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Information Resources on the Care and Welfare of Dogs: Animal Welfare Information Center
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Anesthesia and Analgesia

Ambrisko, T.D. and Y. Hikasa (2003). The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs. Canadian Journal of Veterinary Research 67(1): 64-67. ISSN: 0830-9000.
NAL Call Number: SF601.C24
Abstract: This study aimed to compare the antagonistic effects of atipamezole (40, 120, and 320 mug/kg, IM), yohimbine (110 mug/kg, IM), and saline on neurohormonal and metabolic responses induced by medetomidine (20 mug/kg, IM). Five beagle dogs were used in each of the 5 experimental groups in randomized order. Blood samples were taken for 6 h. Medetomidine significantly decreased norepinephrine, epinephrine, insulin, and nonesterified fatty acid levels, and increased plasma glucose levels. Both atipamezole and yohimbine antagonized these effects. The reversal effect of atipamezole was dose-dependency, except on epinephrine. Yohimbine caused prolonged increases in plasma norepinephrine and insulin levels compared to atipamezole, possibly because of its longer half-life elimination. Only yohimbine increased the cortisol levels. Neither glucagon nor lactate levels changed significantly. Based on these findings, when medetomidine-induced sedation is antagonized in dogs, we recommend using atipamezole IM, from 2- to 6-fold the dose of medetomidine, unless otherwise indicated.
Descriptors: anesthesiology, behavior, neural coordination, pharmacology, metabolic response, neurohormonal response, surgical stress, yohimbine, imidazoles, antagonists, medetomidine, blood composition, epinephrine, norepinephrine, blood glucose, insulin, blood lipids, fatty acids.

Ando, K., A. Sugiyama, Y. Satoh, Y. Nakamura, H. Routledge, and K. Hashimoto (2004). Prediction of drug-induced qt prolongation using halothane-anesthetized canine model: Comparison of risperidone and olanzapine. Journal of Pharmacological Sciences 94 (Suppl. 1): 270P. ISSN: 1347-8613.
Descriptors: veterinary medicine, schizophrenia, HIS bundle electrocardiogram, diagnostic techniques, anesthesia, QT prolongation, drug induced.
Notes: Meeting Information: 77th Annual Meeting of the Japanese Pharmacological Society, Osaka, Japan; March 8-10, 2004.

Ando, K., A. Sugiyama, A. Takahara, Y. Satoh, and K. Hashimoto (2003). Cardiovascular effects of y-27632, a selective rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model. Journal of Pharmacological Sciences 91 (Suppl. I): 157P. ISSN: 1347-8613.
Descriptors: cardiovascular system, transport and circulation, pharmacology, sympathetic reflex, halothane.
Notes: Meeting Information: 76th Annual Meeting of the Japanese Pharmacological Society, Fukuoka, Japan; March 24-26, 2003.

Ezzine, S. and F. Varin (2005). Interstitial muscle concentrations of rocuronium under steady-state conditions in anaesthetized dogs: actual versus predicted values. British Journal of Anaesthesia 94(1): 49-56. ISSN: 0007-0912.
Abstract: Introduction. The objective of this study was to compare rocuronium effect (Ce) and peripheral (C2) compartment concentrations predicted by pharmacokinetic-pharmacodynamic (PK-PD) modelling with those measured in plasma (Cp) and in the interstitial fluid of muscle tissue (CISF,u) by microdialysis in anaesthetized dogs. Methods. After approval by the Animal Care Committee, eight adult male dogs with a body weight ranging from 7 to 18 kg were anaesthetized with pentobarbital. Each dog received a 2-min rocuronium infusion of 0.15 mg kg-1 min-1 followed by a 118-min infusion of 60 mug kg-1 min-1 via the right jugular vein. Arteriovenous gradient across the hindlimb was measured at 40, 60, 100 and 120 min. Three microdialysis samples were collected at 40-min intervals. Once the infusion stopped, arterial samples were collected every 2 min for the first 10 min and every 20 min for the next 120 min. Neuromuscular function was monitored using train-of-four stimulation until full recovery. Dogs were then killed and a biopsy of muscle tissue was performed (Cm). Results. At steady state, the mean CISF,u value was 1353 ng ml-1. After correction for the unbound fraction in plasma, the mean Ce,corr and C2,corr were 1681 and 1481 ng ml-1, respectively. At the terminal sampling point, Cm was 10-fold higher than Cp. Conclusion. Unbound concentration of rocuronium measured in the muscle interstitial fluid under steady-state conditions confirms that parametric PK-PD modelling gives reliable estimates of effect site concentrations. Rocuronium accumulates in muscle tissue, probably by non-specific protein binding in the interstitial space.
Descriptors: anesthesiology, pharmacology, anesthesia, microdialysis, laboratory techniques, muscle biopsy, animal care committee.

Flecknell, P. (1997). Assessment and alleviation of post-operative pain. Animal Welfare Information Center Newsletter 8(3/4): 8-14. ISSN: 1050-561X.
NAL Call Number: aHV4701.A952
Descriptors: surgery, pain, laboratory animals, animal welfare, analgesics, mice, rats, guinea pigs, rabbits, ferrets, primates, pigs, sheep, dogs, cats.

