Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies

Eight ponies were anesthetized with a solution containing 50 mg of guaifenesin, 1 mg of ketamine, and 0.5 mg of xylazine X ml-1 of 5% dextrose in water. Anesthesia was induced by IV injection (1.1 ml X kg-1), followed by continuous IV infusion at 2.75 ml X kg-1 X hr-1. Heart rate, rate-pressure product, mean pulmonary artery pressure, and standard bicarbonate were not significantly changed throughout the study. Systolic, diastolic, and mean arterial pressures and left ventricular stroke work index were significantly decreased at 5 and 15 minutes after a bolus of the anesthetic solution was injected. Systolic blood pressure returned to within the base-line range at 30 minutes, but diastolic and mean arterial pressures were significantly decreased throughout the study. Cardiac index and arterial pH were decreased at 5 minutes only. Systemic vascular resistance was significantly decreased 60 minutes after bolus injection was given. Hypoventilation, as indicated by increased PaCO2, occurred 5 minutes after bolus injection was given.     

Cardiopulmonary effects of romifidine/ketamine or xylazine/ketamine when used for short duration anesthesia in the horse

The cardiovascular changes associated with anesthesia induced and maintained with romifidine/ketamine versus xylazine/ ketamine were compared using 6 horses in a cross over design. Anesthesia was induced and maintained with romifidine (100 microg/kg, IV)/ketamine (2.0 mg/kg, IV) and ketamine (0.1 mg/kg/min, IV), respectively, in horses assigned to the romifidine/ ketamine group. Horses assigned to the xylazine/ketamine group had anesthesia induced and maintained with xylazine (1.0 mg/kg, IV)/ketamine (2.0 mg/kg, IV) and a combination of xylazine (0.05 mg/kg/min, IV) and ketamine (0.1 mg/kg/min, IV), respectively. Cardiopulmonary variables were measured at intervals up to 40 min after induction. All horses showed effective sedation following intravenous romifidine or xylazine and achieved recumbency after ketamine administration. There were no significant differences between groups in heart rate, arterial oxygen partial pressures, arterial carbon dioxide partial pressures, cardiac index, stroke index, oxygen delivery, oxygen utilization, systemic vascular resistance, left ventricular work, or any of the measured systemic arterial blood pressures. Cardiac index and left ventricular work fell significantly from baseline while systemic vascular resistance increased from baseline in both groups. The oxygen utilization ratio was higher in the xylazine group at 5 and 15 min after induction. In conclusion, the combination of romifidine/ketamine results in similar cardiopulmonary alterations as a xylazine/ketamine regime, and is a suitable alternative for clinical anesthesia of the horse from a cardiopulmonary viewpoint.     

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg^?1, romifidine 0.08 mg kg^?1, or xylazine, 1 mg kg^?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.     

Hemodynamic Effects of Atropine and Glycopyrrolate in Isoflurane-Xylazine-Anesthetlzed Dogs

Alterations in parasympathetic tone are partially responsible for xylazine's hemodynamic effects. The purpose of this study was to evaluate and compare the hemodynamic changes caused by the administration of intravenous (IV) atropine or glycopyrrolate after IV xylazine in isoflurane-anesthetized dogs. Six healthy beagles (8.2 to 10.7 kg) were used in two trials separated by 7 days. Anesthesia was induced and maintained with isoflurane in 100% oxygen with controlled ventilation. Once constant end-tidal isoflurane (1.8%) and arterial partial pressure of carbon dioxide (35 to 45 mm Hg) values were reached, baseline data were recorded and xylazine (0.5 mg/kg, IV) was given. In trial 1 atropine (0.1 mg/kg, IV) was given 5 minutes after xylazine, and in trial 2 glycopyrrolate (0.025, mg/kg, IV), was given 5 minutes after xylazine. Hemodynamic variables were recorded 3 minutes after xylazine and 3 minutes after anticholinergic administration. In trial 2, bilateral vagotomies were performed 10 minutes after glycopyrrolate, and hemodynamic variables were recorded 3 minutes later. Heart rate, cardiac index, and stroke index decreased; arterial pressure and systemic vascular resistance increased after xylazine. Heart rate, cardiac index, and rate pressure product increased after anticholinergic administration. Significant differences between atropine and glycopyrrolate were not observed in any of the hemodynamic parameters. Similarly, significant differences between glycopyrrolate and bilateral vagotomy were not observed. The authors conclude that intravenous atropine and glycopyrrolate have equivalent hemodynamic actions during the increased pressure phase after IV xylazine in isoflurane-anesthetized dogs; that intravenous atropine and glycopyrrolate produce comparable increases in heart rate and that both may increase the risk of myocardial hypoxia associated with an increase in rate pressure product; and that vagal blockade produced by high-dose glycopyrrolate (.025 mg/kg, IV) is similar to that produced by bilateral vagotomy.     

