Antagonism of xylazine sedation with yohimbine, 4-aminopyridine, and doxapram in dogs

Groups of atropinized dogs (6 dogs/group) were sedated with xylazine (2.2 mg/kg of body weight, IM). At recumbency, the dogs were given IV saline solution (control groups), yohimbine (0.05, 0.1, and 0.2 mg/kg), 4-aminopyridine (4-AP; 0.3, 0.6, and 0.9 mg/kg), doxapram (0.5, 1.0, 2.0, and 4.0 mg/kg), or the smallest dose of these antagonists in dual combinations or in triple combination. Two additional groups were sedated with an overdose of xylazine (11 mg/kg, IM). At recumbency, 1 of these groups was given saline solution IV and the other group was given yohimbine IV (0.4 mg/kg) as the antagonist. With the 2.2 mg/kg dose of xylazine, control mean arousal time (MAT) and mean walk time (MWT) were 15.5 minutes and 24.8 minutes, respectively. These values were decreased by the individual antagonists to 0.5 to 2.5 minutes and 0.9 to 7.4 minutes, respectively. Approximate equipotent doses of antagonists (mg/kg) were: yohimbine, 0.2; 4-AP, 0.6; and doxapram, 0.5. Relapses did not occur after yohimbine or 4-AP. With doxapram, muscle tremors and spasms, abnormal postures, or aggressive behavior occurred in several dogs and several dogs had partial or complete relapses. The small doses of individual antagonists were synergistic with regard to MAT, MWT, and duration of residual sedation, but the various combinations of antagonists were not more effective in these regards than were larger doses of the single antagonists. With the overdose of xylazine, control MAT and MWT were 41.5 minutes and 144.5 minutes, respectively. Yohimbine decreased these values to 2.2 minutes and 2.5 minutes, respectively. Relapses did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Halothane-sparing effect of xylazine in dogs and subsequent reversal with tolazoline

Halothane MAC (the minimum alveolar concentration of halothane to produce anaesthesia in 50% of the animals tested) was determined to be 0.92 ± 0.16 volumes % in eight English Pointer dogs. Alterations in halothane MAC induced by an intravenous bolus of xylazine (1.1 mg/kg) and then tolazoline (5 mg/kg) was determined in each dog following control (halothane MAC) measurement. Following xylazine administration, MAC significantly decreased to 0.57 ± 0.023%. Immediately following determination of the xylazine-halothane MAC value in each dog, tolazoline was administered and the halothane requirement (MAC) was again assessed. Halothane MAC significantly increased to 1.24 ± 0.036%. Tolazoline administration induced immediate arousal in the xylazine-halothane anaesthetized dogs requiring a rapid increase in halothane concentration to maintain anaesthesia. Thus, the administration of tolazoline, an alpha adrenergic antagonist, following xylazine administration significantly increased the anaesthetic requirement (MAC) of halothane. Xylazine, an alpha 2 adrenergic agonist, decreased halothane anaesthetic requirement (MAC) in the eight dogs studied. These results are consistent with the hypotheses that stimulation of central alpha 2 receptors is the mechanism by which xylazine produces sedation and that inhibition of CNS excitatory neurotransmitter release decreases halothane anaesthetic requirement. In contrast, the increase in halothane requirement and arousal from xylazine-halothane anaesthesia that occurred following i.v. tolazoline administration indicates an increase in CNS excitatory neurotransmitter activity.     

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)     

Atrial fibrillation in halothane- and isoflurane-anesthetized dogs

Programmed electrical stimulation techniques were used to evaluate the effects of halothane and isoflurane on induction of atrial fibrillation in anesthetized dogs. Experiments were performed in 16 dogs anesthetized with alpha-chloralose. Critically timed premature stimuli were applied to the right atrial appendage and Bachmann bundle to determine the atrial fibrillation threshold, defined as the minimal current required to induce rapid, irregular atrial electrical activity of at least 8 seconds' duration. Atrial fibrillation thresholds were determined at baseline (0.0% inhalational anesthetic), 0.5 minimal alveolar concentration (MAC), and 1.0 MAC of halothane (n = 8) and isoflurane (n = 8). In the absence of inhalation anesthetic, it was significantly (P less than 0.01) easier to induce atrial fibrillation at the Bachmann bundle vs the right atrial appendage. Atrial fibrillation threshold at the Bachmann bundle was not affected by increasing concentrations of halothane, but was increased by 1.0 MAC of isoflurane (P less than 0.05). It was concluded that at 1.0 MAC isoflurane, but not halothane, has antifibrillatory effects in atrial tissue.     

