Xylazine-ketamine-induced anesthesia in rats and its antagonism by yohimbine

A combination of xylazine and ketamine was used to anesthetize 60 male rats, and then yohimbine was given to evaluate its reversing effect on xylazine-ketamine-induced anesthesia. In experiment A, xylazine (21 mg/kg of body weight) and ketamine (45 mg/kg) were admixed and administered IM to 12 Sprague-Dawley rats. Anesthesia lasted approximately 70 minutes. The xylazine-ketamine combination also induced polyuria, bradycardia, and bradypnea. When yohimbine (2.1 mg/kg) was given intraperitoneally 20 minutes after the xylazine-ketamine injection, the rats regained consciousness and righting reflexes within approximately 10 minutes. Yohimbine also reversed the bradycardia and bradypnea and appeared to reduce the polyuria induced by the xylazine-ketamine combination. In experiment B, xylazine (15.4 mg/kg) and ketamine (33 mg/kg) were admixed and given IM to 48 Holtzman rats. The combination induced surgical anesthesia for at least 30 minutes, during which a surgical procedure involving grafting a section of the sciatic nerve into the hypothalamus was performed. In rats in which yohimbine (1 mg/kg) was given intraperitoneally 45 to 60 minutes after xylazine-ketamine administration (before natural recovery from the anesthesia), the righting reflex was apparent in less than 10 minutes.     

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.     

Comparison of five preanesthetic medicaments in pentobarbital-anesthetized dogs: antagonism by 4-aminopyridine, yohimbine, and naloxone

Effects of saline solution (groups 1, 2, and 3), xylazine (2.2 mg/kg of body weight, groups 4 and 5), acepromazine (0.1 mg/kg, groups 6 and 7), diazepam (1.0 mg/kg, groups 8 and 9), morphine (1.0 mg/kg, groups 10 and 11), or fentanyl-droperidol (0.055 ml/kg, groups 12 and 13), IM were compared in groups of atropinized dogs. Treated dogs were anesthetized to stage III, plane 2 with pentobarbital, IV. After stabilization of anesthesia, the dogs were given IV 0.5 mg of 4-aminopyridine (4-AP)/kg + 0.25 mg of yohimbine/kg (groups 2, 5, 7, and 9), or 4-AP + yohimbine + 0.04 mg of naloxone/kg (groups 3, 11, and 13). Groups 1, 4, 6, 8, 10, and 12 were given saline solution instead of test antagonists. Required dosage of pentobarbital, arousal and walk times (measured from injection of antagonists), respiratory rate, and heart rate were measured. Emergence phenomena were recorded and graded as smooth, fairly smooth, smooth in some dogs to rough in other dogs, rough, or very rough. In group 1 dogs, mean arousal time (MAT) was 279.5 minutes, mean walk time (MWT) was 583.3 minutes, and emergence was rough. In groups 4, 6, 8, 10, and 12, MAT was decreased by the sedatives to the range of 52 to 115.3 minutes and MWT was decreased to the range of 82.3 to 188.5 minutes. Emergence was smooth (groups 4 and 6), fairly smooth (groups 10 and 12), or smooth to rough (group 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of xylazine-pentobarbital anesthesia by yohimbine in ponies

Effects of yohimbine on xylazine-pentobarbital anesthesia were evaluated in ponies. Five minutes after the IV injection of xylazine (1.1 mg/kg of body weight), pentobarbital sodium (12.7 mg/kg, IV) and additional xylazine (2.2 mg/kg, IM) were given and produced anesthesia in 12 ponies for 64.0 +/- 16.4 minutes (mean +/- SD) as well as immobilization for 89.8 +/- 34.2 minutes. Eleven ponies were given yohimbine (0.1 mg/kg, IV) 50 minutes after pentobarbital dosing. In these 11 ponies, durations of anesthesia and immobilization were shorter, 52.0 +/- 1.4 and 65.5 +/- 14.8 minutes, respectively. The xylazine-pentobarbital combination caused bradycardia that was reversed by yohimbine injection. Xylazine-pentobarbital produced a small, but steady, decrease of mean arterial blood pressure, which was compounded by yohimbine administration and was evident for approximately 2 minutes. Within a minute after yohimbine injection, the ponies' respiratory rate decreased and the length of inspiration and expiration and thoracic breathing increased. This lasted approximately 2 to 3 minutes and was followed by an increase in respiratory rate. The anesthesia also produced a decrease in PaO2 that gradually returned to base line in 12 control ponies, but was more pronounced in 11 ponies given yohimbine. The PaCO2, although remaining moderately high in control ponies, returned to base line after yohimbine injection. An increased pHa was seen 60 minutes after induction of anesthesia and was especially noticeable after yohimbine administration. Decreases in the number of WBC, hemoglobin content, PCV, plasma protein and serum aspartate transaminase resulting from xylazine-pentobarbital were reversed by yohimbine. Conversely, serum glucose values and creatine kinase activities were increased by xylazine-pentobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