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)     

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.     

Preliminary Results of Behavioral and Cardiopulmonary Effects of a Constant Rate Infusion of Remifentanil–Xylazine for Sedation in Horses

Standing surgical procedures are performed commonly in horses under sedation. The use of a xylazine and remifentanil combination has not been investigated in horses. We proposed to evaluate behavioral and cardiopulmonary effects of an intravenous (IV) infusion of xylazine with remifentanil for sedation in horses. Xylazine (0.8 mg/kg IV) followed in 3 minutes by remifentanil (0.0005 mg/kg IV), and a constant rate infusion of xylazine and remifentanil (0.65 mg/kg/h; 0.0225 mg/kg/h, respectively) was administered in three horses. Heart rate, respiratory rate (RR), arterial blood pressures, quality of sedation, pH, partial pressure of arterial CO₂ (PaCO₂), partial pressure of arterial O₂ (PaO₂), ataxia, sedation, and sedation overall outcome were assessed. Heart rate and RR remained within normal values during sedation without significant changes from baseline. Systolic, mean, and diastolic arterial blood pressures were increased during sedation. There were no significant changes in pH, PaCO₂, and PaO₂. Sedation developed immediately after injection of xylazine in the three horses but did not increase after remifentanil bolus or IV infusion of both drugs. None of the mares had ataxia. Adverse effects during and after sedation were present: excitement, increase in locomotor activity, and decrease in the gastrointestinal motility. The combination of xylazine and remifentanil sedation protocol produces adverse effects. This protocol cannot be recommended for clinical conditions, at the described doses.     

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)     

Effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange in endotoxemic pigs

The effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange were determined in anesthetized 10- to 14-week-old pigs after they were endotoxemic for 1 or 4.5 hours. Saline solution was given to controls (group 1). Escherichia coli endotoxin (055-B5) was infused IV at a dosage of 5 micrograms/kg for 1 hour (group 2). In group 3, endotoxin was infused at 5 micrograms/kg the first hour plus a continuous infusion of endotoxin at 2 micrograms/kg/hr. Ketanserin, a specific serotonin receptor antagonist, was infused IV (300 micrograms/kg) after pigs were endotoxemic for 1 or 4.5 hours (groups 2 and 3, respectively). At 1 hour of endotoxemia, mean pulmonary artery pressure and pulmonary vascular resistance were increased, and cardiac index was decreased. Ketanserin caused a small attenuation of the increases in mean pulmonary artery pressure and pulmonary vascular resistance, indicating that serotonin may have a small role in the endotoxin response at 1 hour. At 4.5 hours of endotoxemia, mean pulmonary artery pressure, pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen gradient were increased, and cardiac index and lung dynamic compliance were decreased; ketanserin significantly attenuated the endotoxin-induced changes in cardiac index, mean pulmonary artery pressure, pulmonary vascular resistance, and lung dynamic compliance. Ketanserin also decreased the blood temperature after pigs were endotoxemic for 4.5 hours. However, the endotoxin-induced increases (at 4.5 hours) in alveolar-arterial oxygen gradient and alveolar dead space ventilation were not acutely reversed by ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.     

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.     

Antagonistic effect of atipamezole on xylazine-induced sedation, bradycardia, and ruminal atony in calves.

Three doses of an alpha 2-adrenoreceptor antagonist, atipamezole, were administered to reverse xylazine-induced sedation, bradycardia, and ruminal atony in calves. Once a week for 4 weeks, each of 6 calves was administered IV 1 treatment of: 0.3 mg of xylazine/kg of body weight, followed in 10 minutes by 1 ml of 0.9% NaCl; 0.3 mg of xylazine/kg, followed in 10 minutes by 3 micrograms of atipamezole/kg; 0.3 mg of xylazine/kg, followed in 10 minutes by 10 micrograms of atipamezole/kg; or 0.3 mg of xylazine/kg, followed in 10 minutes by 30 micrograms of atipamezole/kg. The order of the 4 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 33.6 +/- 7.1 minutes (mean +/- SEM). Atipamezole administered at dosages of 3, 10, and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 20.5 +/- 3.0, 10.2 +/- 0.2, and 9.3 +/- 0.5 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Atipamezole given at 3, 10, and 30 micrograms/kg shortened the time from onset of lateral recumbency to standing to 40.2 +/- 6.9, 12.8 +/- 1.1, and 10.0 +/- 0.7 minutes, respectively. Drowsiness was found in calves given the lowest dosage of atipamezole (3 micrograms/kg) after the calves stood. Atipamezole given at dosages of 10 and 30 micrograms/kg reversed xylazine-induced ruminal atony in a dose-dependent manner. In addition, 30 micrograms of atipamezole/kg reversed xylazine-induced bradycardia, but the lower dosages of this antagonist did not. Results indicated that 30 micrograms of atipamezole/kg should be a useful antidote for xylazine overdose in cattle.     