Cardiac performance in cats after administration of xylazine or xylazine and glycopyrrolate: echocardiographic evaluations

Cardiac performance was evaluated in 9 healthy cats sedated with xylazine. Each cat was evaluated echocardiographically before and after the administration of xylazine or xylazine and glycopyrrolate. Each cat was echocardiographically evaluated during manual restraint only (control value), after IM administration of 0.55 mg of xylazine/kg of body weight, after IM administration of 2.2 mg of xylazine/kg, and after IM administration of 0.011 mg of glycopyrrolate/kg followed 10 minutes later by IM administration of 2.2 mg of xylazine/kg. Echocardiographic indices of cardiac performance (fractional shortening, left ventricular wall amplitude, aortic amplitude, mitral valve E point septal separation) indicated a significant decrease (P less than 0.05) in the left ventricular function and heart rate after the small (0.55 mg/kg) and large (2.2 mg/kg) dosages of xylazine. With the administration of glycopyrrolate, the bradycardia was minimized, but cardiac performance was not improved. After administration of glycopyrrolate, cardiac performance decreased, but the decrease was not significant when compared with the ventricular performance of the cats after administration of the large dosage of xylazine. Compared with control values, the reduction in left ventricular function values associated with administration of xylazine or xylazine and glycopyrrolate was independent of the heart rate. Therefore, the alpha-2 adrenergic agonist xylazine has a marked depressive effect on cardiac performance in the cat, and premedication with glycopyrrolate may not completely alleviate the undesirable bradycardia, but may actually be detrimental to the cardiovascular system.     

Antagonism of xylazine sedation by 4-aminopyridine and yohimbine in cattle

Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0.2 to 0.3 mg/kg of body weight). When the steers were maximally sedated, group I (control group) were given isotonic saline solution (1 ml, IV), group II were given 4-aminopyridine (4-AP, 0.3 mg/kg) IV, group III were given yohimbine hydrochloride (0.125 mg/kg) IV, and group IV were given 4-AP (0.3 mg/kg) plus yohimbine hydrochloride (0.125 mg/kg) IV. The 4-AP decreased mean standing time (MST; time until animal could stand unaided) from 94.3 minutes (control) to 13.4 minutes. Yohimbine decreased MST to 27 minutes. The combination of 4-AP + yohimbine decreased MST to 7.4 minutes. Mean total recovery time (MTRT; time from xylazine injection until normal behavior, including eating and drinking) was not significantly (P = greater than 0.05) decreased from control values by any of the antagonists tested. The combination of 4-AP + yohimbine decreased MST in animals given a 3X overdose of xylazine (0.6 mg/kg) from 124 minutes (control) to 30.3 min. The MTRT was not significantly (P greater than 0.05) decreased from control values. Two animals given a 5X overdose of xylazine (1 mg/kg) and then given 4-AP + yohimbine had a MST of 32.5 minutes and a MTRT of 3.7 hours. The combination of 4-AP + yohimbine produced marked antagonism of xylazine sedation in cattle. The combination of antagonists may prove to be useful for the arousal of animals sedated with xylazine alone or with a combination of sedatives including xylazine.     

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.     