Fox, S.M., D.J. Mellor, C.R.O. Lawoko, H. Hodge, and E.C. Firth (1998). Pain-induced distress in canine ovariohysterectomy and its alleviation with perioperative butorphanol. Veterinary Surgery 27(2): 173. ISSN: 0161-3499.
NAL Call Number: SF911.V43
Descriptors: pain, ovariectomy, surgery, butorphanol.

Fujii, Y., A. Uemura, and H. Toyooka (2003). The effect of inhaled colforsin daropate on contractility of fatigued diaphragm in dogs. Anesthesia and Analgesia 96(4): 1032-1034. ISSN: 0003-2999.
Abstract: We studied the effect of inhaled colforsin daropate, a water-soluble forskolin derivative, on the contractility of fatigued diaphragm in dogs. Animals were divided into 3 groups of 8. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation applied for 30 min. Immediately after the end of the fatigue-producing period, Group 1 received inhaled vehicle, Group 2 received inhaled colforsin daropate 0.1 mg/mL, and Group 3 received inhaled colforsin daropate 0.2 mg/mL. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After fatigue was produced, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P<0.05), and there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate inhalation, Pdi at both stimuli increased from fatigued values (P<0.05). The increase in Pdi was significantly larger in Group 3 than in Group 2. The integrated electrical activity of the diaphragm did not change in any group. We conclude that inhaled colforsin daropate causes an increase in contractility of fatigued canine diaphragm in a dose-related fashion.
Descriptors: muscular system, pharmacology, colforsin daropate, forskolin, fatigued diaphragm, animal models, contractility.

Fujii, Y., A. Uemura, and H. Toyooka (2003). Midazolam-induced muscle dysfunction and its recovery in fatigued diaphragm in dogs. Anesthesia and Analgesia 97(3): 755-758. ISSN: 0003-2999.
Abstract: Midazolam, widely used for sedation and anesthesia, decreases contractility in nonfatigued diaphragm; however, its effects on contractility in fatigued diaphragm that are implicated as a cause of respiratory failure have not been established. We therefore studied the effects of midazolam on diaphragm muscle function and recovery in fatigued diaphragm. Dogs were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. When fatigue was established, Group I received no study drug; Group II was infused with a sedative dose (0.1 mgcntdotkg-1cntdoth-1) of midazolam; and Group III was infused with an anesthetic dose (0.5 mgcntdotkg-1cntdoth-1) of midazolam. We assessed diaphragm muscle function (contractility and electrical activity) by transdiaphragmatic pressure (Pdi) and integrated electrical activity of the diaphragm (Edi). In the presence of fatigue, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P<0.05), Pdi at high-frequency (100-Hz) stimulation did not change, and Edi to each stimulus did not change. With an infusion of midazolam, in Groups II and III, Pdi at both stimuli and Edi at 100-Hz stimulation decreased from fatigued values (P<0.05). The decrease in Pdi and Edi was more in Group III than in Group II (P<0.05). At 60 min after the cessation of midazolam administration, in Group II, Pdi and Edi recovered from midazolam-induced values (P<0.05) and returned to fatigued values. In Group III, Pdi and Edi did not change from midazolam-induced values. We conclude that midazolam causes, in a dose-related manner, diaphragm muscle dysfunction in fatigued canine diaphragm and that at a sedative dose, but not at an anesthetic dose, midazolam does not delay its recovery.
Descriptors: midazolam, contractility, fatigued diaphragm, analgesia, dogs, respiratory failure.

Gilberto, D.B., S.L. Motzel, A.N. Bone, C.L. Burns, A.H. Zeoli, K.E. Lodge, and T.L. Goode (2002). Use of three infusion pumps for postoperative administration of buprenorphine or morphine in dogs. Journal of the American Veterinary Medical Association 220(11): 1655-1660. ISSN: 0003-1488.
NAL Call Number: 41.8 AM3
Abstract: The results of using infusion pump methods (implantable osmotic pump, preset disposable infusion pump and programmable infusion pump) for postoperative delivery of morphine and buprenorphine in dogs undergoing abdominal surgery are discussed. In evaluating the methods studied, it appeared that the use of the programmable infusion pump for administration of buprenorphine provided the most consistent analgesia. The use of the preset infusion pump for administration of morphine was fairly simple and provided good analgesia, and the cost was similar to that associated with epidural administration of morphine. The least successful method in this study was the use of the implantable osmotic pumps for buprenorphine administration. This method was labour intensive and invasive and only provided minimal analgesia.
Descriptors: anesthesia, anesthetics, analgesics, benzodiazepines, morphine, postoperative care, surgical instruments, surgical operations, dogs.