The anti-nociceptive and cardiopulmonary effects of extradural fentanyl–xylazine in sheep

Objective To compare the anti‐nociceptive effects of extradural xylazine, fentanyl and a xylazine–fentanyl combination in sheep, and to measure the cardiopulmonary effects of the xylazine–fentanyl combination. Study design Prospective, randomized study. Animals Twenty‐five half‐merino ewes 2–4 years of age and body mass 54.2 ± 1.1 kg. Methods Six sheep in group 1 received 0.2 mg kg^?1 xylazine by extradural injection, six in group 2 received fentanyl 1.5 µg kg^?1 and 13 in group 3 received the combination of both treatments. In all groups, drugs were mixed with saline (0.15 mL kg^?1 before injection). Pulmonary and carotid arterial catheters were placed in seven sheep of group 3 which were used to evaluate cardiopulmonary effects. Anti‐nociception was determined by the response to electrical stimulation (40 V for 1.5 milliseconds) of the left flank and by superficial and deep muscular ‘pinpricking’ stimulation of the pelvic and thoracic limbs and thoracolumbar region. Results Lack of response to electrical stimulation at the left flank was present in 10 ± 1.1 minutes (mean ± SEM) (group 1) and in 4.5 ± 0.5 minutes in group 3. The duration of lack of response to electrical stimulation at the left flank was 96 ± 6 minutes in group 1 and 315 ± 6 minutes in group 3. Responses persisted in group 3. Significant decreases (p < 0.05) in cardiac output 30, 45, 60 and 90 minutes after injection, and in cardiac work at 30 and 45 minutes were observed in the seven animals of group 3. Arterial blood pH was lowest at 90 minutes, arterial bicarbonate was lowest at 60 minutes and values for both arterial and mixed venous base excess increased significantly at 60 and 90 minutes. There was no significant change from baseline values in heart rate, mean arterial blood pressure, respiratory rate, body temperature, systemic vascular resistance, arterial and mixed venous PO₂, PCO₂, oxygen saturation, blood oxygen content, haemoglobin concentration, mixed venous blood bicarbonate and pH. Conclusions Fentanyl decreases the onset time and prolongs the duration of anti‐nociception produced by xylazine. The combination decreases cardiac output but is without significant respiratory effects. Clinical relevance Further studies are required to show that surgery is possible in sheep after extradural xylazine–fentanyl injection.     

Effects of xylazine on cecal mechanical activity and cecal blood flow in healthy horses

Mechanical activity of the cecal body, lateral cecal arterial blood flow, carotid arterial pressure, and heart rate were measured in 6 conscious healthy horses 30 minutes before and for 120 minutes after IV administration of xylazine at dosages of 1.1 mg/kg of body weight, 0.55 mg/kg, and 0.275 mg/kg. Xylazine at a dosage of 1.1 mg/kg reduced the mean motility index (the product of the mean amplitude of contractions and the total duration of contractile activity divided by the recording time) of the circular and longitudinal muscle layers for the first, second, third, and fourth 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.55 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first and second 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.275 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first 30-minute period after administration of xylazine. Mean lateral cecal arterial blood flow was significantly (P less than 0.05) lower than the base-line value at 2 and 4 minutes after administration of all 3 xylazine dosages and at 8 minutes after administration of xylazine dosages of 1.1 mg/kg and 0.55 mg/kg. All dosages of xylazine caused transient hypertension and bradycardia, followed by hypotension.     