Reversal of thiopental-induced anesthesia by 4-aminopyridine, yohimbine, and doxapram in dogs pretreated with xylazine or acepromazine

Groups of atropinized dogs (6 dogs/group) were sedated, using xylazine HCl (2.2 mg/kg of body weight, IM) or acepromazine maleate (0.25 mg/kg, IM), and were anesthetized to loss of pedal reflexes, using thiopental, IV. The dogs were given 1 of the following test antagonists, IV: saline solution (2 ml; control group), 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), doxapram (5.0 mg/kg), or dual combinations of the latter 3 substances in the same doses as used for each agent. In xylazine-treated dogs, the mean dosage of thiopental required to induce anesthesia was 4.8 mg/kg. Control mean arousal time (MAT) and walk time (MWT) were 37.1 minutes and 53.8 minutes, respectively. These values were decreased to less than 2 minutes and less than 3 minutes, respectively, by yohimbine, 4-AP + yohimbine, and doxapram + yohimbine. With doxapram and with 4-AP + doxapram, MAT was less than 2 minutes and MWT was less than 8 minutes. In acepromazine-treated dogs, the mean dosage of thiopental required for anesthesia was 15.0 mg/kg. Control MAT and MWT were 20.7 minutes and 36.5 minutes, respectively. These values were decreased to 8.1 minutes and 18.1 minutes, respectively, by doxapram, and to 3.5 minutes and 19.9 minutes, respectively, by doxapram + yohimbine. Doxapram, 4-AP + doxapram, and doxapram + yohimbine caused periodic extensor rigidity before and during arousal. This rigidity was accompanied by opisthotonos in 2 dogs of the doxapram + yohimbine group and may have been mild tonic seizures.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Pharmacokinetics of ketamine and its metabolite, norketamine, after intravenous administration of a bolus of ketamine to isoflurane-anesthetized dogs

OBJECTIVE: To determine the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized dogs. Animals-6 dogs. PROCEDURE: The minimum alveolar concentration (MAC) of isoflurane was determined in each dog. Isoflurane concentration was then set at 0.75 times the individual's MAC, and ketamine (3 mg/kg) was administered IV. Blood samples were collected at various times following ketamine administration. Blood was immediately centrifuged, and the plasma separated and frozen until analyzed. Ketamine and norketamine concentrations were measured in the plasma samples by use of liquid chromatography-mass spectrometry. Ketamine concentration-time data were fitted to compartment models. Norketamine concentration-time data were examined by use of noncompartmental analysis. RESULTS: The MAC of isoflurane was 1.43 +/- 0.18% (mean +/- SD). A 2-compartment model best described the disposition of ketamine. The apparent volume of distribution of the central compartment, the apparent volume of distribution at steady state, and the clearance were 371.3 +/- 162 mL/kg, 4,060.3 +/- 2,405.7 mL/kg, and 58.2 +/- 17.3 mL/min/kg, respectively. Norketamine rapidly appeared in plasma following ketamine administration and had a terminal half-life of 63.6 +/- 23.9 minutes. A large variability in plasma concentrations, and therefore pharmacokinetic parameters, was observed among dogs for ketamine and norketamine. CONCLUSIONS AND CLINICAL RELEVANCE: In isofluraneanesthetized dogs, a high variability in the disposition of ketamine appears to exist among individuals. The disposition of ketamine may be difficult to predict in clinical patients.     

Prolonged depression of thermoregulation after xylazine administration to cats

Xylazine administered subcutaneously (s.c.; 1–4 mg/kg) or intravenously (i.v.; 0.5-2 mg/kg) to cats consistently caused dose-related decreases in body temperature which were maximal 3–4 h after injection and lasted for at least 12 h. Otherwise the animals appeared to have recovered fully from the central nervous system effects of the drug within 1.5–3.5 h. Xylazine-induced hypothermia developed more rapidly in cats placed in a 4°C environment and, in contrast, was replaced by a hyperthermic response in cats placed in a 32°C environment. These changes in body temperature were not opposed by compensatory thermoregulatory effector activity such as shivering or tachypnea. This pattern of responses at varied environmental temperatures is indicative of a general depression of the thermo-regulation. Thus, animals given xylazine should not be exposed to extreme heat or cold for several hours to avoid development of hyper- or hypothermia.     

