Effects of acepromazine, xylazine and propofol on spinal reflexes in healthy dogs.

BACKGROUND: In the neurological examination, it is crucial to identify the possible location of the lesion in order to determine the appropriate treatment process. In aggressive animals, chemical restraint may be necessary due to their non-cooperative behaviour. However, sedatives may distort the results of examinations. Therefore, a drug should be found that has minimal impact on the examination results. OBJECTIVES: To investigate the effects of acepromazine, xylazine, and propofol on spinal reflexes in healthy dogs. METHODS: In a randomized, blinded study, ten native adult mixed-breed dogs were participated in three groups with a 1-week washout period between each group. Before performing each step, the spinal reflexes were evaluated. Then, in the first group, acepromazine (0.05 mg/kg, IM), in the second group, xylazine (1 mg/kg, IM), and in the third group, propofol (3 mg/kg, IV for initial bolus and 0.1 mg/kg/min for maintenance) were injected for sedation. The spinal reflexes were reevaluated at maximum sedation and at 15, 30, and 45 min thereafter. RESULTS: Acepromazine increased the patellar reflex and decreased the panniculus reflex. Xylazine increased the cranial tibial reflex and decreased the panniculus reflex, while propofol decreased the withdrawal, and extensor carpi radialis reflexes, and suppressed the palpebral and gag reflexes. CONCLUSIONS: The drugs used in the present study did not have a significant impact on the most important reflexes evaluated in neurological examinations. Among the drugs, acepromazine has the least effects compared to other drugs, making it a suitable choice for sedation.

Perioperative Change of High-Sensitive Cardiac Troponin I Concentration in Cats According to Three Different Anaesthesia Protocols.

BACKGROUND: Cardiac troponin I, a particular biomarker, is released into the bloodstream in response to myocardial injury. OBJECTIVES: To evaluate perioperative changes in high-sensitivity cardiac troponin I (hs-cTnI) concentration during ovariohysterectomy in cats undergoing three different anaesthesia protocols. METHODS:  Twenty-one female mixed-breed cats owned by clients aged (2.2 ± 0.7 years) and weight (3.2 ± 0.5 kg) were included in our study. The cats were divided into three groups: propofol-isoflurane (PI) group (n = 7), xylazine-ketamine (XK) group (n = 7) and xylazine-isoflurane (XI) group (n = 7). After pre-anaesthetic propofol (6 mg/kg IV) was administered to cats in Group PI, a mask was placed, and anaesthesia was maintained with 3.0% isoflurane in oxygen. Cats in Group XK underwent general anesthetization with xylazine hydrochloride (2 mg/kg IM) and, 10 min later, ketamine hydrochloride (10 mg/kg IM). Cats in Group XI were administered xylazine hydrochloride (2 mg/kg IM), and then anaesthesia (3.0% isoflurane and oxygen) was continued with a mask. Blood samples were collected from all cats; preoperatively and postoperatively at 0 and 12 h (Pre-, Post-0 h and Post-12 h, respectively). Serum hs-cTnI concentrations were measured with the Advia Centaur TnI-Ultra. RESULTS: In all 21 cats, hs-cTnI concentration increased at Post-0 h and 12 h measurement points compared to Pre-. In the XK group, hs-cTnI concentrations exhibited a significant increase at the Post-0 h (51.30 ng/L) and Post-12 h (157.70 ng/L) time points compared to Pre- (6.70 ng/L) (p < 0.05). CONCLUSIONS: The XK group increased the concentration of hs-cTnI more than other protocols. In the PI group, the increase in hs-cTnI concentrations at Post-0 and 12 h increased less than the other two groups (p < 0.05). The PI group was found to induce less myocardial damage.

TILETAMINE-ZOLAZEPAM-XYLAZINE ANESTHESIA IN EX SITU BLACK-HANDED SPIDER MONKEYS (ATELES GEOFFROYI SSP.).

