Search

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 α 2 -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., (© 2024 EVJ Ltd.)

Chickens ( Gallus gallus domesticus ) are commonly used for research, food production, show, and companionship. Sedation is often necessary for sample collection, imaging, or treatment. Dexmedetomidine has been previously used to sedate birds, often with other sedatives. Butorphanol tartrate, a Schedule IV controlled substance, is commonly used but presents regulatory challenges. Nalbuphine hydrochloride, an opioid with similar receptor affinity to butorphanol, has potential as a noncontrolled alternative. Although information regarding nalbuphine use in birds is limited, its noncontrolled status makes it more accessible. The purpose of this study was to determine the effective dose to produce sedation in 50% (ED 50 ) of patients and to estimate the calculated effective dose of dexmedetomidine in combination with either butorphanol (DexBut) or nalbuphine (DexNal) in domestic hens to sedate 99% of patients (ED 99 ). Eighteen 33-week-old laying Buff Orpington hens were divided into 2 groups: one receiving DexBut (n = 9) and the second receiving DexNal (n = 9). Each hen was sedated with varying doses of intramuscular dexmedetomidine with a constant dose of either 2 mg/kg IM butorphanol or 12.5 mg/kg IM nalbuphine by an up-and-down design. Sedation was determined using a clinically applicable scoring system. The ED 50 values of dexmedetomidine with 2 mg/kg IM of butorphanol, calculated by both the up-and-down method and logistic regression, were 38 and 49 µg/kg, respectively, while the ED 50 values of dexmedetomidine in combination with 12.5 mg/kg IM of nalbuphine were 19 and 18 µg/kg, respectively. The estimated dexmedetomidine ED 99 values with butorphanol or nalbuphine were 51 and 19 µg/kg, respectively. Multiple chickens in both groups exhibited open-mouth breathing and comb pallor but no lasting morbidity or mortality occurred. Combinations of DexBut or DexNal should be considered for sedation of domestic chickens.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk., (© Wildlife Disease Association 2024.)

Objective: To evaluate if opioid-induced behavioral effects, such as sedation, can be detected using a shuttle box experimental apparatus and whether thermal preference following noxious stimulation using mustard oil is reversed by morphine administration in fish., Methods: 5 goldfish (Carassius auratus) underwent 2 randomized blinded experimental trials, with a crossover study design. First, opioid effects were tested in a shuttle box without painful stimulus. Fish were injected 5 days apart with butorphanol at 0.4 or 10 mg/kg, morphine at 5 or 10 mg/kg, or saline IM. After 30 minutes, each fish was placed in a shuttle box for 2 hours with a temperature gradient of 26 to 28 °C. Temperature preference, time spent immobile, and swimming velocity were assessed. The second trial consisted of cutaneous noxious stimulation using mustard oil immersion for 5 minutes followed by an assessment of thermal preference for 4 minutes in the shuttle box after either morphine at 10 mg/kg or saline IM injections. Linear mixed models were used to compare treatment groups., Results: Before noxious stimulation, a low dose of morphine caused sedation compared with control group and high-dose morphine and butorphanol treatments. Immersion in mustard oil caused fish to spend more time in the cold area in the control group. Morphine administration reversed this pattern., Conclusions: The sedative and analgesic effects of opioids were detected through this model., Clinical Relevance: The shuttle box model could be used to assess the analgesic effects of other opioids in goldfish while reducing biases associated with the sedative and stimulatory effects of these drugs.

Administration of butorphanol, azaperone, and medetomidine (BAM) for immobilization of black howler monkeys ( Alouatta pigra ) has not been previously reported. In this observational study, 0.02 ml/kg of compounded BAM (butorphanol 27.3 mg/ml, azaperone 9.1 mg/ml, medetomidine 10.9 mg/ml) was administered IM in 10 captive black howler monkeys. Time to immobilization was recorded, an arterial blood gas performed, and at 5-min intervals, HR, RR, oscillometric arterial blood pressure, SPO 2, and rectal temperature were measured. Naltrexone and atipamezole were administered IM at procedure completion and recovery times were recorded. If invasive procedures such as surgery were necessary and additional drugs needed, further data from that individual was removed from data analysis. Final BAM dosages were 0.55 ± 0.12 mg/kg butorphanol, 0.19 ± 0.04 mg/kg azaperone, and 0.22 ± 0.05 mg/kg medetomidine. Nine of 10 monkeys achieved sedation allowing for physical exam, venipuncture, and tuberculin skin testing within 4 ± 2 min. No monkeys reached a plane of immobilization allowing for intubation. Physiologic variables were acceptable for this species. Hypoxemia (SPO 2 < 95%) was observed in three monkeys via pulse oximetry, and normoxemia was observed on arterial blood gas. Recovery was smooth and rapid. Therefore, BAM is a viable option for noninvasive procedures or as a premedication prior to induction of anesthesia in black howler monkeys.

Twenty lesser chevrotains ( Tragulus sp.), 10 males and 10 females, were anesthetized with a combination of butorphanol-midazolam-medetomidine (BMidM), to assess the efficacy of this protocol for short procedures in this genus. The animals received BMidM (0.32, 0.06, 0.15 mg/kg, respectively) intramuscularly via hand injection. Physiological variables were recorded once the animals reached a working depth of anesthesia that lasted 30 min (range 12-60 min). At the end of the procedure, medetomidine and butorphanol were antagonized with atipamezole (0.75 mg/kg) and naltrexone (0.3 mg/kg) intramuscularly, respectively. Induction and recovery were 9.4 ± 4.0 min and 10.2 ± 4.1 min, respectively. Supplementation with isoflurane via face mask was required in five animals to reach light anesthesia. Times to reach the various stages of anesthesia were compared between sexes. There was no difference between males and females reaching the different stages of anesthesia, except for the time required to reach the ambulatory stage, in which females took a significantly longer time (11.8 min vs 7.8 min for the males) to stand after the injection of the antagonists ( P = 0.02). Heart rate, respiratory rate, rectal temperature, and peripheral hemoglobin oxygen saturation were similar between sexes and stable throughout the procedure. At the dosage tested BMidM was a reliable and safe protocol for short, minimally invasive procedures in lesser chevrotains with a fast induction and smooth recovery without complications.