Gilberto, D.B., S.L. Motzel, and S.R. Das (2003). Postoperative pain management using fentanyl patches in dogs. Contemporary Topics in Laboratory Animal Science 42(4): 21-26. ISSN: 1060-0558.
NAL Call Number: SF405.5.A23
Abstract: To the ability of the fentanyl patch to control pain in a postoperative canine model, we provided two male beagles with 25-mug/h patches and two with 50-mug/h patches 24 h prior to surgery. Each animal underwent a major abdominal surgical procedure to place three separate catheters with associated vascular access ports. Serum plasma levels of fentanyl were analyzed at multiple time points throughout the study period. Animals were subjectively assessed for postoperative pain by using a Simple Descriptive Scale at regular intervals postoperatively. Other parameters observed and recorded included heart and respiration rates, rectal temperature, appetite, and activity. The fentanyl patch appeared to adequately control postoperative pain in our canine abdominal surgical model. Three animals demonstrated mild pain 1 to 2 h postoperatively. Two animals, one from each dose group, showed mild pain 8 h postoperatively. Mild pain is commensurate with USDA category C, which encompasses procedures that do not result in more than momentary or slight pain or distress and do not require intervention. At no other time points were any of the animals considered to be in pain. Our study also suggested that increased subcutaneous fat delayed the rate of absorption of fentanyl. The lower body-weight beagles, which had the 25-mug/h patches, reached reported human serum analgesic levels within 8 h after placement, whereas the heavier beagles with the 50-mug/h patches reached human serum analgesic levels 12 h after placement. Fentanyl concentrations remained at the reported human analgesic levels in all animals between 2 to 4 h after the patches were removed. Regardless of the dose, decreases in heart rate, respiration rate, and temperature were observed in all four animals 12 h after placing the patches. Issues regarding the regulatory requirements to prevent drug abuse, the side effects and potency of fentanyl, and the prolonged duration of action as a transdermal system should be addressed by the veterinarian when considering usage of this analgesic method.
Descriptors: nervous system, neural coordination, pharmacology, postoperative pain, nervous system disease, abdominal surgery, experimental surgical techniques, laboratory techniques, appetite, heart rate, rectal temperature, respiration rate.

Hansen, B.D. (2003). Assessment of pain in dogs: veterinary clinical studies. ILAR Journal 44(3): 197-205. ISSN: 1084-2020.
NAL Call Number: QL55.A1143
Abstract: Hundreds of thousands of animals are presented to US veterinarians annually for surgery or for evaluation of painful disease. This large population offers the opportunity for clinical research of both acute and chronic pain syndromes. Although there is growing interest by veterinary clinical specialists to explore the nature of animal pain and how best to treat it, this resource is relatively unknown to the pain research community. Computer-assisted collection of behavioral data has created new opportunities for characterizing the pain experience in animal species for the benefit of both animals and humans. This review describes the current state of veterinary clinical pain studies in dogs and an application of computer-assisted behavioral analysis.
Descriptors: surgery, disease, pain, assessment, chronic, acute, surgery, behavioral paramenters, behavioral analysis.

Horstman, C.L., M.G. Conzemius, R. Evans, and W.J. Gordon (2004). Assessing the efficacy of perioperative oral carprofen after cranial cruciate surgery using noninvasive, objective pressure platform gait analysis. Veterinary Surgery 33(3): 286-292. ISSN: 0161-3499.
NAL Call Number: SF911.V43
Abstract: OBJECTIVE: To document, using pressure platform gait analysis, the effect of perioperative oral carprofen on limb function and pain after cranial cruciate ligament surgery in dogs. STUDY DESIGN: Blinded, prospective clinical investigation. ANIMALS: Twenty dogs with naturally occurring unilateral cranial cruciate disease. PROCEDURE: Physiologic indices, subjective pain scoring, and pressure platform gait analyses were performed before and 24, 48, and 72 hours after surgery. Correlations were assessed between methods of evaluation and the data was compared across treatment groups. RESULTS: No strong correlations were noted between physiologic data, subjective scoring systems, or gait analysis data at a walk or stance. Although average measures of limb function were nearly twice as large in dogs treated with carprofen, no significant differences between groups over time were identified. No significant differences were noted in any other measure of pain or limb function. Power analysis of peak vertical force at a walk indicated that significant difference would have been detected had the number of dogs in each group been increased to 35. CONCLUSION: When limb function was assessed with pressure platform gait analysis no statistical difference was noted between groups with respect to PVF and VI at a walk or stance, although average ground reaction forces for dogs in the carprofen group were greater than the traditional pain management group at all time points. CLINICAL RELEVANCE: Oral carprofen appears to provide some benefit for the treatment of postoperative orthopedic pain.
Descriptors: unilateral cranial cruciate disease, pain scoring, pressure platform gait analysis, oral carprofen, pstoperative orthopedic pain.

Hu, G., M.R. Salem, and G.J. Crystal (2002). Isoflurane abolishes platelet-induced enhancement of superoxide production by neutrophils. In: 2002 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 12-16, 2002, Orlando, FL, USA, p. Abstract No. A 695.
Descriptors: isoflurane, spectrum analysis techniques, neutrophil-induced cardiac dysfunction, superoxide, dogs.