Black-handed spider monkeys (Ateles geoffroyi ssp.) are endangered in Mexico. Safe anesthetic protocols are important for in situ and ex situ conservation problems. Such protocols are scarce in the literature; nor have safety and physiologic responses been reported. High doses and volume are a counter side for field immobilizations. We tested an anesthetic protocol with a combination of tiletamine-zolazepam (5 mg/kg) plus xylazine (1 mg/kg) in 14 black-handed spider monkeys under human care from two facilities in Mexico. Physiological parameters such as HR, RR, T, SPO2, systolic arterial pressure (), diastolic arterial pressure (DAP), and median arterial pressure (MAP) were obtained. HR and RR decreased over time, but T increased significantly during the anesthetic time for the whole group; RR and T decreased for juveniles only. Variation between individuals was observed for HR, RR, and DAP. Volume reduction of drugs was achieved compared to previously reported anesthesia protocols. Induction time was fast (6.2 ± 10.4 min) and no tail prehension was seen. Recovery was prolonged (mean and SD). Physiologic parameters remained stable throughout. The protocol proved to be safe for the chemical immobilization of black-handed spider monkeys.

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 µg/kg/min xylazine, 1 µg/kg/min butorphanol, 200 µg/kg/min propofol) and 9 mL/kg/h (G9; 15 µg/kg/min xylazine, 1.5 µg/kg/min butorphanol 300 µg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.

Adjusting and validating a procedure for parenteral anaesthesia in neonatal mice.

For neonatal pups, parenteral anaesthesia is said to be not reliable as low doses induce no anaesthesia whereas high doses render high mortality rates. In this work we have adapted parenteral anaesthesia procedures approved for pups >7 days of age, to anaesthetize neonatal animals (postnatal days 3-4; P3-P4) for keeping them immobile for a long period. In our first experiment we analysed the behaviour of P3-P4 mouse pups for 70 min after intraperitoneal administration of low (37.5/3.75 mg/kg) or high (50/5) doses of a ketamine/xylazine anaesthetic mixture, both in the low range as compared with dosages employed in adults. Pups became immobile in ≈7 min and remained immobile for ≈45 min, irrespective of the age and dose of anaesthesia, younger pups (P3) being apparently more sensitive to the dosage. In the second experiment, we studied the response of P3 pups to mildly nociceptive stimulations, performed with a 4.0 g von Frey filament applied to the dorsal aspect of their paws. These stimuli elicited reaction in 100% of the cases in non-anaesthetized pups. The results indicate that the high dose significantly reduced responses as compared with the low dose of anaesthesia. With the low dose, <40% of the pups were unresponsive to nociceptive stimulation, whereas the high dose resulted in 50-60% of the animals not responding. Mortality was low irrespective of age or dose, suggesting that doses can be further increased if needed for invasive experimental procedures.

Emotional temperaments in advanced pregnant goats and its relationship with the feto-maternal blood flow and placentome echotexture.

The current study aimed to investigate the effect of xylazine sedation (non-sedated versus sedated conditions) and animal temperament on the fetal and maternal hemodynamics during the late stage of gestation in goats. In addition, it aimed to study the concentrations of cortisol and the echotexture of the placentome. Fourteen goats were assigned into two equal groups (n = 7, each) based on the animal's emotional temperament (calm versus nervous groups). All goats were examined for assessment of the blood flow within the fetal aorta (FA), umbilical artery (UMA), and middle uterine artery (MUA) using color-pulsed Doppler ultrasonography. Goats were exposed to light sedation using the recommended dose of xylazine (0.05 mg/Kg Bw) intramuscularly. Goats in each group were reassessed for the studied parameters after sedation. Blood samples were drawn to determine the concentrations of cortisol. Placentome echotexture pixel intensity (PXI) was evaluated using computer image analysis software. Results revealed the significant impact of the xylazine sedation on the Doppler indices of the blood flow within the measured arteries (FA, UMA, and MUA), the PXI of placentome echotexture, and cortisol concentrations. The emotional temperament of goats had significant effects on the blood flow parameters of the MUA and UMA, concentrations of cortisol, and the PXI of the placentome. The interaction effect (sedation x temperament) was noticed in the measured parameters of the UMA blood flow, fetal heart rate, and cortisol concentrations. In conclusion, xylazine sedation and emotional temperaments induced alterations in the echotexture of the placentomes as well as the hemodynamic parameters of late-stage pregnant goats without affecting the pregnancy outcomes.

Sedation with dexmedetomidine-butorphanol or xylazine-butorphanol continuous intravenous infusions during unilateral ovariectomy in standing donkeys.