Objective: To compare the effects of intranasal (IN) and intramuscular (IM) midazolam-butorphanol-ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits., Study Design: Prospective, randomized, crossover experimental study., Animals: Fourteen male New Zealand White rabbits, aged 1-2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation)., Methods: Rabbits were administered midazolam (1 mg kg -1 ), butorphanol (1.5 mg kg -1 ) and ketamine (5 mg kg -1 ) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (f R ), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO 2 ) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded., Results: Drug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), f R (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO 2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points., Conclusions and Clinical Relevance: The combination of midazolam-butorphanol-ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam-tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p = .301) and TS (p = .445). Furthermore, there were no significant changes observed in the IOP (p = .472) and TS (p = .348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p = .0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p < .0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS., (© 2024 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The decontamination process for plumage-contaminated wild birds, such as those affected by oil spills, is lengthy and involves manual restraint and manipulation of all body parts. Birds commonly react to this in ways that suggest they are extremely stressed (eg, struggling, vocalizing). We proposed to reduce stress during the wash process using sedation and hypothesized that the use of sedation would not negatively impact survival. Contaminated birds in need of washing were randomly selected to be either sedated (butorphanol 2 mg/kg IM + midazolam 1 mg/kg IM and flumazenil 0.1 mg/kg IM for reversal) or not sedated at 3 US rehabilitation centers over the course of 1 year. Response to sedation was rated on a scale of 0-4 with 0 as no effect to 4 as excessively sedate. Data such as cloacal temperatures at various time points, lengths of various portions of the wash process, preening behavior in the drying pen, and disposition were collected. No statistical differences were found between sedated and nonsedated birds for any of the data points collected, including survival. There was a significant association between birds with higher cloacal temperatures in the drying pen and with birds held longer in the drying pen with improved survival; however, these findings were unrelated to whether the birds were sedated. Our findings show that sedation with butorphanol 2 mg/ kg IM and midazolam 1 mg/kg IM reversed with flumazenil 0.1 mg/kg IM can be used during the wash process for wild birds without adverse effects. Careful attention must be given to heat support for all birds while drying to prevent hypothermia.

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 μM and 8 μM) (OA + LPS + 4 μM and OA + LPS + 8 μM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment., (© 2024. The Author(s).)

Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. "Balanced anesthesia" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.

Background: The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied., Aim: To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane., Methods: Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A p < 0.05 was considered statistically significant., Results: The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m 2 : p < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm 5 /m 2 : p = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide., Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended., Competing Interests: The authors declare that there is no conflict of interest.

This article reports on respiratory function in white rhinoceros (Ceratotherium simum) immobilized with etorphine-azaperone and the changes induced by butorphanol administration as part of a multifaceted crossover study that also investigated the effects of etorphine or etorphine-butorphanol treatments. Six male white rhinoceros underwent two immobilizations by using 1) etorphine-azaperone and 2) etorphine-azaperone-butorphanol. Starting 10 min after recumbency, arterial blood gases, limb muscle tremors, expired minute ventilation, and respiratory rate were evaluated at 5-min intervals for 25 min. Alveolar to arterial oxygen gradient, expected respiratory minute volume, oxygen consumption, and carbon dioxide production were calculated. Etorphine-azaperone administration resulted in hypoxemia and hypercapnia, with increases in alveolar to arterial oxygen gradient, oxygen consumption, and carbon dioxide production, and a decrease in expired minute ventilation. Muscle tremors were also observed. Intravenous butorphanol administration in etorphine-azaperone-immobilized white rhinoceros resulted in less hypoxemia and hypercapnia; a decrease in oxygen consumption, carbon dioxide production, and expired minute ventilation; and no change in the alveolar to arterial oxygen gradient and rate of breathing. We show that the immobilization of white rhinoceros with etorphine-azaperone results in hypoxemia and hypercapnia and that the subsequent intravenous administration of butorphanol improves both arterial blood oxygen and carbon dioxide partial pressures., (© Wildlife Disease Association 2024.)

Butorphanol is a synthetic opioid analgesic medication that is primarily used for the management of pain. Butorphanol may have an inhibitory effect on androgen biosynthesis and metabolism in rat immature Leydig cells. The objective of this study was to investigate the influence of butorphanol on androgen secretion by rat Leydig cells isolated from the 35-day-old male rats. Rat Leydig cells were cultured with 0.5-50 μM butorphanol for 3 h in vitro . Butorphanol at 5 and 50 μM significantly inhibited androgen secretion in immature Leydig cells. At 50 μM, butorphanol also blocked the effects of luteinizing hormone (LH) and 8bromo-cAMP-stimulated androgen secretion and 22R-hydroxycholesterol- and pregnenolone-mediated androgen production. Further analysis of the results showed that butorphanol downregulated the expression of genes involved in androgen production, including Lhcgr (LH receptor), Cyp11a1 (cholesterol side-chain cleavage enzyme), Srd5a1 (5α-reductase 1), and Akr1c14 (3α-hydroxysteroid dehydrogenase). Additionally, butorphanol directly inhibited HSD3B1 (3β-hydroxysteroid dehydrogenase 1) and SRD5A1 activity. In conclusion, butorphanol may have side effects of inhibiting androgen biosynthesis and metabolism in Leydig cells., Competing Interests: All authors declare that they have no conflict of interest.

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics., (© 2024. The Author(s).)

Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer ( Rangifer tarandus ) in Minnesota using a completely reversible immobilization protocol. Reindeer were immobilized with butorphanol (0.23-0.32 mg/kg), midazolam (0.23-0.32 mg/kg), and medetomidine (0.15 mg/kg) (BMM) via IM dart. Induction time (IT), recumbency time (DT), and recovery time (RT) were recorded. Temperature (T), respiratory rate (RR), pulse rate (PR), pulse oximetry (SpO 2 ), arterial blood gas values including oxygen (PaO 2 ), and carbon dioxide (PaCO 2 ) tensions and lactate (Lac) were recorded preoxygen supplementation and 15 min postoxygen supplementation. Reversal was done using naltrexone (2.3-3.0 mg/kg), flumazenil (0.008-0.01 mg/kg) and atipamezole (0.62-0.78 mg/kg) (NFA) IM, limiting recumbency to 1 h. Median IT, DT, and RT were 5 min, 46 min, and 7 min, respectively. SpO 2 (92 to 99%, P = 0.125), PaO 2 (45.5 to 97 mmHg, P = 0.25), and PaCO 2 (46.5 to 54.6 mmHg, P = 0.25) all increased, whereas Lac (3.02 to 1.93 mmol/L, P = 0.25) decreased between baseline and 15 min postoxygen supplementation, without statistical significance. BMM immobilization, and reversal with NFA provided rapid and effective immobilization and recovery, respectively. Oxygen supplementation mitigated hypoxemia in all reindeer.

The purpose of this study was to assess antinociception and correlation of antinociception and hypothermic effects after intravenous opioids in dogs. Nine healthy male Beagles were enrolled in the study. They were acclimated to a thermal nociceptive device, then received three IV treatments (saline, butorphanol 0.4 mg/kg and methadone 0.5 mg/kg) in a randomized complete block design. Rectal temperature and thermal withdrawals were assessed prior to and 0.5-6 h after drug administration. One dog was excluded due to lack of withdrawal to thermal stimuli. Rectal temperatures were not significantly different between treatments at time 0, but significantly decreased from 0.5 to 5 h for both opioids compared to saline. Withdrawals were significantly decreased, compared to saline, from 0.5 to 4 h for butorphanol and 0.5-5 h for methadone. A significant (p = .0005) and moderate (R 2  = .43) correlation between antinociception and hypothermia occurred. Based on these data, intravenous butorphanol (0.4 mg/kg) and methadone (0.5 mg/kg) provided 4 and 5 h of antinociception, respectively. Opioid hypothermia can serve as an easy, noninvasive and humane manner for preclinical assessment of opioid antinociception in dogs prior to evaluation in clinical trials. This is a major refinement in animal welfare for assessing novel opioids, opioid doses and dose intervals in dogs., (© 2023 John Wiley & Sons Ltd.)

Immobilization kits including butorphanol-azaperone-medetomidine (BAM) and nalbuphine-azaperone-medetomidine can provide effective, safe, and easy-to-use protocols in bears. Nalbuphine-azaperone-medetomidine is not commercially available but may be useful for wildlife agencies because it does not contain controlled substances. This study directly compared BAM to nalbuphine-azaperone-medetomidine immobilization in 10 juvenile healthy black bears (10 mo old; four females, six males) undergoing prerelease examinations after rehabilitation. Bears were immobilized via remote delivery of 1 mL of BAM (n=5) or nalbuphine-azaperone-medetomidine (n=5) intramuscularly in the shoulder during December (randomized, blinded trial). Bears were intubated, monitored with an electrocardiogram, pulse oximeter, capnograph, noninvasive blood pressure cuff, and rectal thermometer, and underwent physical examination, sample collection, morphometrics, and ear-tag placement. Induction, physiologic, and recovery parameters were recorded, including arterial blood gas analysis. The anesthetic agents were antagonized with atipamezole and naltrexone. There were no differences between protocols in induction or recovery times. There were no differences between protocols in heart rate, respiratory rate, temperature, oxygen saturation, end-tidal CO2, mean arterial pressure, or blood gas analysis or any differences between male and female bears in any parameters. Bears were hypertensive and normoxemic with low oxygen saturation via pulse oximeter, but all recovered smoothly and were released within 2 h of recovery. This study supports that nalbuphine-azaperone-medetomidine is clini-cally as safe and effective as BAM in American black bears., (© Wildlife Disease Association 2024.)

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint., (© Wildlife Disease Association 2024.)

Zoo-managed adult African painted dogs ( Lycaon pictus ; n = 17) were anesthetized with mean dosages of dexmedetomidine 5 µg/kg, ketamine 1.93 mg/kg, butorphanol 0.2 mg/kg, and midazolam 0.15 mg/kg IM. Times to induction milestones (mean ± SD or median [range]) were initial effects at 2 min (1-4 min), recumbency at 3.2 ± 1.1 min, and intubation at 11.6 ± 1.3 min. Two dogs required isoflurane supplementation for intubation. Anesthesia was antagonized with mean dosages of atipamezole 0.05 mg/kg IM, naltrexone 0.2 mg/kg IM, and flumazenil 0.01 mg/kg IV. Times from antagonist administration to recovery milestones were extubation at 3.9 ± 1.5 min, control of head at 7.6 ± 2.5 min, sternal positioning at 8.8 ± 2.3 min, and standing at 12.1 ± 3.5 min. Animals were judged ready for reunification with conspecifics at 41.5 min (28-127 min), and reunification occurred at 62.1 ± 35.2 min. Paired arterial blood gas samples were obtained ( n = 13). There was a significant decrease in temperature and blood pressure and increase in pO 2 , BEecf, and HCO 3 - ( P < 0.05). Decreased respiratory rate with hypercapnia was occasionally observed. This protocol provided consistent anesthesia using a low dose α-2 agonist and permitted quick pack reunification.