Ito, H. and P.A. Murray (2003). Effects of desflurane on endothelium-dependent vasorelaxation in pulmonary arteries. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 1467.
Descriptors: inhalation anesthetics, vasorelaxation, pulmonary circulation, in vitro study, desflurance, canine pulmonary arterial rings, cardiovascular system.

Johnson, E.E., H. Gibson, B. Nicol, J. Zanzinger, P. Widdowson, M. Hawthorn, G. Toth, J. Farkas, R. Guerrini, and D.G. Lambert (2003). Characterization of nociceptin/orphanin fq binding sites in dog brain membranes. Anesthesia and Analgesia 97(3): 741-747. ISSN: 0003-2999.
Abstract: Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor (NOP), whose characteristics in the dog are unknown. We therefore compared (3H)N/OFQ binding in dog and rat brain membranes. Radioligand saturation/competition studies with these membranes and leucyl-(3H)N/OFQ(1-17)OH or the novel radioligand (3H)N/OFQ(1-13)NH2 were performed to determine receptor density and ligand affinity. The density of classic opioid receptors was determined by using (3H)diprenorphine. Leucyl-(3H)N/OFQ(1-17)OH binding was concentration dependent and saturable in dog (maximum binding capacity (Bmax), 28.7+-2.8 fmol/mg of protein; equilibrium dissociation constant as negative log (pKd), 10.27+-0.11) and rat (Bmax, 137.0+-12.9 fmol/mg of protein; pKd, 10.41+-0.05). In comparison, the Bmax and pKd of (3H)diprenorphine were, respectively, 77.7+-5.3 fmol/mg of protein and 9.74+-0.09 in dog and 79.1+-18.2 fmol/mg of protein and 9.51+-0.04 in rat. In dog, (3H)N/OFQ(1-13)NH2 binding to NOP receptors was also saturable (Bmax, 23.7+-2.0 fmol/mg of protein; pKd, 10.16+-0.12). In both species, leucyl-(3H)N/OFQ(1-17)OH was displaced by various NOP ligands. Dynorphin A, N/OFQ(1-5)NH2, and nocistatin were essentially inactive. There was a significant positive correlation (r2=0.95; P<0.0001) between pKi values (an estimate of affinity) obtained in displacement studies in rat and dog. We have demonstrated a low density of NOP receptors, measured with two radioligands, in dog, and these receptors display a high degree of pharmacological similarity with those natively expressed in the rat.
Descriptors: membranes, cell biology, nervous system, neural coordination, pharmaceuticals, pharmacology .

Johnson, E.E., J. Mcdonald, B. Nicol, R. Guerrini, and D.G. Lambert (2004). Functional coupling of the nociceptin/orphanin fq receptor in dog brain membranes. Brain Research 1003(1-2): 18-25. ISSN: 0006-8993.
Descriptors: nociceptin, orphanin FQ, dog brain, pharmacology, Chinese hamsters.

Junior, P.N., N.R. Villela, L.R. Carvalho, and A.B. Teixeira (2003). Renal effects of dexmedetomidine. Experimental study in dogs. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 502.
Descriptors: urinary system, general anesthesia, heart rate, dexmedetomidine, alpha2-adrenergic agonist, dosages, dogs, renal hemodynamics, diuretic.

Kabara, S., K. Hirota, E. Hashiba, H. Yoshioka, and A. Matsuki (2002). Propofol antagonizes methacholine-induced bronchoconstriction in dogs with and without vagotomy. In: 2000 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 16-18, 2000, San Francisco, CA, USA, p. Abstract No. 1325.
Descriptors: propofol, vagal nerve blockage, muscular system, methacholine (Mch)-induced bronchoconstriction, vagotomy, experimental surgical techniques, laboratory techniques, bronchial cross sectional area, pentobarbital, mongrel dogs, relaxant effects.

Kehl, F., J.F. Ladisa, J.R. Kersten, D.C. Warltier, and P.S. Pagel (2003). Isoflurane adversely alters active and passive left atrial function and impairs left atrial-left ventricular coupling in dogs with pacing-induced cardiomyopathy as evaluated using pressure-volume relations. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 755.
Descriptors: anesthesiology, active, passive left atrial function, adverse alterations, end systolic pressure volume relations, left atrial emptying fraction, left atrial myocardial contractility, left atrial stroke volume, left atrial stroke work, left atrial left ventricular coupling, pressure volume relations, steady state pressure volume diagram, total reservoir volume, dose related declines, pacing-induced cardiomyopathy, isoflurane.

Kehl, F., B. Mraovic, P.S. Pagel, D.C. Warltier, and J.R. Kersten (2002). Hyperglycemia is an interactive determinant of myocardial infarct size during isoflurane-induced preconditioning. In: 2001 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 13-17, 2001, New Orleans, LA, USA, p. Abstract No. A 690.
Descriptors: hyperglycemia, myocardial infarction, heart disease, vascular disease, ischemic preconditioning, laboratory techniques, heart rate, volatile anesthetics, cardioprotective effects, isoflurane.