Antagonism of xylazine and ketamine anesthesia by 4-aminopyridine and yohimbine in geldings

Thirty-six fasted, mixed horse breed geldings (6 groups of 6 animals each) were anesthetized with xylazine and ketamine, and when maximally sedated, were given 1 of the following antagonists: saline solution, 4-aminopyridine (4-AP), small-dose yohimbine, large-dose yohimbine, 4-AP plus low-dose yohimbine, or 4-AP plus high-dose yohimbine. Measured data included mean standing time (MST), heart rate, respiratory rate, rectal temperature, and mean total recovery time ( MTRT ). Emergence phenomena were also observed and recorded as smooth, fairly smooth, fairly rough, or rough. Groups given 4-AP alone, small-dose yohimbine alone, or large-dose yohimbine alone produced a significant (P less than 0.05) decrease in MST (9.9 +/- 1.6 minutes, 11.3 +/- 1.7 minutes, and 10.6 +/- 2.3 minutes, respectively) compared with that in the saline control group (24.3 +/- 9.2 minutes). The MTRT were not significantly (P greater than 0.05) different (47.2 +/- 10 minutes, 90.4 +/- 15.1 minutes, and 83.2 +/- 23 minutes, respectively) from control values (66.2 +/- 13.4 minutes). When the antagonists were combined, 4-AP plus small-dose yohimbine and 4-AP plus large-dose yohimbine produced significant (P less than 0.05) decreases (10.3 +/- 2 minutes and 8.3 +/- 2.6 minutes, respectively) in MST compared with that of saline controls. The MTRT was significantly longer in the combined antagonist group (4-AP + small-dose yohimbine--131.8 +/- 28.9 minutes; 4-AP + large-dose yohimbine--131.3 +/- 19.4 minutes) compared with that of control or any antagonist alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats

Yohimbine, 4-aminopyridine, and a combination of the 2 drugs were studied to assess their potential as antagonists to xylazine in goats. Twenty-four small East African goats were divided randomly into 4 groups of 6 goats each in a placebo-controlled study. They were all treated with intramuscular xylazine at 0.44 mg/kg. At the time of maximum sedation, sterile water was administered intravenously to the control group, 0.15% 4-aminopyridine at 0.4mg/kg to Group 2, 0.1% yohimbine at 0.25 mg/kg to Group 3, and the combination of the 2 drugs at the same dose rates to Group 4. The yohimbine/4-aminopyridine combination was also used to antagonise xylazine at 0.88mg/kg in 6 goats. The heart rate, respiratory rate and rate of ruminal movements, the pedal and palpebral reflexes as well as the reaction to noxious stimuli, the standing time and the total recovery time were established and evaluated to assess the effects of the treatments. The drugs reversed the xylazine-induced decrease in the heart rate, respiratory rate and rate of ruminal movements, and also rapidly restored the reflexes as well as the reaction to noxious stimulation. In addition, they significantly (P < 0.05) decreased the mean standing time. The mean total recovery time was decreased significantly (P < 0.05) by 4-aminopyridine and the yohimbine/4-aminopyridine combination, but non-significantly (P > 0.05) by yohimbine. No relapse in sedation occurred. Overall, the combination of yohimbine and 4-aminopyridine produced better responses than the individual drugs, and may therefore be used for rapid reversal of xylazine-induced sedation in goats. Yohimbine or 4-aminopyridine may also be useful for this purpose but recovery may be prolonged.     

Antagonistic effects of yohimbine in pigs anaesthetised with tiletamine/zolazepam and xylazine