Sable antelope ( Hippotragus niger ), a large, dominant species, often require chemical immobilization for captive management. Despite several recorded protocols, limited objective or subjective data are available to guide chemical immobilization of this species. This study retrospectively compared immobilization drug combinations of carfentanil-xylazine (CX), thiafentanil-xylazine (TX), etorphine-xylazine (EX), carfentanil-acepromazine (CA), and butorphanol-azaperone-medetomidine (BAM) for healthy sable antelope at one institution. Clinically applicable physiologic measures, subjective ratings, and timing of anesthetic milestones of 161 events for 107 individuals revealed the following statistically significant findings ( P < 0.05). Induction ratings were best for TX, highest degree of muscle relaxation occurred with BAM and TX, and anesthetic ratings were best for TX and EX. Time to recovery was longest and complications 2.56 times more likely with CX. Time to recumbency was shortest in TX. Heart rate was highest in CA and lowest in BAM. For immobilization procedures, this study suggests TX would be the preferred combination for H. niger . However, all drug combinations evaluated can be used successfully to immobilize H. niger, and certain combinations may be situationally preferred based on desired muscle relaxation, expected induction or recovery times, or anticipated procedure length.

Background: This study aimed to compare the sedative and cardiopulmonary effects of intranasal (IN) administration of dexmedetomidine-butorphanol (DB) and midazolam-butorphanol (MB) combinations in New Zealand white rabbits., Methods: Eight New Zealand white rabbits were sedated by IN administration of a combination of 0.1 mg/kg dexmedetomidine and 0.4 mg/kg butorphanol (DB treatment) and 2 mg/kg midazolam and 0.4 mg/kg butorphanol (MB treatment). The electrocardiogram, pulse rate (PR), respiratory frequency (f R ), arterial haemoglobin oxygen saturation (SpO 2 ), fraction of expired carbon dioxide (EtCO 2 ), rectal temperature (RT), noninvasive mean arterial pressure (MAP), noninvasive systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) were recorded. The onset of sedation, duration of sedation and sedation score (SS) were also noted., Results: There were no significant differences in the EtCO 2 , RT, MAP, SAP and DAP measurements between treatments. The PR significantly decreased in DB compared with MB over time (p = 0.001). Compared with baseline, SpO 2 decreased over time in both treatments. The SS was significantly elevated over time in DB compared with MB (p = 0.002)., Limitations: No pharmacokinetic information was available for either treatment, so the findings should be interpreted cautiously., Conclusions: IN DB provides more effective sedation than MB, but cardiopulmonary impairment was observed in both treatments., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Cardiovascular disease is a frequent cause of death in the critically endangered Vancouver Island marmots ( Marmota vancouverensis ). This warrants the use of anesthetic protocols with minimal cardiovascular adverse effects. In this study, 12 adult male woodchucks ( Marmota monax ) were used as models for Vancouver Island marmots. The objective was to compare the physiological effects of two premedication protocols during induction and maintenance of anesthesia with sevoflurane. The two premedications were ketamine 10 mg/kg and midazolam 0.5 mg/kg (KM) or ketamine 10 mg/kg, midazolam 0.5 mg/kg, and butorphanol 1.0 mg/kg (KMB), administered intramuscularly prior to mask induction. Each marmot underwent three anesthetic events and protocols were assigned using a blinded randomized crossover design. Heart rate, respiratory rate, oxygen saturation, and body temperature were recorded throughout, and blood gases were assessed following induction. Resistance to induction was scored and time to induction was recorded. Although mask induction with sevoflurane was successful in all events (mean induction time of 2.1 min), KMB premedication resulted in a faster induction (mean induction time reduced by 1.2 ± 0.3 min) and lower resistance scores. Both protocols resulted in significant cardiovascular and respiratory depression; however, animals that received KMB were more hypercapnic than KM by 8.8 ± 2.8 mm Hg ( P = 0.03) (mean venous partial pressure of carbon dioxide [PvCO2] for all: 79.9 mm Hg). In conclusion, if shorter induction times are desired, KMB premedication is preferred. However, cardiorespiratory variables including blood pressure should be monitored, and endotracheal intubation is recommended to allow for ETCO2 monitoring and provision of intermittent positive pressure ventilation.

We chemically immobilized a free-ranging moose subspecies, Shiras moose (Alces alces shirasi), using a combination of butorphanol (27.3 mg/mL), azaperone (9.1 mg/mL), and medetomidine (10.9 mg/mL). Ground and helicopter darting with fixed doses of 2 mL and 3 mL, respectively, safely immobilized 13 individuals in Wyoming, USA., (© Wildlife Disease Association 2023.)

Objective: To determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs., Study Design: Prospective, blinded, randomized clinical trial., Animals: A total of 116 client-owned healthy dogs undergoing elective surgery., Methods: Dogs were randomly allocated one of four groups: group M, medetomidine 5 μg kg -1 ; group B, butorphanol 0.2 mg kg -1 ; group MB, medetomidine 5 μg kg -1 and butorphanol 0.2 mg kg -1 ; or group MBK, medetomidine 5 μg kg -1 , butorphanol 0.2 mg kg -1 and ketamine 1 mg kg -1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg -1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test., Results: Sedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks. Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg -1 ) than in group M (2.6 ± 0.6 mg kg -1 ). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg -1 ) and MBK (0.9 ± 0.8 mg kg -1 ), both groups required significantly less propofol than group M., Conclusion and Clinical Relevance: Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The use of general anesthesia in dromedary camels is constrained by risks related to decubitus. Caudal epidural analgesia is an alternative convenient technique providing loco-regional analgesia for numerous invasive and noninvasive painful conditions. Lidocaine is probably the most commonly used local anesthetic in clinical practice, but has a relatively short duration and may not provide significant long term analgesic benefits. Epidural administration of an opioid-local anesthetic mixture would improve the quality and length of analgesia and minimizes the adverse motor effects provoked by local anesthetics. Butorphanol (potent agonist-antagonist opioid) has been used to improve the duration of epidural analgesia in some animal species, but not in camels. Therefore, our purpose was to investigate the onset and duration of analgesia as well as the clinical and hemato-biochemical effects produced by the epidural administration of butorphanol (0.04 mg/kg), lidocaine (0.22 mg/ kg), and butorphanol-lidocaine (0.04 mg/kg-0.22 mg/ kg) mixture in nine adult dromedary camels in a crossover experimental study., Results: The onset of analgesia was not statistically different between lidocaine (6.5 ± 2.3 min) and butorphanol-lidocaine (7.3 ± 1.5 min) combination. Delayed onset of analgesia was reported after butorphanol administration (14.7 ± 3.5 min). Butorphanol-lidocaine combination produced marked longer duration (175 ± 8.7 min) than lidocaine (55 ± 6.8 min) and butorphanol (158 ± 5.3 min). Mild ataxia was observed in the butorphanol-lidocaine and lidocaine treated animals and slight sedation was reported after butorphanol and butorphanol-lidocaine administration. A transient significant increase in the glucose levels was recorded after all treatments., Conclusions: Epidural administration of butorphanol augments the analgesic effects and duration of lidocaine with minimal adverse effects., (© 2023. The Author(s).)