Kerbaul, F., B. Rondelet, S. Motte, P. Fesler, I. Hubloue, P. Ewalenko, R. Naeije, and S. Brimioulle (2004). Isoflurane and desflurane impair right ventricular-pulmonary arterial coupling in dogs. Anesthesiology 101(6): 1357-1362. ISSN: 0003-3022.
Abstract: Background. Halogenated anesthetics depress left ventricular function, but their effects on the right ventricle have been less well studied. Therefore, the authors studied the effects of isoflurane and desflurane on puhnonary arterial (PA) and right ventricular (RV) properties at baseline and in hypoxia. Methods: Right ventricular and PA pressures were measured by micromanometer catheters, and PA flow was measured by an ultrasonic flow probe. PA mechanics were assessed by flowpressure relations and by impedance spectra derived from flow and pressure waves. RV contractility was assessed by end-systolic elastance (Ees), RV afterload was assessed by effective PA elastance (Ea), and RV-PA coupling efficiency was assessed by the Ees:Ea ratio. Anesthetized dogs were randomly assigned to increasing concentrations (0.5, 1, and 1.5 times the minimum alveolar concentration) of isoflurane (n = 7) or desflurane (n = 7) in hyperoxia (fraction of inspired oxygen, 0.4) and hypoxia (fraction of inspired oxygen, 0.1). Results: Isoflurane and desflurane had similar effects. During hyperoxia, both anesthetics increased PA resistance and characteristic impedance, increased Ea (isoflurane, from 0.82 to 1.44 mmHg/ml; desflurane, from 0.86 to 1.47 mmHg/ml), decreased Ees (isoflurane, from 1.09 to 0.66 mmHg/ml; desflurane, from 1.10 to 0.72 mmHg/ml), and decreased Ees:Ea (isoflurane, from 1.48 to 0.52; desflurane, from 1.52 to 0.54) in a dose-dependent manner (all P < 0.05). Hypoxia increased PA resistance, did not affect characteristic impedance, increased afterload, and increased contractility. During hypoxia, isoflurane and desflurane had similar ventricular effects as during hyperoxia. Conclusions: Isoflurane and desflurane markedly impair RV-PA coupling efficiency in dogs, during hyperoxia and hypoxia, both by increasing RV afterload and by decreasing RV contractility.
Descriptors: anesthesiology, blood pressure measurement, laboratory techniques, hyperoxia, hypoxia.

Kroin, J.S., R.J. Mccarthy, R.D. Penn, T.J. Lubenow, and A.D. Ivankovich (2003). Continuous intrathecal clonidine and tizanidine in conscious dogs: analgesic and hemodynamic effects. Anesthesia and Analgesia 96(3): 776-782. ISSN: 0003-2999.
Abstract: Alpha-2-adrenergic agonists, such as clonidine, produce antinociception in animal pain models after intrathecal administration. However, clinical usage is limited by cardiovascular side effects. To investigate alternative alpha2-adrenergic agonists as analgesics, we implanted six dogs with an intrathecal catheter and infusion pump. After baseline saline infusion, animals received clonidine or tizanidine (crossover study) each week at escalating doses of 125-750 mug/h. Analgesia, blood pressure, heart rate, respiratory rate, sedation, and coordination were evaluated. A 28-day safety study was performed with another nine dogs receiving intrathecal tizanidine (3 or 6 mg/d) or saline. Equal doses of clonidine and tizanidine produce the same antinociception in thermal withdrawal tests. Blood pressure was reduced with 125-500 mug/h of clonidine, but not with tizanidine at any dose. Clonidine 250 mug/h reduced heart rate by 45.8%, and five of six animals had bradyarrhythmias (marked bradycardia), whereas tizanidine decreased heart rate by 15.1% without arrhythmias, even at the largest dose. Respiratory rate decreased with 250 mug/h of clonidine and larger doses. Sedation or incoordination occurred only at the largest dose for either drug. The safety study indicated that 3 mg/d of tizanidine in dogs produced no side effects or histopathologic changes. Tizanidine may be a useful alternative in patients experiencing cardiovascular side effects with intrathecal infusion of clonidine
Descriptors: cardiovascular system, transport and circulation, nervous system, neural coordination, pharmacology, hemodynamics.

Kyles, A.E., E.M. Hardie, B.D. Hansen, and M.G. Papich (1998). Comparison of transdermal fentanyl and intramuscular oxymorphone on post-operative behaviour after ovariohysterectomy in dogs. Research in Veterinary Science 65(3): 245-251. ISSN: 0034-5288.
NAL Call Number: 41.8 R312
Abstract: The effects of transdermal fentanyl and IM oxymorphone on behavioural and physiological responses, after ovariohysterectomy in dogs, were investigated. The study involved three groups of 10 dogs: fentanyl/surgery (FS), oxymorphone/surgery (OS), fentanyl/control (FC). A transdermal fentanyl delivery system (50 micrograms hour-1) (FS and FC) was applied 20 hours before surgery, or IM oxymorphone (OS) was administered. After ovariohysterectomy (FS and OS) or anaesthesia alone (FC), dogs were continuously videotaped for 24 hours and a standardised hourly interaction with a handler performed. The videotapes were analysed, and interactive and non-interactive behaviours evaluated. In addition, pain and sedation scores, pulse and respiratory rates, rectal temperature, arterial blood pressure, plasma cortisol and plasma fentanyl concentrations were measured. This study showed that transdermal fentanyl and IM oxymorphone (0.05 mg kg-1) produced comparable analgesic effects over a 24 hour recording period. IM oxymorphone produced significantly more sedation and lower rectal temperatures than transdermal fentanyl. There were no significant differences between groups in respiratory and heart rates, and arterial blood pressures.
Descriptors: bitches, fentanyl, transdermal application, ovariectomy, hysterectomy, analgesics, intramuscular injection, pain, drug effects, efficacy, animal behavior, body temperature, hydrocortisone.

