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.     

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.     

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)     

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.     

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.     

Halothane-catecholamine arrhythmias in swine (Sus scrofa)

The arrhythmogenic dose of epinephrine (ADE) was determined in 6 pigs during steady-state anesthesia (1.5% halothane in O2) and steady-state anesthesia plus xylazine (1.1 mg X kg-1 X hr-1; IV infusion) and after either prazosin (alpha 1) or metoprolol (beta 1) adrenergic blockade during halothane-xylazine (H-X) anesthesia. A constant infusion (1, 2, 3, 5, and 10 micrograms X kg-1 X min-1) of freshly mixed epinephrine (100 micrograms X ml-1 in saline solution) was used to determine ADE. The ADE was defined as the total dose of epinephrine which produced 4 or more continuous or intermittent, premature, ventricular contractions within a 15-s period. The mean epinephrine total dose values during 1.5% halothane anesthesia, H-X anesthesia alone, or H-X anesthesia after either prazosin (0.1 mg X kg-1) or metoprolol (0.5 mg X kg-1) adrenergic blockade were 3.60 +/- 0.844, 2.68 +/- 0.402, 11.85 +/- 3.804, and 5.17 +/- 0.587 micrograms X kg-1, respectively. Xylazine administration did not significantly decrease ADE, although mean arterial pressure significantly increased. Prazosin administration significantly increased ADE and was associated with an increased heart rate and a decreased mean arterial pressure. We conclude that alpha 1-blockade with prazosin is more protective to epinephrine-induced arrhythmias in H-X-anesthetized pigs than is beta 1-blockade with metoprolol.     

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.     

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.     

Ventricular arrhythmogenic dose of epinephrine in dogs and cats anesthetized with tiletamine/zolazepam and halothane

The ventricular arrhythmogenic dose of epinephrine (ADE) was determined in 6 dogs anesthetized with halothane alone or with halothane after injection of tiletamine/zolazepam (TZ). Respiratory rate and tidal volume were controlled and sodium bicarbonate was administered to maintain arterial pH and blood gas values within reference range. Heart rate and arterial blood pressure were recorded during determination of the ADE. The ADE (mean +/- SD) was no different during anesthesia with use of halothane alone (8.9 +/- 4.3) than it was when injections of TZ preceded administration of halothane (6.7 +/- 2.8). Tiletamine/zolazepam was also administered IV immediately after determination of the ADE during halothane-induced anesthesia. The TZ administered in this manner did not alter the ADE. Blood pressure and heart rate were significantly greater during infusion of epinephrine than immediately prior to infusion. The administration of TZ did not alter blood pressure response. The ADE was also determined in 6 cats anesthetized with halothane preceded by administration of TZ. The ADE (mean +/- SD) was 0.7 +/- 0.23 micrograms/kg, a value similar to that reported for cats during anesthesia with halothane alone.     

Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.     

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.     

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.     

Xylazine and tiletamine-zolazepam anesthesia in horses

The cardiopulmonary and anesthetic effects of xylazine in combination with a 1:1 mixture of tiletamine and zolazepam were determined in 6 horses. Each horse was given xylazine IV or IM, as well as tiletamine-zolazepam IV on 4 randomized occasions. Anesthetics were administered at the rate of 1.1 mg of xylazine/kg of body weight, IV, 1.1 mg of tiletamine-zolazepam/kg, IV (treatment 1); 1.1 mg of xylazine/kg, IV, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 2); 1.1 mg of xylazine/kg, IV, 2.2 mg of tiletamine-zolazepam/kg, IV (treatment 3); and 2.2 mg of xylazine/kg, IM, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 4). Tiletamine-zolazepam doses were the sum of tiletamine plus zolazepam. Xylazine, when given IV, was given 5 minutes before tiletamine-zolazepam. Xylazine, when given IM, was given 10 minutes before tiletamine-zolazepam. Tiletamine-zolazepam induced recumbency in all horses. Duration of recumbency in group 1 was 31.9 +/- 7.2 (mean +/- 1 SD) minutes. Increasing the dosage of tiletamine-zolazepam (treatments 2 and 3) significantly (P less than 0.05) increased the duration of recumbency. Xylazine caused significant (P less than 0.05) decreases in heart rate and cardiac output and significant (P less than 0.05) increases in central venous pressure and mean pulmonary artery pressure 5 minutes after administration. Respiratory rate was decreased. Arterial blood pressures increased significantly (P less than 0.05) after xylazine was administered IV in treatments 1 and 3, but the increases were not significant in treatment 2. Xylazine administered IM caused significant (P less than 0.05) increases in central venous pressure and significant (P less than 0.05) decreases in cardiac output.(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.     

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine.     

Cardiopulmonary effects of intramuscular xylazine-ketamine in calves.

The cardiopulmonary effects of an intramuscular xylazine (0.088 mg/kg)-ketamine (4.4 mg/kg) drug combination were evaluated in calves. Heart rate, central venous and mean pulmonary artery blood pressures, and cardiac output did not change after drug administration. Mean arterial blood pressure decreased significantly (P less than 0.05) 15 minutes after drug administration. Respiratory frequency increased significantly (P less than 0.05) whereas arterial partial pressure of oxygen (PaO2) decreased significantly (P less than 0.05) after drug administration. The duration of lateral recumbency was 55.7 +/- 10.4 minutes. Immediate or long-term adverse effects were not observed.     