Background: Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine., Methods: A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis., Results: The ED50 (mean [95% confidence interval (CI)]) of the dose of intravenous butorphanol infusion for preventing moderate to severe pruritus was lower in Group P + B (3.29 µg/kg/min [3.25-3.34 µg/kg/min]) than in Group B (3.57 µg/kg/min [3.47-3.67 µg/kg/min]) ( p  < 0.05)., Conclusions: Under the conditions of the present study, a prophylactic use of 0.25 mg palonosetron reduced the ED50 of prophylactic infusion of butorphanol by approximately 8% to achieve a satisfactory antipruritic effect after epidural morphine for post-caesarean analgesia.

Objective: To evaluate the heart rate (HR) and systemic arterial pressure (sAP) effects, and propofol induction dose requirements in healthy dogs administered propofol with or without guaifenesin for the induction of anesthesia., Study Design: Prospective blinded crossover experimental study., Animals: A total of 10 healthy adult female Beagle dogs., Methods: Dogs were premedicated with intravenous (IV) butorphanol (0.4 mg kg -1 ) and administered guaifenesin 5% at 50 mg kg -1 (treatment G50), 100 mg kg -1 (treatment G100) or saline (treatment saline) IV prior to anesthetic induction with propofol. HR, invasive sAP and respiratory rate (f R ) were recorded after butorphanol administration, after guaifenesin administration and after propofol and endotracheal intubation. Propofol doses for intubation were recorded. Repeated measures analysis of variance (anova) was used to determine differences in propofol dose requirements among treatments, and differences in cardiopulmonary values over time and among treatments with p < 0.05 considered statistically significant., Results: Propofol doses (mean ± standard deviation) for treatments saline, G50 and G100 were 3.3 ± 1.0, 2.7 ± 0.7 and 2.1 ± 0.8 mg kg -1 , respectively. Propofol administered was significantly lower in treatment G100 than in treatment saline (p = 0.04). In treatments G50 and G100, HR increased following induction of anesthesia and intubation compared with baseline measurements. HR was higher in treatment G100 than in treatments G50 and saline following induction of anesthesia. In all treatments, sAP decreased following intubation compared with baseline values. There were no significant differences in sAP among treatments. f R was lower following intubation than baseline and post co-induction values and did not differ significantly among treatments., Conclusions and Clinical Relevance: When administered as a co-induction agent in dogs, guaifenesin reduced propofol requirements for tracheal intubation. HR increased and sAP and f R decreased, but mean values remained clinically acceptable., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. All rights reserved.)

Background: Weddell seals (Leptonychotes weddellii) are a well-studied species of phocid with an apparent sensitivity to immobilising agents. Mortality as high as 31% has been reported during field immobilisation. This study investigated the use of a benzodiazepine in combination with an opioid agonist/antagonist for sedation in Weddell seal pups as part of a physiological study., Methods: During the 2017 and 2019 Antarctic pupping seasons, 18 Weddell seal pups were sedated by intramuscular administration of a combination of midazolam and butorphanol or intravenous midazolam alone. Individuals were sedated at 1, 3, 5 and 7 weeks of age. Naltrexone and flumazenil were used to reverse sedation. The combination was 100% effective in providing appropriate sedation for the intended procedures., Results: Analyses were performed to investigate relationships between dose administered, age, individual reactions, adverse effects and changes in dive physiology. Transient apnoea (10-60 seconds) was the most frequently observed adverse effect. No sedation-associated morbidity or mortality occurred., Limitations: The sample size is small and there is no pharmacokinetic information for either sedative or reversal in phocid species., Conclusions: The combination of midazolam (0.2-0.3 mg/kg) and butorphanol (0.1-0.2 mg/kg) provided safe and effective sedation, with reversible effects, in Weddell seal pups., (© 2022 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Objective: To evaluate 2 doses of alfaxalone on cardiopulmonary parameters, temperature, sedation, endotracheal intubation, the incidence of muscle tremors, and radiographic positioning in Quaker parrots previously administered intranasal midazolam and butorphanol., Animals: 10 healthy adult Quaker parrots (male = 5; female = 5)., Procedures: A randomized, masked, crossover study was conducted where birds received midazolam (2 mg/kg) and butorphanol (2 mg/kg) intranasally 15 minutes prior to a low- or high-dose of intramuscular alfaxalone: 2 mg/kg (LDA) or 5 mg/kg (HDA), respectively. Heart (HR) and respiratory rate (RR), cloacal temperature, sedation quality, and ability to position for radiographs were recorded over time. The incidence of muscle tremors and the ability to intubate were recorded. Data were compared to baseline values and between treatments where appropriate. Significance was set at P < .05., Results: There were no significant differences in HR, RR, cloacal temperature, and sedation scores between treatments at any time point. Duration of time from midazolam-butorphanol administration to complete recovery from treatment administration was significantly shorter for LDA when compared to HDA (90 [60 to 195] vs 127.5 [90 to 10] minutes, respectively). Compared to baseline, sedation scores were significantly higher from T = 15 to 60 for LDA and from T = 15 to 75 for HDA. The incidence of muscle tremors was greater in HDA (9/10) than in LDA (7/10). All birds were successfully intubated and positioned for radiographs., Clinical Relevance: The combination of intranasal midazolam-butorphanol and intramuscular alfaxalone at the doses examined was a safe and effective method for sedating Quaker parrots. LDA produced adequate sedation with a shorter time to recovery and with fewer muscle fasciculations when compared to HDA.

