmonary edema, mAWP significantly increased during IRV in comparison with that during control ventilation (p<0.05), but there was no significant difference in PIP between control ventilation and IRV. ICP remained unchanged during IRV (12.5+-4.2, 10.0+-2.9, 11.1+-2.2, 11.3+-2.7 at I:E=1:2, 1.7:1, 2.3:1 and 4:1, respectively). This study suggested that IRV (at I:E ratios of 1.7:1, 2.3:1, and 4:1), which can minimize ventilator-induced lung injury, has no influence on ICP. Therefore, IRV may be one beneficial option as ventilation strategy for acute respiratory distress syndrome with intracranial hypertension.
Descriptors: methods and techniques, nervous system, neural coordination, respiratory system, respiration, acute respiratory distress syndrome, respiratory system disease, intracranial hypertension, nervous system disease, vascular disease, pulmonary edema, inversed ratio ventilation, laboratory techniques, intracranial pressure, mean airway pressure.
Language of Text: Japanese.

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