Evaluation of the arrhythmogenicity of a low dose of acepromazine: comparison with xylazine.

Alteration in the arrhythmogenic dose of epinephrine (ADE) was determined in 6 healthy dogs under halothane anesthesia following the administration of xylazine at 1.1 mg/kg i.v. and acepromazine at 0.025 mg/kg i.v. The order of treatment was randomly assigned with each dog receiving both treatments and testing was carried out on 2 separate occasions with at least a 1 wk interval. The ADE determinations were made prior to drug administration during halothane anesthesia (CNTL) and then 20 min and 4 h following drug treatment. Epinephrine was infused for 3 min at increasing dose rates (2.5, 5.0, 10.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached within the 3 min of infusion or the 1 min following cessation. The interinfusion interval was 20 min. There was a significant difference (P = 0.0001) in the ADE determined following acepromazine administration at 20 min (20.95 micrograms/kg +/- 2.28 SEM) compared to CNTL (6.64 micrograms/kg +/- 1.09), xylazine at 20 min (5.82 micrograms/kg +/- 0.95) and 4 h (6.13 micrograms/kg +/- 1.05), and acepromazine at 4 h (7.32 micrograms/kg +/- 0.34). No other significant differences existed (P < 0.05). In this study we were unable to show any sensitization to epinephrine following xylazine administration during halothane anesthesia, while a protective effect was shown with a low dose of acepromazine.     

The arrhythmogenic dose of epinephrine in halothane and isoflurane anesthetized dogs: an assessment of repeatability.

Repeat determinations of the arrhythmogenic dose of epinephrine (ADE) were made over two 6 h periods on 2 separate days during halothane and isoflurane anesthesia. Each of 6 dogs underwent 4 trials (2 halothane and 2 isoflurane). During each trial, the ADE was determined at baseline, 3 and 6 h. Epinephrine was infused for 3.0 min at increasing dose rates (2.5, 5.0, 10.0 and 20.0 mg/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The inter-infusion interval was 20 min. There were no significant differences in the measured cardiovascular parameters (SBP, DBP, MBP, and HR), arterial blood gases, or acid-base status prior to each determination during a single trial. The cardiovascular responses to epinephrine infusion were not significantly different between inhalants or determinations. The range of the ADE determined over both trials during isoflurane anesthesia was 30.12 +/- 12.21 micrograms/kg to 50.83 +/- 9.17 micrograms/kg. The baseline ADE during Day 1 of halothane anesthesia (6.70 +/- 1.36 micrograms/kg) was significantly greater than ADE determinations at 3 (4.65 +/- 0.88 micrograms/kg) and 6 h (4.61 +/- 0.87 micrograms/kg). The reduction in the ADE over time during day 2 of halothane anesthesia was not statistically significant (P = 0.0669). These results suggest that during halothane anesthesia, the ADE is not repeatable over time, and they may influence our interpretation of the results of investigations that measure alterations in the ADE due to pharmacological manipulations without repeated control ADE determinations.     

The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs.

The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms.     

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

Alteration in the arrhythmogenic dose of epinephrine (ADE) following xylazine administration to halothane-anesthetized dogs

The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 microgram/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15-sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 +/- 0.522 to 4.17 +/- 0.679 micrograms/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 +/- 4 to 99 +/- 4.9 b.p.m.), and mean arterial pressure significantly increased (83 +/- 4.0 to 122 +/- 3.4 mm Hg). Heart rate measured immediately prior to epinephrine-induced arrhythmia formation was significantly increased following xylazine administration (177 +/- 8 vs 78 +/- 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed alpha agonist, potentiated halothane-induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinephrine infusions.     

Comparison of arrhythmogenic doses of epinephrine in heartworm-infected and noninfected dogs