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)     

Effect of yohimbine on xylazine-ketamine anesthesia in cats

Xylazine and ketamine are an anesthetic combination used in feline practice for routine surgical procedures. In a controlled study, we evaluated the effects of yohimbine, an antagonist of xylazine, on the anesthesia induced by this anesthetic combination in cats. Two intramuscular doses of xylazine and ketamine (2.2 mg of xylazine/kg plus 6.6 mg of ketamine/kg and 4.4 mg of xylazine/kg plus 6.6 mg of ketamine/kg) caused approximately 60 and 100 minutes of anesthesia, respectively, in control cats. When yohimbine (0.1 mg/kg) was given intravenously 45 minutes after ketamine administration, the cats regained consciousness within 3 minutes. They were ambulatory 1 to 2 minutes after regaining consciousness. Yohimbine also reversed the bradycardia and respiratory depression elicited by xylazine-ketamine. The results indicated that yohimbine may be useful for controlling the duration of xylazine-ketamine anesthesia in cats.     

Comparative pharmacokinetics of yohimbine in steers, horses and dogs.

In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total body clearance of yohimbine was 69.6 +/- 35.1 mL/min/kg for steers, 34.0 +/- 19.4 to 39.6 +/- 16.6 mL/min/kg for horses, and 29.6 +/- 14.7 mL/min/kg for dogs. Between-species comparisons indicated that the mean area under the serum concentration versus time curve was significantly greater (P less than 0.05) in dogs than in horses. There were no significant differences (P greater than 0.05) between the means for the apparent volume of distribution, clearance, mean residence time, terminal rate constant, and area under the curve between horses given the two doses of yohimbine. The harmonic mean effective half-life (+/- pseudo standard deviation) of yohimbine was 46.7 +/- 24.4 min in steers, 52.8 +/- 27.8 to 76.1 +/- 23.1 min in horses, and 104.1 +/- 32.1 min in dogs. The data may explain why steers, horses, and dogs given certain sedatives and anesthetics do not relapse when aroused by an intravenous injection of yohimbine hydrochloride.     

Antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs

This study aimed to investigate and compare the antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs. Five dogs were used repeatedly in each of 8 groups. One group was not medicated. Dogs in the other groups received 20 μg/kg of medetomidine intramuscularly and, 0.5 h later, saline (as the control injection), 50, 100, or 300 μg/kg of atipamezole, or 50, 100, or 300 μg/kg of yohimbine intramuscularly. Urine and blood samples were taken 11 times over 24 h for measurement of the following: urine volume, specific gravity, and creatinine concentration; urine and plasma osmolality; urine and plasma concentrations of electrolytes and arginine vasopressin (AVP); and the plasma concentration of atrial natriuretic peptide (ANP). Both atipamezole and yohimbine antagonized the diuretic effect of medetomidine, inhibiting medetomidine-induced decreases in urine specific gravity, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and AVP and reversing both the medetomidine-induced increase in plasma concentrations of sodium, potassium, and chloride and the medetomidine-induced decrease in the plasma AVP concentration. Atipamezole significantly stimulated ANP release. The antidiuretic action of yohimbine was more potent than that of atipamezole but was not dose-dependent, in contrast to the action of atipamezole. The effects of these drugs may not be due only to actions mediated by α₂-adrenoceptors.     

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.     

Arrhythmogenicity of dopamine and its effects on hemodynamics in dogs under halothane anesthesia

The arrhythmogenicity of dopamine, its effects on cardiac function, hemodynamics, and diuresis under halothane anesthesia were evaluated in dogs. The induction time of arrhythemias and the effect of arrhythmias on cardiac function, hemodynamics, and diuresis were determined after infusion of dopamine for 30-min period at increasing doses of 3, 5, 7, 10, and 15 micrograms/kg/min. The results were as follows. 1. Arrhythmia induction percentage was 28.6% at 5 micrograms/kg/mn, 42.9% at 7 micrograms/kg/min, 25% at 10 micrograms/kg/min, and 41.7% at 15 micrograms/kg/min. The induction time of arrhythemias (sec) was 459 at 5 micrograms/kg/min, 332 at 7 micrograms/kg/min, 152 at 10 micrograms/kg/min, and 279 at 15 micrograms/kg/min. No arrhythmias were present at 3 micrograms/kg/min. 2. Heart rate and myocardial oxygen consumption was increased in the arrhythmia-induced group compared to the non-arrhythmia-induced group. 3. Myocardial contractility, mean aortic pressure, mean pulmonary arterial pressure, and diuresis increased dose-dependently in the non-arrhythmia-induced group; however, these measures were increased in the arrhythmia-induced group without regard to dose.     

犬的硬膜外麻醉

麻醉效果的好坏直接影响到相应的手术及其操作的成败。本文通过对硬膜外麻醉机理、犬脊椎解剖结构、硬膜外麻醉药物的介绍,对临床上硬膜外麻醉的适用情况、药物选择进行介绍。