Machon, R. (1999). The recovery period care for cats and dogs recovering from general anaesthesia. Veterinary Continuing Education 190: 211-216. ISSN: 0112-9643.
Descriptors: anesthesia, recovery, cats, dogs.

Maekawa, T., S. Cho, S. Takahashi, S. Tomiyasu, and K. Sumikawa (2003). The effects of propofol on contractility and oxygen balance in normal and acute ischemic myocardium. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 689.
Descriptors: acute heart failure, heart disease, myocardial ischemia, vascular disease, Scheffe's f test, analysis of variance for repeated measures, coronary microembolization model, experimental surgical techniques, laboratory techniques, lactate extraction ratio, myocardial contractility, oxygen balance, segment shortening, systemic, regional coronary hemodynamics, propofol, mongrel dogs.

Manisterski, Y., Z. Vaknin, R. Ben Abraham, O. Efrati, D. Lotan, M. Berkovitch, A. Barak, Z. Barzilay, and G. Paret (2002). Endotracheal epinephrine: A call for larger doses. Anesthesia and Analgesia 95(4): 1037-1041. ISSN: 0003-2999.
Abstract: Endotracheal administration of epinephrine 0.02 mg/kg (twice the IV dose) is recommended when IV access is unavailable during cardiopulmonary resuscitation. The standard IV dose has been considered too small for the endotracheal route by causing a detrimental decrease of arterial blood pressure (BP), presumably mediated by the beta-adrenergic receptor unopposed by alpha adrenergic vasoconstriction. We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase BP. After injecting normal saline (control), saline-diluted epinephrine (0.02, 0.035, 0.1, 0.2, and 0.3 mg/kg) was injected into the endotracheal tube of five anesthetized dogs at least 1 wk apart. Arterial blood samples for blood gases were collected before and at 14 time points up to 60 min after the drug administration. Heart rate and arterial BP were continuously monitored with a polygraph recorder. Only the 0.3 mg/kg dose successfully caused an increase in BP, observed 2 min after administration, and lasting for 10 min. An early decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. IMPLICATIONS: We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase arterial blood pressure (BP). A decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. Clinical studies using larger doses of endotracheal epinephrine and their use as first-line therapy in cardiac arrest are warranted.
Descriptors: animal model, endotracheal administration, cardiopulmonary resuscitation, arterial blood pressure, clinical studies, cardiac arrest, endotracheal epinephrine, blood samples, blood gases.

Mizumoto, K. and P.A. Murray (2002). Halothane and desflurane potentiate alpha adrenoreceptor-mediated pulmonary artery contraction: role of the endothelium and vascular smooth muscle. In: 2002 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 12-16, 2002, Orlando, FL, USA, p. Abstract No. A 1298.
Descriptors: inhalational anesthetics, halothane, desflurane, pulmonary vasoconstrictor response, cellular mechanisms, in vitro study, endothelium, pulmonary vascular smooth muscle, alpha adrenoreceptor activationcardiovascular system, vasorelaxant response.

Mizumoto, K. and P.A. Murray (2003). Desflurane potentiates alpha adrenoreceptor-mediated pulmonary artery contraction: involvement of PKC, Rho kinase and tyrosine kinases. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers Annual Meeting, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 1523.
Descriptors: desflurane (DES), arterial smooth muscle, cardiovascular system, alpha adrenoreceptor-mediated contraction, canine, myofilament, pharmacology.

Murray, P.A. and X. Ding (2003). Ketamine attenuates acetylcholine-induced contraction in pulmonary veins. In: 2003 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers Annual Meeting, October 11-15, 2003, San Francisco, CA, USA, Vol. 99, p. Abstract No. A 1468.
Descriptors: anesthetic agents, pulmonary venous tone, ketamine, acetylcholine (Ach), cardiovascular system, vasoconstrictor cyclooxygenase metabolites, isolated canine pulmonary venous rings.