BACKGROUND: Intravenous infusions of alpha-2 adrenoceptor sedatives and opioids can potentially facilitate surgery in donkeys while standing. Literature on this subject matter is scant. OBJECTIVES: Evaluation of efficacy of sedation from α2-adrenoceptors (dexmedetomidine or xylazine) and butorphanol during ovariectomy in standing donkeys. STUDY DESIGN: Randomised, masked in vivo experiment. METHODS: Thirteen female donkeys were sedated with butorphanol (0.05 mg/kg bwt followed by 0.05 mg/kg bwt/h) IV. Concomitantly, 6 of the 13 jennies were sedated with dexmedetomidine 2.5 mcg/kg bwt followed by 2.5 mcg/kg bwt/h (Dex-B group), while seven jennies were sedated with xylazine 0.5 mg/kg bwt followed by 0.5 mg/kg bwt/h (Xyl-B group). A line block of the left flank and an infiltration block around uterine ligament were performed with lidocaine. While the jennies underwent ovariectomies standing, sedation scores and head height above ground were assessed at 2 and 10 min after sedative boluses and every 10 min thereafter. If sedation was too light or too deep, the dose of dexmedetomidine or xylazine was increased or decreased by 25% of the original infusion rate, while butorphanol infusion rate was constant. Physiological parameters were measured. Normally distributed data were compared using the two-sample t test while repeatedly measured data were tested for differences between and within groups using repeated measures analysis of variance (ANOVA) by ranks followed by a Wilcoxon test with Tukey Honest Significant Difference for multiple testing. Statistical significance was set at p < 0.05. RESULTS: Both Dex-B and Xyl-B caused moderate to marked sedation adequate for ovariectomy in donkeys. Evident sedation was absent by 60 min of termination of infusions. No adverse physiological effects were observed. MAIN LIMITATIONS: Study on ovariectomy cases only, no pharmacokinetic profiling. CONCLUSIONS: Dexmedetomidine or xylazine and butorphanol sedation is feasible for ovariectomy in standing donkeys.

The effects of repeated doses of xylazine-ketamine and medetomidineketamine anesthesia on DNA damage in the liver and kidney

Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys. Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated. Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression. Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.

Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain.

Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021).

Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine.

Mouse fMRI under anesthesia has become increasingly popular due to improvement in obtaining brain-wide BOLD response. Medetomidine with isoflurane has become well-accepted for resting-state fMRI, but whether this combination allows for stable, expected, and robust brain-wide evoked response in mice has yet to be validated. We thus utilized intravenous infusion of dexmedetomidine with inhaled isoflurane and intravenous infusion of ketamine/xylazine to elucidate whether stable mouse physiology and BOLD response are obtainable in response to simultaneous forepaw and whisker-pad stimulation throughout 8 h. We found both anesthetics result in hypercapnia with depressed heart rate and respiration due to self-breathing, but these values were stable throughout 8 h. Regardless of the mouse condition, brain-wide, robust, and stable BOLD response throughout the somatosensory axis was observed with differences in sensitivity and dynamics. Dexmedetomidine/isoflurane resulted in fast, boxcar-like, BOLD response with consistent hemodynamic shapes throughout the brain. Ketamine/xylazine response showed higher sensitivity, prolonged BOLD response, and evidence for cortical disinhibition as significant bilateral cortical response was observed. In addition, differing hemodynamic shapes were observed between cortical and subcortical areas. Overall, we found both anesthetics are applicable for evoked mouse fMRI studies.

Xylazine or detomidine in dairy calves: a comparison of clinically relevant pharmacodynamic parameters under sedation.

OBJECTIVE: Chemical restraint in dairy calves is necessary to enable diagnostic and surgical procedures. It is unclear whether xylazine or detomidine differ with regard to desirable and unwanted effects. MATERIAL AND METHODS: In a prospective randomized interventional study, 10 healthy Holstein-Friesian calves (age range 3-6 month) were sedated with either xylazine (0.1 mg/kg, Group X, n = 5) or detomidine (0.03 mg/kg, Group D, n = 5) intravenously, followed by butorphanol (0.1 mg/kg i. v.) in all animals. Characteristics of sedation and selected pharmacodynamic parameters were compared between groups using a non-parametric Mann-Whitney U test. RESULTS: All calves (5/5) in Group X and (3/5) calves in Group D became laterally recumbent within 5 minutes. Two calves (40 %) in Group D remained standing and could not been positioned in lateral recumbency 15 minutes after initial administration of the sedation agents. Sedation scores, onset and duration of sedation did not differ between groups. Heart and respiratory rate decreased in both groups. Mean arterial pressure was with around 30 mmHg significantly higher in Group D (t25, t30, t35, t40 with p = 0.018, 0.036, 0.029 and 0.016, respectively). In Group X, glucose level (t60) and packed cell volume (t30) were significantly lower (p = 0.032 and 0.048, respectively). CONCLUSION: and clinical relevance The xylazine-butorphanol combination provided reliable recumbent chemical restraint. With detomidine-butorphanol recumbency failed in some individuals, but a sufficient clinical sedation was achieved. Based on the limited monitoring used in this study, the side effects are of minor clinical relevance in healthy individuals.