Antagonistic effect of idazoxan on xylazine-induced central nervous system depression and bradycardia in calves

Two doses of an alpha 2-adrenoreceptor antagonist, idazoxan, were administered to reverse the CNS depressant and bradycardia effects of xylazine in calves. Once a week for 3 weeks, each of 6 calves were administered IV one treatment of: (1) 0.2 mg of xylazine/kg of body weight followed in 10 minutes by 1 ml of 0.9% NaCl, (2) 0.2 mg of xylazine/kg followed in 10 minutes by 10 micrograms of idazoxan/kg, or (3) 0.2 mg of xylazine/kg followed in 10 minutes by 30 micrograms of idazoxan/kg. The order of the 3 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 27.2 +/- 3.0 minutes (mean +/- SEM). Idazoxan administered at dosages of 10 and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 11.5 +/- 0.8 and 10.3 +/- 0.2 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Idazoxan given at dosages of 10 and 30 micrograms/kg shortened the time to standing to 16.8 +/- 1.7 and 11.3 +/- 0.2 minutes, respectively. Idazoxan given at a dosage of 30 micrograms/kg also reversed xylazine-induced bradycardia. Results indicated that idazoxan should be a useful antidote for xylazine overdose in cattle.     

Effects of ketamine, xylazine, and a combination of ketamine and xylazine in Pekin ducks

Effects of ketamine, xylazine, and a combination of ketamine and xylazine were studied in 12 male Pekin ducks (7 to 12 weeks old; mean [+/- SD] body weight, 3.1 +/- 0.3 kg). After venous and arterial catheterization and fixation of a temperature probe in the cloaca, each awake duck was confined, but not restrained, in an open box in a dimly lit room. Blood pressure and lead-II ECG were recorded. Three arterial blood samples were collected every 15 minutes over a 45-minute period (control period) and were analyzed for pHa, PaCO2 and PaO2. After the control period, each duck was assigned at random to 1 of 3 drug groups: (1) ketamine (KET; 20 mg/kg of body weight, IV), (2) xylazine (XYL; 1 mg/kg, IV), and (3) KET + XYL (KET 20 mg/kg and XYL, 1 mg/kg; IV). Measurements were made at 1, 5, 10, 15, 30, 45, 60, and 90 minutes after drug administration. All ducks survived the drug study. Cloacal temperature was significantly (P less than or equal to 0.05) increased above control cloacal temperature at 90 minutes after the administration of ketamine, and from 10 through 90 minutes after administration of ketamine plus xylazine. In ducks of the KET group, pHa, PaCO2, and PaO2, remained unchanged after administration of the drug. In ducks of the XYL group, pHa and PaO2 decreased significantly (P less than or equal to 0.05) from control values for all time points up to and including 15 minutes after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of xylazine and detomidine in horses

The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.     

Effects of ischemia and dimethyl sulfoxide on equine jejunal vascular resistance, oxygen consumption, intraluminal pressure, and potassium loss

Physiologic effects of 1 hour of ischemia and 1 hour of reperfusion on equine jejunum and protective effects of systemic administration of dimethyl sulfoxide (DMSO, 1 g/kg of body weight) were investigated in 18 ponies, using neurally intact segments of jejunum perfused at constant flow with heparinized blood. Ponies were allotted to 4 groups: group 1, saline solution administered (control, n = 3); group 2, DMSO administered (DMSO, n = 3); group 3, ischemia induced and saline solution administered (ischemia, n = 6); and group 4, ischemia induced and DMSO administered (ischemia-DMSO, n = 6). Intestinal vascular resistance (R, mm of Hg/ml/min/100 g), oxygen consumption (VO2, ml/min/100 g), frequency and amplitude of rhythmic changes in intraluminal pressure, intestinal compliance (C, ml/mm of Hg), and arteriovenous potassium concentration difference (delta AV [K+], mEq/L) were determined and compared with stable preischemic values within groups. There were no significant changes in any variable in ponies of groups 1 or 2. In ponies of group 3, significant (P less than or equal to 0.05) changes included: an initial increase in R during reperfusion, followed by a decrease to values below preischemic values by 15 minutes of reperfusion; decreased VO2 during the entire reperfusion period; increased amplitude of rhythmic contractions during initial reperfusion; decreased frequency of rhythmic contractions during ischemia; and increased delta AV [K+] during initial reperfusion. Changes in ponies of group 4 were identical to changes in ponies of group 3, with the exception that DMSO administration prevented the decrease in R during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of pre-anesthetic administration of xylazine on the cardiovascular responses to dobutamine in halothane anaesthetized horses