Influence of Cholinergic Blockade on the Development of Epinephrine-Induced Ventricular Arrhythmias in Halothane- and Isoflurane-Anesthetized Dogs

The arrhythmogenic effects of anesthetic drugs are assessed using the arrhythmogenic dose of epinephrine (ADE) model. The purpose of this study was to determine the influence of cholinergic blockade (CB) produced by glycopyrrolate (G) on ADE in 1.5 minimum alveolar concentration (MAC) halothane (H)- and isoflurane (I)-anesthetized dogs. Eight dogs (weighing between 12.5 and 21.5 kg) were randomly assigned to four treatment groups (H, HG, I, and IG) and each treatment was replicated three times. Anesthesia was induced and maintained with H (1.31%, end-tidal [ET]) or I (1.95%, ET) in oxygen. Ventilation was controlled (carbon dioxide [PCO₂] 35 to 40 mmHg, ET). G was administered 10 minutes before ADE determination at a dose of 22 μg/kg (11 μg/kg, intravenous [IV] and 11 μg/kg, intramuscular [IM]). The ADE was determined by IV infusion of epinephrine at sequentially increasing rates of 1.0, 2.5, and 5.0 μg/kg/min; and defined as the total dose of epinephrine producing at least four ectopic ventricular contractions (EVCs) within 15 seconds during a 3-minute infusion and up to 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Data were analyzed using a randomized complete block analysis of variance. When significant (P < .05) F values were found a least significant difference test was used to compare group means. Values are reported as means ± standard error. The ADE (μg/kg) for H, HG, I, and IG were 1.53 ± 0.08, 3.37 ± 0.46, 1.61 ± 0.21, and > 15.00, respectively. Heart rates (HRs) (beats/min) and systolic pressures (mmHg) at the time of arrhythmia formation for H, HG, I, and IG were (60.3 ±4.0 and 142.0 ± 7.6), (213.0 ± 13.1 and 239.2 ± 7.1), (62.9 ± 4.5 and 151.9 ± 6.3), and (226.3 ± 6.1 and 323.5 ± 3.4), respectively. The H and I ADE were not different. The HG ADE was significantly less than the IG ADE. The H and I ADE were significantly less than the HG and IG ADE. We conclude the following from the results of this study of epinephrine infusion in halothane- and isoflurane-anesthetized dogs: (1) two distinct mechanisms are responsible for the development of arrhythmias, (2) CB produced by G significantly increases ADE but is associated with higher rate pressure products (RPP) and myocardial work, and (3) ADE methodology could be improved by determining ADE with and without CB.     

A balanced anesthesia with a combination of xylazine, ketamine and butorphanol and its antagonism by yohimbine in pigs.

The effects of intramuscular injections of xylazine (2 mg/kg)-ketamine (15 mg/kg) [X-K15], and xylazine (2 mg/kg)-ketamine (5 mg/kg)-butorphanol (0.22 mg/kg) [X-K5-B] were compared in atropinized (0.05 mg/kg) miniature pigs (pigs). Both combinations induced the anesthesia for more than 1 hr, however X-K5-B induced the more potent and well balanced anesthesia as compared with X-K15, although the amount of ketamine was reduced to one third. The duration of loss of pedal reflex, an indicator of surgical anesthesia, in X-K5-B (62 +/- 13 min) was significantly (P less than 0.05) longer than in X-K15 (28 +/- 19 min). In addition, X-K5-B was accompanied by loss of laryngeal reflex in all pigs. Recovery from anesthesia in X-K5-B was much smoother than in X-K15, and the administration of yohimbine (0.05 mg/kg) could rapidly and smoothly reverse the anesthesia induced by X-K5-B, although it was accompanied by a transient fall in blood pressure and tachycardia. The combination of xylazine, ketamine and butorphanol appears to be a relatively safe and widely available anesthesia for the period of one hour in pigs.     

Cardiopulmonary effects of xylazine and yohimbine in laterally recumbent sheep.

The effects of yohimbine (0.125 mg/kg) on cardiopulmonary parameters in six adult, xylazine treated (0.15 mg/kg), laterally recumbent sheep were studied. Following collection of baseline data, xylazine was administered intravenously and data were collected five and fifteen minutes later. At twenty minutes post-xylazine either yohimbine (0.125 mg/kg) or saline was given and further collection of data occurred at 25, 30, 40 and 50 minutes. Xylazine administration resulted in significant (P less than 0.05) respiratory depression, as reflected by a decrease in arterial oxygen partial pressure (PaO2). No significant changes in haemodynamic variables were observed. Yohimbine produced a significant improvement in PaO2 at the 50 minute period and abolished the paradoxical respiratory pattern when present. The results indicated that yohimbine can be used as an antagonist to control the duration of xylazine induced respiratory depression, although the degree of reversal was less than is clinically desirable.     

Cardiovascular effects of vasopressors in isoflurane-anesthetized dogs before and after hemorrhage

Exogenously administered vasopressors (sympathomimetics) were evaluated in isoflurane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and isoflurane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure, heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Before hemorrhage, administration of high doses of dobutamine and medium and high doses of epinephrine were equally effective at increasing CI and SI. The dP/dT was increased to the greatest degree by administration of high doses of dobutamine. Administration of the low dose of dobutamine increased dP/dT, whereas administration of the low dose of epinephrine increased CI, HR, and SI, and decreased SVR. The HR and SVR were not increased by administration of any dose of dobutamine or of the medium and high doses of epinephrine. However, methoxamine increased SVR and decreased HR. Methoxamine decreased CI, SI, and dP/dT, but increased systemic arterial pressure to the same degree as that attributed to administration of high doses of dobutamine and epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)