The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model.

Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.

A Comparison of Ketamine or Etomidate Combined with Xylazine for Intraperitoneal Anesthesia in Four Mouse Strains.

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has been used in both human and veterinary medicine yet has not been widely studied in mice. The purpose of this study was to evaluate etomidate-xylazine (EX) anesthesia as an alternative to KX. We hypothesized that EX would be as safe and effective as KX, with both sex- and strain-dependent differences. Male and female Crl:CD1(ICR), C57BL/6NCrl, BALB/cJ and NU/J mice were given a single IP dose of ketamine 100 mg/kg and xylazine 10 mg/kg or etomidate 20 mg/kg and xylazine 10 mg/kg. Sedation times were similar between KX and EX, with CD1 mice exhibiting shorter sedation times. Surgical anesthesia was achieved in 44% of EX mice, compared with 4% of KX mice. C57BL/6NCrl mice were significantly more likely to achieve surgical anesthesia when given EX (94%) or KX (18%) than were other strains. In all strains except C57BL/6NCrl mice, females were more likely to reach surgical anesthesia than males. Several mice experienced an adverse hyperexcitement response during induction, with BALB/cJ (79%) and NU/J (87%) mice given EX significantly more likely than other strains to experience hyperexcitement. EX and KX protocols had no overall differences in lowest respiration rate, lowest systolic blood pressure, lowest rectal temperature, or levels of acidosis, although the lowest heart rates were significantly higher with EX, indicating that EX and KX have similar safety profiles. Thus, EX and KX administration were associated with several significant physiologic differences when comparing sexes or individual strains. Our results indicate that EX is an equally effective sedative and a more effective surgical anesthetic than KX; however, EX is only recommended for invasive procedures in C57BL/6 mice due to the high rate of hyper-excitement and inconsistent surgical depth seen in other strains. Further study is needed to optimize EX for use in multiple mouse strains.

Different Reactions of Zebra Finches and Bengalese Finches to a Three-Component Mixture of Anesthetics.

Kawai et al. (2011) recently introduced a mixture of three anesthetic agents (here called MMB) that has an effect similar to ketamine/xylazine in mice, which might allow more effective reaction to changes in the animal condition, as an antagonist is available, and which can be used without license for handling narcotic drugs. Using Kawai's study as a baseline, we tested whether this anesthesia and its antagonist can also be used in avian studies. In the present study, we used two species, the zebra finch and the Bengalese finch, of the avian family Estrildidae. In zebra finches, anesthesia effects similar to the use of ketamine/xylazine and to those obtained in mice can be reached by the use of MMB if a higher dose is applied. MMB leads to more variable anesthesia, but has the advantage of a longer time window of deep anesthesia. An antagonist to one component of MMB reduced the awaking time, but was not as effective as in mice. For Bengalese finches, MMB cannot be generally recommended because of difficult handling and high mortality rate when used without antagonist, but could be used for perfusions instead of pentobarbital.

Efficacy comparison of intraperitoneal anaesthesia and post-operative analgesia regimens in laboratory rats.

INTRODUCTION: Effective and safe anesthesia for rodents has long been a leading concern among biomedical researchers. Intraperitoneal injection constitutes an alternative to inhalant anesthesia. PURPOSE: The aim of this study was to identify a safe, reliable, and effective anesthesia and postoperative analgesia protocol for laboratory rats exposed to painful procedures. MATERIAL AND METHODS: Twenty-seven female Wistar rats in an ongoing study that required surgery were randomized into groups for three different intraperitoneal anesthesia protocols and three different analgesia regimens. The anesthesia groups were (1) medetomidine + ketamine (MK), (2) ketamine + xylacine (KX), and (3) fentanyl + medetomidine (FM). Three analgesia groups were equally distributed among the anesthesia groups: (1) local mepivacaine + oral ibuprofen (MI), (2) oral tramadol + oral ibuprofen (TI), and (3) local tramadol + oral tramadol + + oral ibuprofen (TTI). A core was assigned to measure anesthesia (0-3) and analgesia (0-2) effectiveness; the lower the score, the more effective the treatment. RESULTS: The mean MK score was 0.44 versus 2.00 for FM and 2.33 for KX. Mean score for analgesia on the first postoperative day was TTI (4.66) TI (9.13), and MI (10.14). Mean score 48 hours after surgery was TTI (3.4), TI (6.71), and MI (9.5). These differences were statistically significant. CONCLUSION: MK was shown to be a reliable, safe, and effective method of anesthesia. The TTI analgesia regimen is strongly recommended in light of these results.