Twelve healthy two-month-old Landrace x Yorkshire pigs of both sexes were randomly assigned to receive either tiletamine and xylazine (zx) or zolazepam and xylazine followed 20 minutes later by yohimbine (zxy). The pigs' scores for immobilisation and analgesia, and their rectal temperature, heart rate, respiration rate, pO(2), pCO(2), alkaline phosphatase, aspartate aminotransferase, glucose and total plasma proteins were determined before and five, 25, 45, 65 and 85 minutes after the administration of the tiletamine/zolazepam and xylazine. The mean total scores for immobilisation and analgesia of the zxy pigs were significantly lower than those of the zx pigs after 85 minutes. The mean rectal temperatures of the zxy pigs were significantly lower than those of zx pigs after 25, 45 and 65 minutes. The mean respiratory rates of the zx pigs were significantly lower than those of zxy pigs after five minutes. The mean pCO(2) of the zxy pigs were significantly lower than those of zx pigs five minutes after the administration of yohimbine. The mean glucose concentration of the zxy pigs were significantly lower than those of zx pigs after 65 and 85 minutes. The mean concentration total protein of the zxy pigs were significantly lower than those of zx pigs throughout the period of anaesthesia. Both groups became laterally recumbent within three minutes. When recovering from anaesthesia, the pigs treated with yohimbine took significantly less time to achieve sternal recumbency (mean [sd] 52.2 [8.9] v 76.2 [20.6] minutes) and less time to be able to stand (mean [sd] 77.0 [9.8] v 98.7 [15.8] minutes), and walk (mean [sd] 81.3 [11.3] v 110.8 [18.6] minutes).     

Reversal of xylazine sedation in dogs.

Intramuscular injections of atipamezole (200 micrograms/kg), doxapram (2.5 mg/kg) and saline (0.1 ml/kg) were compared for their ability to reverse xylazine sedation in dogs. Atipamezole effectively reversed the sedative effects and partially reversed the cardiopulmonary effects of xylazine. Doxapram did not arouse the dogs as much as atipamezole, but it shortened the time taken for them to stand although the dogs were still ataxic.     

Cardiopulmonary effects of xylazine in dogs.

Effects of the drug xylazine were determined on arterial pH, arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2), aortic blood pressure, aortic flow, heart rate, pulse pressure, stroke volume, and peripheral resistance of dogs. The drug was given intravenously (IV) with and without atropine and was given intramuscularly (IM) without atropine. After IV administration of xylazine (1.1 mg/kg), arterial pH, PaO2, and PaCO2 values were not changed from control values. However, the drug did produce a statistically significant decrease in heart rate, decrease in aortic flow, initial increase in blood pressure followed by decrease, and increase in peripheral resistance. Stroke volume and pulse pressure were not significantly changed. Atropine (0.02 mg/kg, IV) did not significantly change any of the effects produced by xylazine. Intramuscular administration of xylazine (2.2 mg/kg) did not produce significant changes in arterial pH, PaO2, or PaCO2. Heart rate and aortic flow decreased significantly, but statistically significant changes did not occur in aortic blood pressure or peripheral resistance; however, the changes in these last 2 values were in the same direction and were of similar magnitude as those which occurred afger IV administration of xylazine.     

Effects of xylazine administration on serum amylase, pancreas-specific isoamylase and pancreatic polypeptide in normal dogs.

Changes in serum total amylase, pancreas-specific isoamylase and pancreatic polypeptide activities were measured in six dogs following multiple intramuscular injections of xylazine at 0.5 mg/kg of body weight. The activities of those analytes did not change over 24 hours of study.     

Effect of marbofloxacin on cardiovascular variables in healthy isoflurane-anesthetized dogs

OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.     

Hemodynamic effects of incremental doses of acepromazine in isoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs.Study designProspective, experimental study.AnimalsHealthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation).MethodsDogs were anesthetized with propofol (7 mg kg^–1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe′Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 μg kg^–1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe′Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 μg kg^–1 (time points ACP₁₀, ACP₂₅, ACP₅₀ and ACP₁₀₀, respectively).ResultsCompared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP₅₀ and ACP₁₀₀. Arterial oxygen content (CaO₂) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP₅₀ and ACP₁₀₀ than at ACP₁₀. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP₁₀, ACP₂₅ and ACP₁₀₀, and in two dogs at ACP₅₀.Conclusions and clinical relevanceCompared with isoflurane alone, anesthesia with acepromazine–isoflurane resulted in increased CI and decreased SVRI and CaO₂ values. These effects were dose-related, being more pronounced at ACP₅₀ and ACP₁₀₀. Under the conditions of this study, acepromazine administration did not change blood pressure.