Murrell, J.C., H.N.M. De Groot, A.J. Venker Van Haagen, W.E. Van Den Brom, and L.J. Hellebrekers (2004). Middle-latency auditory-evoked potential in acepromazine-sedated dogs. Journal of Veterinary Internal Medicine 18(2): 196-200. ISSN: 0891-6640.
NAL Call Number: SF601.J65
Abstract: The middle-latency auditory-evoked potential (MLAEP) has been investigated as means of monitoring anesthesia in dogs. The goals of this study were to develop a technique to record MLAEPs in awake dogs and to determine the effects of sedation. The MLAEP was recorded in 12 dogs with and without sedation with acepromazine. Three needle electrodes were inserted SC. Click stimuli were delivered biaurally. Signal acquisition, averaging, and analysis were performed by software developed in-house. Signals were recorded for 128 milliseconds, and the responses to 1,024 stimuli were averaged. The waveforms from 10 recordings were averaged, and the amplitudes and latencies of peaks that could be consistently identified were measured. Data measured were compared by means of a paired 2-sided Student's t-test. Interpretable MLAEPs were recorded in 10 of the 12 dogs. Three peaks were consistently identified (Pa, Nb, and Pb). The latencies of these peaks were significantly (P=.032, .035, and .028, respectively) shorter in awake (mean+-SD milliseconds) (Pa=18.85+-1.36, Nb=30.50+-3.55, and Pb=47.70+-5.53) than in sedated (Pa=22.40+-3.88, Nb=35.75+-6.77, and Pb=55.30+-10.55) dogs. The Pb amplitude was not significantly different (2.51+-1.30 muV awake and 2.19+-1.10 muV sedated). This study demonstrates that acepromazine sedation causes changes in MLAEP.
Descriptors: pharmacology, veterinary medicine, anesthesia monitoring, laboratory techniques, middle latency auditory evoked potential recording, laboratory techniques, middle latency auditory evoked potential.

Stucke, A.G., E.A.E. Stuth, V. Tonkovic Capin, J.P. Kampine, and E.J. Zuperku (2003). Sevoflurane depresses overall excitatory drive but not the postsynaptic glutamate receptor response to medullary inspiratory neurons in a decerebrate dog model. FASEB Journal 17(4-5): Abstract No. 302.2. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: decerebrate vagotomy, experimental surgical techniques, multibarrel micropipette, neuronal discharge frequency, overall excitatory drive, overall glutamatergic excitation, postsynaptic glutamate receptor response.
Notes: Meeting Information: FASEB Meeting on Experimental Biology: Translating the Genome, San Diego, CA, USA; April 11-15, 2003.

Takahashi, S., Y. Fujii, T. Hoshi, A. Uemura, M. Miyabe, and H. Toyooka (2003). Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs. Canadian Journal of Anesthesia 50(8): 830-834. ISSN: 0832-610X.
Abstract: Background: Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta1 blocker, landiolol, and milrinone in halothane-anesthetized dogs. Methods: Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothane. Hemodynamic measurements were made at baseline, 30 min after starting the milrinone (0.5 mugcntdotkg-1cntdotmin-1) or normal saline infusion (n=9 in each), then 30 min after each change in the dose of landiolol infusion. The tested doses of landiolol were 10, 100, and 1000 mugcntdotkg-1cntdotmin-1. Results: Landiolol (gtoreq=10 mugcntdotkg-1cntdotmin-1) has significant and comparable negative chronotropic effects in both groups of dogs. While it also has significant negative inotropic effects in both groups, such effects are significantly attenuated in the dogs treated with milrinone. Conclusion: Milrinone is effective to attenuate the negative inotropic effects of landiolol in halothane-anesthetized dogs.
Descriptors: high dose beta-blocker therapy, milrinone, hemodynamic effects, halothane anesthesia.

Tanaka, H. and P.A. Murray (2002). Propofol attenuates alpha adrenoreceptor mediated contraction in pulmonary veins. In: 2002 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 12-16, 2002, Orlando, FL, USA, p. Abstract No. A 1300.
Descriptors: propofol, pulmonary arteries, pulmonary venous tone, anesthetics, alpha adrenoreceptor activation, myofilamnet, isolated canine pulmonary venous rings.

Tanaka, H. and P.A. Murray (2002). Propofol inhibits ca2+ influx but increases myofilament ca2+ sensitivity during muscarinic receptor activation in pulmonary veins. In: 2002 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 12-16, 2002, Orlando, FL, USA, p. Abstract No. A 1299.
Descriptors: pulmonary edema, endothelium dependent relaxation, pulmonary capillary pressure, transcapillary fluid flux, acetylcholine(ACh), pulmonary venous tone, anesthetic agents, propofol, myofilament Ca2+ sensitivity.