The arrhythmogenic dose of epinephrine (ADE) was determined in heartworm-infected and noninfected (control) dogs during thiamylal-induced and halothane-maintained anesthesia to assess the myocardial sensitization. The ADE in heartworm-infected dogs (2.42 +/- 0.26 micrograms/kg of body weight) was significantly lower than that for the controls (3.36 +/- 0.29 micrograms/kg). After 2 weeks, ADE was determined again in these dogs after atropine treatment. Atropine treatment lowered the ADE to 1.76 +/- 0.33 micrograms/kg and 1.77 +/- 0.19 micrograms/kg in heartworm-positive and -negative dogs, respectively. After 2 weeks more, the ADE was determined after administration of prazosin, an alpha 1-antagonist. Only 2 of 6 controls and 3 of 6 heartworm-positive dogs had arrhythmias after a threefold increase of ADE. The mean ADE in the dogs that responded to treatment were 7.4 micrograms/kg and 7.2 micrograms/kg for heartworm-positive and -negative dogs, respectively. The finding of this study indicated that ADE in heartworm-infected dogs were lower than those in the control dogs, which makes the heartworm-infected dogs more vulnerable to arrhythmia during anesthesia. Atropine did not protect the dogs of either group. However, prazosin protected the dogs of both groups by significantly increasing the threshold of the ADE. On the basis of our findings, to reduce the risk of arrhythmia, we suggest that routine screening of dogs for heartworm infection be done before anesthetics are used.     

Alterations in epinephrine-induced arrhythmogenesis after xylazine and subsequent yohimbine administration in isoflurane-anesthetized dogs

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% end-tidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.     

Reversal of medetomidine sedation by atipamezole in dogs

Atipamezole reversed the sedative effect of medetomidine in twelve laboratory beagles. The dogs were sedated with medetomidine doses of 20, 40 and 80 micrograms/kg body wt i.m. Atipamezole was injected (i.m.) 20 min later at dose rates two, four, six and ten times higher (in micrograms/kg) than the preceding medetomidine dose. Placebo treatment was included in the study. The deeply sedated dogs showed signs of arousal in 3-7 min and took their first steps 4-12 min after atipamezole injection. The dose-related reversal effect of atipamezole proved to be optimal with doses which were four, six or ten times higher than the preceding medetomidine dose. Drowsiness was found 0.5-1 h after atipamezole injection in 41% of the cases. No adverse effects nor cases of over-alertness or excitement were found.     

Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses.

The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration (MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/kg/min at which at least 4 premature ventricular depolarizations occurred in a 15-second period. Xylazine (1.1 mg/kg, IV) was administered after the control ADE was determined. Xylazine did not significantly alter the ADE (control, 1.12 +/- 0.38 micrograms/kg/min; xylazine, 1.21 +/- 0.46 micrograms/kg/min). Blood pressure increased transiently for 8 minutes after xylazine administration. Baseline systolic and diastolic arterial pressures and heart rate were not significantly different from control baseline pressures and heart rate 15 minutes after xylazine administration. Blood pressure and heart rate increased significantly during control and xylazine ADE determinations. Significant differences in pH, PaO2, PaCO2, or base excess were not observed between baseline and ADE in the control or xylazine groups. One horse developed atrial fibrillation, and 2 horses developed ventricular fibrillation during ADE determinations.     

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.     

Alterations in the arrhythmogenic dose of epinephrine after adrenergic receptor blockade with prazosin, metoprolol, or yohimbine in halothane-xylazine-anesthetized dogs

Recent evidence has linked alpha-receptor and beta-receptor activations with ventricular arrhythmia genesis. In order to assess the relative contribution of specific adrenoceptors (alpha 1, alpha 2, beta 1) on ventricular arrhythmogenic activity during xylazine (1.1 mg X kg-1 X hr-1)-halothane (1.35%) anesthesia, the arrhythmogenic dose of epinephrine (ADE) was repeatedly determined before and after prazosin (alpha 1 antagonist; 0.1 mg X kg-1), metoprolol (beta 1 antagonist; 0.5 mg X kg-1), and yohimbine (alpha 2 antagonist; 0.125 mg X kg-1) administration in 6 dogs. The ADE was expressed as infusion rate and total dose. The ADE was defined as the dose which produced 4 or more intermittent premature ventricular contractions within 15 s during a 3-minute infusion period or within 1 minute from end of infusion. Control ADE was 2.69 +/- 0.372 (micrograms X kg-1 X min-1) and 4.17 +/- 0.544 (micrograms X kg X -1) for infusion rate and total dose, respectively. The ADE significantly increased after prazosin (P less than 0.005), metoprolol (P less than 0.005), and yohimbine (P less than 0.05) administration. The ADE values increased to 5.42 +/- 1.22 (rate) and 8.10 +/- 1.95 (dose) after alpha 2 blockade, but were significantly less than the alpha 1 and beta 1 blockade ADE values. In conclusion, although both alpha- and beta-adrenoceptor blockade depressed ventricular arrhythmia genesis in xylazine-halothane-anesthetized dogs, alpha 2 blockade, which was achieved with the recommended dose of yohimbine for reversal of anesthetic-induced CNS depression, was not as protective as alpha 1 (prazosin) or beta 1 (metoprolol) blockade.     

Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs

OBJECTIVE: To determine sedative and cardiorespiratory effects of i.m. administration of medetomidine alone and in combination with butorphanol or ketamine in dogs. DESIGN: Randomized, crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs were given medetomidine alone (30 micrograms/kg [13.6 micrograms/lb] of body weight, i.m.), a combination of medetomidine (30 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or a combination of medetomidine (30 micrograms/kg, i.m.) and ketamine (3 mg/kg [1.36 mg/lb], i.m.). Treatments were administered in random order with a minimum of 1 week between treatments. Glycopyrrolate was given at the same time. Atipamezole (150 micrograms/kg [68 micrograms/lb], i.m.) was given 40 minutes after administration of medetomidine. RESULTS: All but 1 dog (given medetomidine alone) assumed lateral recumbency within 6 minutes after drug administration. Endotracheal intubation was significantly more difficult when dogs were given medetomidine alone than when given medetomidine and butorphanol. At all evaluation times, percentages of dogs with positive responses to tail clamping or to needle pricks in the cervical region, shoulder region, abdominal region, or hindquarters were not significantly different among drug treatments. The Paco2 was significantly higher and the arterial pH and Pao2 were significantly lower when dogs were given medetomidine and butorphanol or medetomidine and ketamine than when they were given medetomidine alone. Recovery quality following atipamezole administration was unsatisfactory in 1 dog when given medetomidine and ketamine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of medetomidine with butorphanol or ketamine resulted in more reliable and uniform sedation in dogs than did medetomidine alone.     

The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog

The efficacy of atipamezole, a recently introduced alpha 2-adrenoceptor antagonist, in reversing medetomidine-induced effects in dogs was investigated in a clinical study. Dogs from eight Finnish small-animal hospitals were sedated with a 40-microgram/kg dose of the alpha 2-agonist medetomidine i.m. In the first part of the study (n = 319), a randomized, double-blind design with respect to the dose of atipamezole (0, 80, 160 and 240 micrograms/kg i.m.) was used. In a separate study (n = 358), which was an open trial, the selected dose of atipamezole was 200 micrograms/kg i.m. Atipamezole at dose rates of 80-240 micrograms/kg rapidly and effectively reversed medetomidine-induced deep sedation-analgesia, recumbency and bradycardia. The median arousal time after atipamezole was 3-5 min, and walking time was 6-10 min compared to greater than 30 min for both effects after placebo. Heart rate also increased in a dose-related manner after atipamezole administration. The investigators' overall evaluation of the ability of atipamezole to reverse the effects of medetomidine was 'good' in 90%, and 'moderate' in 9% of cases. Relapse into sedation was reported in three individual cases. Side-effects were minimal. It is concluded that at doses four- to sixfold the medetomidine dose, atipamezole is a highly effective and safe agent in reversing medetomidine-induced sedation-analgesia, recumbency and bradycardia in dogs in veterinary practice.     

Effects of Xylazine and Ketamine on Epinephrine-lnduced Arrhythmia in the Dog

Ten dogs were studied to determine the effects of xylazine, ketamine, and xylazine combined with ketamine on the dosage of epinephrine required to produce ventricular arrhythmia. Untreated dogs required an arrhythmogenic dose (AD) of 5.88 +/- 2.85 micrograms/kg/min. The AD was 4.28 +/- 3.25 micrograms/kg/min in xylazine-treated dogs, 3.05 +/- 2.3 micrograms/kg/min in ketamine-treated dogs, and 2.96 +/- 1.95 micrograms/kg/min in xylazine/ketamine-treated dogs. The latter two dosages were significantly less than that of the controls (p less than 0.025). The duration of increased arrhythmogenicity was also examined. Four hours after drug administration, the AD for xylazine-treated dogs was decreased further to 3.87 +/- 2.52 micrograms/kg/min (p less than 0.05). Ketamine-treated dogs had returned partially to normal with an AD of 4.09 +/- 3.09 micrograms/kg/min, as had xylazine/ketamine-treated dogs, at 4.22 +/- 2.71 micrograms/kg/min.     