Butorphanol, a synthetic opioid, exerts analgesic and anti-inflammatory effects against pathogenic diseases. Butorphanol repressed malignant behaviors of tumor cells. In this study, the role of butorphanol in hepatocellular carcinoma was evaluated. Firstly, hepatocellular carcinoma cells were treated with butorphanol. The results showed that butorphanol decreased cell viability of hepatocellular carcinoma cells. Cell proliferation and metastasis of hepatocellular carcinoma cells were inhibited by butorphanol. Secondly, butorphanol suppressed angiogenesis, and reduced phosphorylation levels of p38 and JNK in hepatocellular carcinoma cells. Thirdly, butorphanol reduced in vivo tumor growth of hepatocellular carcinoma in nude mice. Butorphanol reduced tumor micro-vascular density (MVD) and repressed lung metastasis. In conclusion, butorphanol exerted anti-angiogenic and anti-metastatic effects on hepatocellular carcinoma and induced inactivation of MAPKs signaling., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Objective: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration., Study Design: A randomized, controlled, blinded, clinical trial., Animals: A total of 28 client-owned dogs., Methods: Dogs were premedicated with medetomidine (0.125 mg m -2 ) and butorphanol (0.2 mg kg -1 ) (group MB; n = 14), or medetomidine (0.25 mg m -2 ), butorphanol (0.2 mg kg -1 ) and vatinoxan (5 mg m -2 ) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg -1 ) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg -1 ) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f R ), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe'Sevo) and carbon dioxide (Pe'CO 2 ) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations., Results: At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute -1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f R , Pe'CO 2 , Fe'Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups., Conclusions and Clinical Relevance: In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Chickens ( Gallus gallus domesticus ) often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this species. The objective of this study was to assess the effects of intramuscular alfaxalone and midazolam compared with intramuscular butorphanol and midazolam in chickens. In a complete crossover study, 11 healthy adult hens were randomly administered midazolam 2.5 mg/kg IM combined with either alfaxalone 15 mg/kg IM (AM, n = 11) or butorphanol 3 mg/kg IM (BM, n = 11), with a 35-day washout period between groups. Time to first effects, recumbency, standing, and recovery were recorded. Physiologic parameters and sedation scores were recorded every 5 minutes by 2 blinded investigators. Fifteen minutes after injection, positioning for sham whole body radiographs was attempted. At 30 minutes, flumazenil 0.05 mg/kg IM was administered to all hens. Peak total sedation score was significantly higher for AM compared with BM ( P < 0.001). Mean ± SD or median (range) time to initial effects, recumbency, standing, and recovery in AM and BM were 1.9 ± 0.6 and 2.6 ± 0.9 ( P = 0.02), 3.5 (1.6-7.6) and 4.8 (2.2-13.0) ( P = 0.10), 40.3 (28.0-77.8) and 33.2 (5.2-41.3) ( P = 0.15), and 71.2 (45.7-202.3) and 39.9 (35.9-45.9) minutes ( P = 0.05), respectively. Radiographic positioning was successful in 6 of 11 (54.5%) and 0 of 11 (0%) birds in the AM and BM groups at 15 minutes, respectively. Heart and respiratory rates remained within acceptable clinical limits for all birds. Intramuscular AM resulted in significantly faster onset of sedative effects, significantly longer duration of recumbency, significantly higher peak sedation, and improved success of radiographic positioning compared with intramuscular BM. Intramuscular AM produces clinically effective sedation in chickens without clinically significant cardiorespiratory effects.

This study aimed to identify the possible advantages of administering butorphanol (BUT), associated with ketamine/xylazine (KX) sedation or not, for semen collection using electroejaculation (EE) in rams. Fifteen rams received four treatments in a cross-over design using a 2 × 2 factorial arrangement. The treatments were 1) control; 2) received KX; 3) received BUT; and 4) received both treatments. The responses to the procedures regarding heart rate, respiratory frequency, and rectal temperature were recorded, glucose and creatine kinase were measured, and semen quality was determined. More pulses were required when BUT was administered (P = 0.0067), but rams vocalized fewer times (P = 0.046). The administration of KX also tended to reduce the respiratory frequency (P = 0.068) and rectal temperature (P = 0.089), with no other effects. The administration of BUT reduced the heart rate (P < 0.0001), and there was an interactive effect between the administration of BUT and time on the heart rate (P < 0.0001), respiratory frequency (P = 0.01), and rectal temperature (P = 0.047). The administration of BUT reduced the heart rate increase immediately after EE (P < 0.0001). The respiratory frequency following EE was greater when BUT was administered (P < 0.0001), but the administration of BUT reduced the rectal temperature at the same time (P = 0.002). Glucose concentration was greater when BUT was administered (P < 0.0001). The only significant effect on the ejaculate characteristics was from the interaction between KX and BUT on sperm concentration (P = 0.004). The administration of KX alone increased sperm concentration (P = 0.035), but when BUT was added to KX, sperm concentration decreased (P = 0.002). Moreover, sperm concentration was greater when only BUT was administered than when KX and BUT were administered simultaneously (P = 0.037). The addition of BUT markedly decreased most negative responses more effectively than sedation with KX alone. In conclusion, BUT appears to be an interesting alternative to reduce the welfare concerns raised by the use of EE in rams; however, its possible effects on the ejaculate characteristics when associated with other anesthesia/sedation drugs require further study., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Egyptian fruit bats have gained increasing interest being a natural reservoir for emerging zoonotic viruses. Anaesthesia is often required to allow safe handling of bats. We aimed to compare the sedative and cardiopulmonary effects of two balanced anaesthetic protocols in bats undergoing gonadectomy. Group DK (n = 10) received intramuscular dexmedetomidine (40 µg/kg) and ketamine (7 mg/kg), whereas group DBM (n = 10) received intramuscular dexmedetomidine (40 µg/kg), butorphanol (0.3 mg/kg) and midazolam (0.3 mg/kg). Induction time and cardiopulmonary parameters were recorded. If anaesthetic plan was inadequate, isoflurane was titrated-to-effect. At the end of surgery venous blood gas analysis was performed and atipamezole or atipamezole-flumazenil was administered for timed and scored recovery. In DBM group heart rate and peripheral oxygen saturation were significantly higher (p = 0.001; p = 0.003 respectively), while respiratory rate was significantly lower (p = 0.001). All bats required isoflurane supplementation with no significant differences between groups. Induction and recovery times showed no significant differences. In group DK a better recovery was scored (p = 0.034). Sodium and chloride were significantly higher in DBM group (p = 0.001; p = 0.002 respectively). Both anaesthetic protocols were comparable and can be recommended for minor procedures in bats., (© 2022. The Author(s).)