Tanaka, M. and T. Nishikawa (2003). Hemodilution does not alter arterial baroreflex control of heart rate in anesthetized dogs. Anesthesia and Analgesia 96(1): 28-32. ISSN: 0003-2999.
Abstract: The cardiovascular effects of acute normovolemic hemodilution (ANH) are characterized by increased cardiac output and decreased systemic vascular resistance. However, whether arterial baroreflex function is altered by ANH remains undetermined. We assigned 23 anesthetized, mechanically ventilated dogs to mild ANH (hemoglobin, 7-8 g/dL; n=11) or profound ANH (hemoglobin, 4-5 g/dL; n=12) achieved by phlebotomy and simultaneous exchange with lactated Ringer's solution at 1:3 ratio to maintain constant central venous pressure and pulmonary artery occluded pressure. Baroreflex sensitivity was assessed by measurements of RR intervals of the electrocardiogram and mean arterial blood pressure (MAP) through a femoral artery catheter. Baroreflex responses were triggered by bolus IV injections of phenylephrine (25-75 mug) and nitroprusside (50-100 mug). The linear portion of the baroreflex curves relating RR intervals and MAP were used to determine baroreflex sensitivities. Compared with the predilution period, both ANH groups had significant increases in cardiac output and decreases in systemic vascular resistance (P<0.01), whereas MAP and heart rate (HR) remained unchanged. However, no significant difference was detected between pre-ANH and post-ANH baroreflex sensitivities in either group. Our results indicate that arterial baroreflex control of HR is preserved during ANH to a hemoglobin concentration of 4-5 g/dL in anesthetized dogs.
Descriptors: cardiovascular system, transport and circulation, rr interval, acute normovolemic hemodilution, arterial baroreflex control, cardiac output, heart rate, mean arterial blood pressure, systemic vascular resistance.

Tanimoto, H., H. Ao, A. Yoshitake, Y. Sakanashi, and H. Terasaki (2002). Extracorporeal lung assist does not increase body weight. In: 2001 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 13-17, 2001, New Orleans, LA, USA, p. Abstract No. A 361.
Descriptors: extracorporeal lung assist (ECLA), veterinary medicine, neonatal respiratory distress, arterial blood gas analysis, heparin bonded artificial lung, right femoral artery cannulation, roller pump, urinary catheter, arterial blood pressure, body weight, dogs.

Tsubo, T., H. Okawa, K. Hirota, H. Ishihara, and A. Matsuki (2002). Elimination of ketamine and midazolam from the lungs during pulmonary lavage in dogs. In: 2001 Annual Meeting of the American Society of Anesthesiologists, Abstracts of Scientific Papers, October 13-17, 2001, New Orleans, LA, USA, p. Abstract No. A 370.
Descriptors: respiration, veterinary medicine, alveolar proteinosis, bronchial asthma, cystic fibrosis, double lumen tracheal tube, gas mass spectrography, laboratory techniques, spectrum analysis techniques, pulmonary lavage, single lung ventilation, tracheal intubation, ketamine, midazolam.

Vaisanen, M., M. Raekallio, E. Kuusela, P. Huttunen, J. Leppaluoto, P. Kirves, and O. Vainio (2002). Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. American Journal of Veterinary Research 63(7): 969-975. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: Objective: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanaesthetic medication. Animals: 42 client-owned dogs that underwent elective ovariohysterectomy. Procedure: Each dog was randomly allocated to receive medetomidine (Domitor) and butorphanol tartrate (Torbugesic vet; 20 µg/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate (Plegisil vet) and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanaesthetic medication. Approximately 80 min later, anaesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. Results: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. Conclusions and Clinical Relevance: Results indicate that for preanaesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.
Descriptors: acepromazine, anesthesia, anesthetics, blood pressure, butorphanol, endorphins, epinephrine, heart rate, hydrocortisone, isoflurane, medetomidine, neuroleptics, norepinephrine, propofol, stress, surgical operations.

Wu, W.N., L.A. Mckown, and J.R. Carson (2003). In vitro biotransformation of the analgesic agent, RWJ-51784, in rat, dog and human. European Journal of Drug Metabolism and Pharmacokinetics 28(2): 107-111. ISSN: 0378-7966.
Abstract: RWJ-51784, an analogue of phenyl isoindoles, is a new analgesic agent. The in vitro metabolism of RWJ-51784 was conducted using rat, dog and human hepatic S9 in the presence of an NADPH generating system, and API-ionspray-MS and MS/MS techniques for the metabolite profiling and identification. Unchanged RWJ-51784 (82, 80 & 86% of the sample in rat, dog & human, respectively) plus 6 metabolites were profiled and tentatively identified on the basis of MS data. RWJ-51784 metabolites were formed via the following 3 metabolic pathways: 1. N-demethylation, 2. phenylhydroxylation, and 3. isoindole-oxidation. Pathway 1 produced a moderate or minor metabolite, N-desmethyl-RWJ-51784 (M1; 6% in rat; 5% in dog, 2% in human). Pathway 2 formed 4-hydroxyphenyl-RWJ-51784 (M2; 3-6% in all species). Step 3 formed 2 isoindole-oxidized metaboliotes, OH-indole (M3; 7-8% in all species) and oxo-indole (M4; <1% in all species)-RWJ-51784, and in conjunction with pathway 2 produced 2 trace metabolites, OH-phenyl-OH-isoindole (M5) and OH-phenyl-oxo-isoindole (M6) metabolites. RWJ-51784 is not extensively metabolized in rat, dog and human hepatic S9 fractions.
Descriptors: metabolism, pharmacology, hepatic s9 fraction, culturing techniques, laboratory techniques.



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