Ketamine and the arrhythmogenic dose of epinephrine in cats anesthetized with halothane and isoflurane

Epinephrine-induced arrhythmias were studied in 4 cats (group A), using a 4 X 4 Latin square design. Each cat was anesthetized 4 times, 1 week apart, with halothane (1.5% end expired), isoflurane (2.0% end expired), and halothane or isoflurane preceded by ketamine administered IM (8.8 mg/kg). Lead II of the ECG and femoral artery pressure were recorded. Epinephrine was infused in progressively doubled rates (initial rate = 0.125 micrograms/kg/min) for a maximum of 2.5 minutes or until at least 4 ventricular premature depolarizations occurred within 15 s of each other. The arrhythmogenic dose of epinephrine (ADE; micrograms/kg) was calculated as the product of infusion rate and time to arrhythmia. The ADE (means +/- SD) during anesthesia with halothane alone and with ketamine-halothane anesthesia were 1.33 +/- 0.65 and 1.37 +/- 0.59 micrograms/kg, respectively; during anesthesia with isoflurane alone and ketamine-isoflurane anesthesia, the ADE were 9.34 +/- 1.29 and 16.16 +/- 3.63 micrograms/kg, respectively. The ADE was significantly greater (P less than 0.05) during isoflurane anesthesia and ketamine-isoflurane anesthesia than during halothane anesthesia. The percentages of change in systolic blood pressure (means +/- SD) at the ADE during halothane, ketamine-halothane, isoflurane, and ketamine-isoflurane were 31 +/- 34, 41 +/- 17, 127 +/- 27, and 148 +/- 57, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of nifedipine on xylazine-induced acute pressor response in halothane-anesthetized dogs

Effects and interaction of nifedipine (Ca channel blocker) and xylazine (mixed alpha agonist) during halothane anesthesia were examined in 6 dogs. After achievement of steady-state halothane (1.35%) anesthesia, blood pressure (BP) and heart rate (HR) were recorded in these dogs during 3-minute saline or nifedipine (20 micrograms/kg) infusion periods. Seven minutes after the end of saline or nifedipine infusion, xylazine (1.1 mg/kg of body weight) was infused over a 2-minute period. After saline pretreatment, xylazine administration increased diastolic BP (33.67 +/- 3.91 mm of Hg) and decreased HR. Nifedipine infusion induced a transient reduction in BP, accompanied by a more persistent increase in HR. Compared with saline pretreatment, nifedipine pretreatment significantly decreased the acute increase in diastolic BP (33.67 +/- 3.91 vs 14.00 +/- 2.94 mm of Hg) which occurred during xylazine injection. After saline and nifedipine infusions, xylazine administration decreased HR 30 +/- 15.02 and 36.5 +/- 10.36 beats/min, respectively. A pronounced sinus arrhythmia and/or 2nd-degree atrioventricular block developed in all dogs during xylazine injection after saline infusion. Arrhythmias were not observed in the dogs after nifedipine infusion. Nifedipine's Ca blocking action depressed xylazine-induced acute vasoconstriction and concomitant increase in diastolic BP. Because alpha 2-, but not alpha 1-adrenoceptor-mediated vasoconstriction is Ca-dependent, these results indicate that a portion of the acute pressor response induced by IV xylazine in halothane-anesthetized dogs may be alpha 2-mediated. Seemingly, nifedipine-induced hypotension and damping of xylazine-induced increases in BP attenuated xylazine's actions on cardiac rate and rhythm.     

Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats

OBJECTIVE: To evaluate the effects of medetomidine and its antagonism with atipamezole in goats. STUDY DESIGN: Prospective randomized crossover study with 1 week between treatments. ANIMALS: Six healthy 3-year-old neutered goats (three male and three female) weighing 39.1-90.9 kg (60.0 +/- 18 kg, mean +/- SD). METHODS: Goats were given medetomidine (20 microg kg(-1), IV) followed, 25 minutes later, by either atipamezole (100 microg kg(-1), IV) or saline. Heart and respiratory rate, rectal temperature, indirect blood pressure, and mechanical threshold were measured, and sedation and posture were scored and blood samples obtained to measure epinephrine, norepinephrine, free fatty acids, glucose, and cortisol concentrations at baseline (immediately before medetomidine), 5 and 25 minutes after medetomidine administration, and at 5, 30, 60, and 120 minutes after the administration of antagonist or saline. Parametric and nonparametric tests were used to evaluate data; p < 0.05 was considered significant. RESULTS: Medetomidine decreased body temperature, heart rate, and respiratory rate and increased mean arterial blood pressure, cortisol, and glucose. Recumbency occurred 89 +/- 50 seconds after medetomidine administration. All goats were standing 86 +/- 24 seconds after atipamezole administration whereas all goats administered saline were sedate and recumbent at 2 hours. Tolerance to compression of the withers and metacarpus increased with medetomidine. From 5 to 120 minutes after saline or atipamezole administration, there were differences in body temperature, glucose, and cortisol but none in heart rate or blood pressure. Three of the six goats receiving saline developed bloat; five of six urinated. After atipamezole, four of six goats developed piloerection and all goats were agitated and vocalized. CONCLUSION: At the doses used, atipamezole antagonized the effects of medetomidine on recumbency, sedation, mechanical threshold, and the increase in glucose. Atipamezole increased the rate of return of cortisol toward baseline, and prevented further decline in rectal body temperature. CLINICAL RELEVANCE: Atipamezole may be used to antagonize some, but not all effects of medetomidine.     

The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs

This study aimed to compare the antagonistic effects of atipamezole (40, 120, and 320 μg/kg, IM), yohimbine (110 μg/kg, IM), and saline on neurohormonal and metabolic responses induced by medetomidine (20 μg/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.     

Effects of the opioid remifentanil on the arrhythmogenicity of epinephrine in halothane-anesthetized dogs

Opioids may exert a protective effect against ventricular arrhythmias via a vagally mediated mechanism. This study evaluated the effects of the opioid remifentanil on arrhythmogenicity of epinephrine during halothane anesthesia. Eight dogs were assigned to 2 treatments in a randomized crossover design, with 1-week intervals between treatments. Anesthesia was maintained with 1.3% end-tidal halothane in oxygen and mechanical ventilation to maintain eucapnia. A constant rate infusion of remifentanil (0.72 microg/kg/min) was administered throughout the study in the experimental treatment, while control animals received physiologic saline as placebo. The arrhythmogenic dose of epinephrine (ADE), defined as 4 premature ventricular complexes (PVCs) within 15 s, was determined by administering progressively increasing infusion rates of epinephrine (2.5, 5.0, and 10 microg/kg/min), allowing 20 min intervals between each infusion rate. In both treatments, epinephrine infusions induced bradyarrhythmias and atrioventricular conduction disturbances, which were followed by escape beats and PVCs. In the remifentanil treatment, mean +/- s ADE values (11.3 +/- 4.9 microg/kg) did not differ from values observed in control animals (9.9 +/- 6.1 microg/kg). On the basis of the ADE model for assessing the arrhythmogenity of drugs during halothane anesthesia, the present study did not demonstrate a protective effect of remifentanil (0.72 microg/kg/min) against ventricular arrhythmias in dogs.     

The effect of medetomidine premedication upon propofol induction and infusion anaesthesia in the dog

The effect of premedication with four different intramuscular doses of medetomidine (5.0,10.0, 20.0 and 40.0 μg.kg-¹) and a saline placebo were compared in a group of six adult beagle dogs anaesthetised with propofol on five separate occasions. Anaesthesia was induced 30 minutes after premedication and maintained by intravenous injection and continuous infusion of propofol. The effects of medetomidine were reversed with atipamezole 30 minutes after anaesthetic induction. The marked synergistic effects of medetomidine with propofol were demonstrated by a dose related reduction in the induction and infusion requirements for a similar degree of anaesthesia. The effect appeared exponential in nature; lower medetomidine doses produced a disproportionately greater effect.
The maintenance of anaesthesia with propofol following a saline placebo or low doses of medetomidine proved to be difficult. Higher doses of medetomidine required less propofol for induction and infusion and allowed a more stable anaesthesia to be maintained. Propofol produced no statistically significant change in heart rate during infusion. Changes in respiratory rate were markedly group specific. A significant reduction in respiratory rate was seen in dogs given either 5 μg.kg- or 10 μ-g.kg-¹ medetomidine. No change was recorded in dogs given 20 /μg.kg-¹ medetomidine and a significant increase was seen in dogs given 40 μg.kg-¹ medetomidine. Recovery was monitored following the termination of propofol infusion after the reversal of medetomidine using atipamezole at five times the medetomidine dose. Recovery was slower for dogs given lower doses of medetomidine and consequently higher doses of propofol.