The aim of this study was to evaluate the postoperative analgesic and antioxidant effects of butorphanol given in the preoperative or early postoperative period. Twenty-seven healthy female dogs undergoing ovariohysterectomy were randomly divided into three groups as before surgery group (BSG, n = 7) received butorphanol 30 min before preanesthetic administration, after surgery group (ASG, n = 10) received butorphanol during the last skin suture and the control group (CG, n = 10) received no butorphanol. Pain was assessed with short form of the Glasgow composite pain scale (CMPS-SF). Serum concentration of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities (GPx) were quantified by spectrophotometric methods to assess oxidative stress status. The pain score increased rapidly at 1 h after surgery and then decreased gradually towards to 24 h in all groups. There was no statistical difference among the groups in terms of CMPS-SF scores (P > 0.05). Serum concentration of MDA was lower in ASG than in BSG and CG from 1 h to 24 h after surgery. Serum activity of GPx was higher in ASG than in BSG and CG from 2 h to 24 h (P < 0.05). Serum activity of SOD was higher in ASG than in BSG and CG from 1 h to 24 h after surgery (P < 0.05). Serum SOD activity at different time points in ASG did not differ compared to preoperative level though it decreased significantly from 1 h onwards both in CT and BSG. The results indicate that single butorphanol administration either before or after the operation might not provide sufficient analgesia, however, it seems that it has antioxidant potential and may protect tissues by reducing oxidative stress when administered early postoperative period following ovariohysterectomy., (Copyright © 2022. Published by Elsevier Inc.)

Rabbits are a common companion animal and research subject and frequently require sedation to facilitate procedures. The objective of this study was to compare the effects of intramuscular butorphanol and midazolam combined with either alfaxalone or ketamine in rabbits. In a complete crossover study, healthy New Zealand white rabbits ( n = 9; age, 6 mo) randomly received midazolam (1 mg/kg IM) and butorphanol (1 mg/kg IM) combined with either alfaxalone (2 mg/kg IM; ABM) or ketamine (5 mg/kg IM; KBM). Time to first effects, recumbency, and standing (recovery) were recorded. Every 5 min during recumbency, an investigator who was blind to treatment group collected serial physiologic parameters and sedation scores. At 5 min after rabbits became recumbent, manipulations were performed to mimic 2-view radiography and a cephalic intravenous catheter was placed. At 30 min after drug injection, flumazenil (0.05 mg/kg IM) was administered for reversal. Food consumption and fecal output were measured for 3 d after each study day. Time to standing and duration of recumbency differed significantly between groups. The median (range) of the total sedation score for ABM was 10 (8 to 10) and for KBM was 10 (6 to 10). Sham radiographs were successful in all rabbits in both groups. Physiologic parameters were not significantly different between groups over time. At 24 h after drug treatment, KBM-treated rabbits showed reduced food intake and both groups showed reduced fecal output. Total sedation scores decreased significantly over time in KBM rabbits ( P < 0.001) but not in ABM rabbits ( P = 1). The duration of recumbency was significantly longer in ABM rabbits than in KBM rabbits. Both protocols produced sufficient sedation for radiograph acquisition without clinically significant adverse effects.

Objectives: The aim of this study was to compare the quality of sedation with three different anaesthetic protocols (alfaxalone combined with butorphanol, methadone or pethidine) administered intramuscularly in cats, and to evaluate the influence of the injection site (between supraspinatus and quadriceps muscles) on the onset and quality of sedation., Methods: A total of 151 cats were selected for this study. Cats were sedated with alfaxalone (3 mg/kg) combined with either butorphanol (0.3 mg/kg; n = 50), methadone (0.3 mg/kg; n = 53) or pethidine (5 mg/kg; n = 48). The combination was injected intramuscularly into the supraspinatus (n = 79) or quadriceps muscle (n = 72). The data included a scoring system for the quality of sedation and physiological parameters, such as heart rate (HR), respiratory rate, body temperature and occurrence of mydriasis, monitored during the first 30 mins of anaesthesia., Results: The opioid associated with alfaxalone influenced the overall sedation score, the degree of myorelaxation, the occurrence of mydriasis and HR. The overall sedation score was poorer with butorphanol than with methadone ( P  = 0.008), and butorphanol induced a lower degree of myorelaxation than methadone ( P  = 0.013). The injection into the supraspinatus showed better qualitative results for sedation and a faster onset time (in about 3 mins) than that into the quadriceps ( P <0.001). HR decreased from baseline ( P <0.001) and over time ( P <0.001), mainly in cats of the butorphanol-supraspinatus and pethidine-quadriceps groups ( P  = 0.004). The occurrence of mydriasis was lower after butorphanol than after methadone and pethidine ( P  = 0.025), while the incidence of side effects did not differ among groups., Conclusions and Relevance: All three protocols provided a good quality of sedation and allowed performing the scheduled procedure. Moreover, the injection into the supraspinatus muscle showed superior results in all the qualitative scores of sedation and quicker onset time than that into the quadriceps muscle.