ORAL HALOPERIDOL PREMEDICATION TO REDUCE CAPTURE STRESS PRIOR TO XYLAZINE-KETAMINE ANESTHESIA IN CAPTIVE SPOTTED DEER (AXIS AXIS).

A prospective clinical trial was performed to evaluate the efficacy of haloperidol premedication prior to xylazine-ketamine anesthesia with a goal of reducing capture stress in adult male captive spotted deer (Axis axis). On the morning of the study, deer were fed a banana either containing haloperidol tablets (1 mg/kg) (haloperidol group, n = 10) or without haloperidol (placebo group, n = 10). Six hours postadministration, xylazine (3 mg/kg) and ketamine (2 mg/kg) was administered intramuscularly via a dart. Rectal temperature, heart rate, respiratory rate, and SpO2 (percent hemoglobin saturation) were recorded at 5-min intervals. Blood gas analysis was performed at time 0 (venous blood) and 10 and 20 min (arterial blood) postinduction. Serum cortisol was determined from venous blood (35 min postinduction), following which yohimbine was administered at a dose of 0.15 mg/kg intramuscular and 0.15 mg/kg intravenous. Statistical analysis of repeated measures data was performed with a two-way analysis of variance. Paired data were analyzed with a Wilcoxon rank-sum test (categorical data) or a paired t-test (continuous data). Significance was set at P ≤ 0.05, and results were expressed as mean ± SEM. There was no significant difference in induction time or recovery time between treatment groups. Rectal temperature and heart rate were significantly lower in the haloperidol group. Both groups demonstrated acidosis with venous pH being significantly lower in the placebo group when compared to the haloperidol group. Serum cortisol and arterial plasma lactate were lower in the haloperidol group indicative of reduced stress and physical exertion. Haloperidol premedication proved to be beneficial in reducing capture stress, when administered prior to xylazine-ketamine anesthesia, in spotted deer.

Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia.

This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 µg/kg xylazine or 0.875 µg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed-ranked test with p < .05 considered significant. Elimination half-lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady-state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.

α2-Adrenoceptor agonist induces peripheral antinociception via the endocannabinoid system.

BACKGROUND: Xylazine is an α2 adrenoceptor agonist that is extensively used in veterinary medicine and animal experimentation procedures to produce analgesia, sedation and muscle relaxation without causing general anesthesia. Considering the lack of knowledge of the mechanisms involved in peripheral antinociception induced by xylazine and the potential interactions between the adrenergic and endocannabinoid systems, the present study investigated the contribution of the latter system in the mechanism of xylazine. METHODS: The rat paw pressure test, in which hyperalgesia was induced by the intraplantar injection of prostaglandin E2, was performed. RESULTS: Xylazine administered via an intraplantar injection (25, 50 and 100 µg) induced a peripheral antinociceptive effect against prostaglandin E2 (2 µg)-induced hyperalgesia. This effect was blocked by treatment with the selective CB1 cannabinoid antagonist AM251 (20, 40 and 80 µg) but not by the selective CB2 cannabinoid antagonist AM630 (100 µg). The anandamide reuptake inhibitor VDM11 (2.5 µg) intensified the peripheral antinociceptive effect of a submaximal dose of xylazine (25 µg), and the inhibitor of endocannabinoid enzymatic hydrolysis, MAFP (0.5 µg), showed a tendency towards this same effect. In addition, liquid-chromatography mass spectrometric analysis indicated that xylazine (100 µg) treatment was associated with an increase in anandamide levels in the rat paws treated with PGE2. CONCLUSIONS: The present results provides evidence that the peripheral antinociceptive effect of the α2 adrenoceptor agonist xylazine probably results from anandamide release and subsequent CB1 cannabinoid receptor activation.