Studies evaluating the effects of dobutamine in horses do not consistently report increases in cardiac output despite increases in arterial blood pressure. The concurrent administration of the α₂ agonist clonidine, in people, inhibited the chronotropic effects of dobutamine and increased left ventricular stroke work ( Zimpfer et al. 1982 ). Our study was performed to determine if pre‐medication with an α₂ agonist affects the response to dobutamine in anaesthetized horses. Eleven horses were anaesthetized on four separate occasions for one of four randomly assigned treatments; (I) no xylazine, no dobutamine (II) xylazine, no dobutamine (III) no xylazine, dobutamine, and (IV) xylazine, dobutamine. Horses received 0.02 mg kg^?1 of butorphanol IV 10 minutes prior to anesthetic induction. Two minutes prior to induction, groups II and IV received 0.5 mg kg^?1 of IV xylazine. Anaesthesia was induced with 6–7 mg kg^?1 of thiopental and maintained with halothane. End‐tidal halothane concentrations were maintained between 1.1 and 1.2% in groups I and III, and 0.9–1.0% for groups II and IV. Heart rate, cardiac output, right atrial pressure, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure were recorded 30 minutes after beginning halothane anaesthesia (T10). Cardiac output was estimated using Lithium dilution ( Linton et al. 2000 ). Baseline measurements were repeated twice, at 5‐minute intervals (T5 and T0). At time 0 (T0), an IV infusion of either saline (100 mL hour^?1) or dobutamine (0.001 mg kg^?1 minute^?1) was started and data recorded at 5‐minute intervals for 30 minutes (T5 – T30). Stroke volume and systemic vascular resistance (SVR) were calculated. Data were analysed using repeated measures anova (p < 0.01 significant) and Newman–Keuls for multiple comparisons. Cardiac output and stroke volume increased over time in groups III and IV. Cardiac index was higher in groups III and IV than in groups I and II from T10 until completion of the study. Estimates of cardiac index at T30 for groups I–IV were 45 ± 9, 46 ± 11, 71 ± 11, and 78 ± 19 mL kg^?1 minute^?1, respectively (mean ± SD). Stroke index was higher in groups III and IV than in groups I and II from T15 to T30. Values for stroke index at T30 for groups I–IV were 0.98 ± 0.19, 1.11 ± 0.18, 1.46 ± 0.21, 1.74 ± 0.33 mL kg^?1. Heart rate decreased from T10–T30 in groups I and II. Heart rate was greater in groups I and III than in groups II and IV at T5 and T0. Values for heart rate at T0 for groups I–IV were 48 ± 5, 42 ± 5, 50 ± 4, 43 ± 4 beats minute^?1. Systolic arterial pressure, DAP and MAP were higher in groups III and IV than in groups I and II from T5 to T30. There were no differences in SVR between groups. Dobutamine at 0.001 mg kg^?1 minute^?1 increased cardiac output, blood pressure, and stroke volume. Premedication with xylazine at 0.5 mg kg^?1 did not appear to affect the response to dobutamine.     

Histopathologic alterations induced in the lungs of sheep by use of alpha2-adrenergic receptor agonists

OBJECTIVE: To study effects of central- and peripheral-acting alpha2-adrenergic receptor agonists on lung parenchyma, platelets, and pulmonary intravascular macrophages (PIM) of sheep. ANIMALS: 12 healthy mature female sheep. PROCEDURE: Group-1 (control, n = 2) sheep received 5 ml of physiologic saline solution IV and were euthanatized 3 minutes later. Sheep of group 2 (n = 8) received xylazine (150 microg/kg of body weight, IV), then 2 sheep each were euthanatized 3, 10, or 60 minutes, or 12 hours later. Sheep (n = 2) of group 3 were given ST-91 (30 microg/kg, IV), then were euthanatized 3 minutes later. Immediately after euthanasia, the lungs were fixed intratracheally and tissue was obtained for light and electron microscopy after 1 hour. RESULTS: Pulmonary parenchymal damage or morphologic alterations in PIM and platelets were not evident in control sheep. Three minutes after xylazine administration, morphologic changes in PIM were appreciable. After 10 minutes, extensive damage to the capillary endothelium and alveolar type-I cells, intra-alveolar hemorrhage, and interstitial and alveolar edema were evident. Most PIM had complete internalization of the surface coat. Similar changes were seen 60 minutes after xylazine administration; however, by 12 hours, morphologic features of PIM and lung parenchyma were almost completely restored. Evidence of PIM activation, obvious damage to capillary endothelium, and extensive pulmonary edema also were evident 3 minutes after ST-91 administration. CONCLUSIONS: XYLAZINE induces severe pulmonary parenchymal damage when administered at clinical sedative doses in sheep; morphologic changes in PIM within 3 minutes after administration of these drugs are substantial; and platelet aggregation is not apparent.