Background: Visual evoked potentials (VEPs) can provide objective functional assessment of the post-retinal visual pathway. This study compared the effects of sedation (butorphanol and dexmedetomidine) and general anesthesia (propofol and sevoflurane) on pattern and flash VEPs. Dogs (n = 13) underwent sedation or anesthesia and VEPs were obtained from 3 subcutaneous recording electrodes placed on the head (O1, Oz, O2)., Results: Pattern VEPs could only be recorded under sedation and a maximum of 3 peaks were identified (N75, P100, N135). Flash VEPs could be recorded under both sedation and anesthesia and a maximum of 5 peaks were identified (N1, P1, N2, P2, N3). The latency of the N1 peak and the baseline-N1 amplitude were significantly longer under general anesthesia., Conclusion: Visual evoked potentials should be preferentially recorded in dogs sedated with dexmedetomidine and butorphanol, regardless of the stimulus., (© 2022. The Author(s).)

Objective: To determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs., Study Design: Prospective, blinded, Latin square design., Animals: A total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation., Methods: Each dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg -1 ; treatment LDA), high-dose acepromazine (0.04 mg kg -1 ; treatment HDA), low-dose butorphanol (0.2 mg kg -1 ; treatment LDB), high-dose butorphanol (0.4 mg kg -1 ; treatment HDB); and a combination of acepromazine (0.02 mg kg -1 ) with butorphanol (0.2 mg kg -1 ; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg -1 IV over 15 seconds, followed by boluses (0.5 mg kg -1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05)., Results: Propofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg -1 ); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg -1 ). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs)., Conclusions and Clinical Relevance: Although the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To compare ketamine-butorphanol-azaperone-medetomidine (KBAM) to detomidine-etorphine-acepromazine (DEA) for field anesthesia in captive Przewalski horses (Equus przewalskii)., Animals: 10 adult Przewalski horses., Procedures: A prospective randomized crossover trial was conducted. Each horse was immobilized once with KBAM (200 mg ketamine, 109.2 mg butorphanol, 36.4 mg azaperone, and 43.6 mg medetomidine) and once with DEA (40 mg detomidine premedication, followed 20 minutes later by 3.9 to 4.4 mg etorphine and 16 to 18 mg acepromazine). Both protocols were administered by IM remote dart injection with a washout period of 6 months between treatments. Selected cardiorespiratory variables and quality of anesthesia were recorded. Antagonists were administered IM (KBAM, 215 mg atipamezole and 50 mg naltrexone; DEA, 4 mg RX821002 and 100 mg naltrexone)., Results: All horses were anesthetized and recovered uneventfully. Inductions (DEA, 6.8 min; KBAM, 11.6 min; P = 0.04) and recoveries (DEA, 3.2 min; KBAM, 19.6 min; P < 0.01) were faster with DEA compared with KBAM. Quality scores for induction and recovery did not differ between protocols, but maintenance quality was poorer for DEA (P < 0.01). Clinical concerns during DEA immobilizations included apnea, severe hypoxemia (arterial partial pressure of oxygen < 60 mm Hg), muscle rigidity, and tremors. Horses treated with KBAM were moderately hypoxemic, but arterial partial pressures of oxygen were higher compared with DEA (P < 0.01)., Clinical Relevance: Captive Przewalski horses are effectively immobilized with KBAM, and this protocol results in superior muscle relaxation and less marked hypoxemia during the maintenance phase, but slower inductions and recoveries, compared with DEA.

Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)-induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase-3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R-induced viability inhibition, LDH release, cell apoptosis, and increase of caspase-3 activity and expression levels of cleaved caspase-3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen-activated protein kinase (MAPK) signaling in OGD/R-treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R-induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF-1α/VEGF pathways and inactivating the MAPK pathway., (© 2021 John Wiley & Sons, Ltd.)

Background: To the authors' knowledge, the effect of a combination of butorphanol tartrate and detomidine hydrochloride on the laryngeal function and symmetry of the arytenoid cartilages in young Thoroughbred horses has not been examined. Therefore, this study aimed to examine the effects of administration of butorphanol and detomidine on left-to-right rima glottidis ratio (L:R RGR), cross-sectional area of the rima glottidis (CSARG) and grade of laryngeal function of Thoroughbred yearlings examined endoscopically at rest., Methods: Forty-six Thoroughbred yearlings underwent laryngeal video endoscopy, at rest, before and after sedation with butorphanol and detomidine. Three clinicians assigned grades of laryngeal function after reviewing the video recordings. The L:R RGR and CSARG were measured at the point of arytenoid cartilages' maximal abduction. Student's t-test was used to compare the L:R RGR and CSARG. Cohen's kappa (κ) was used to compare the intra- and interobserver agreements. Spearman's rank order was used to assess agreement between CSARG and grade of laryngeal function., Results: Sedation had no effect on L:R RGR and CSARG. Mean intraobserver agreement of grade of laryngeal function of unsedated yearlings was 93.1%, and that of sedated yearlings was 92.9%. Mean interobserver agreement of grade of laryngeal function of unsedated yearlings was 92.8%, and that of sedated yearlings was 92.7%. Correlation between CSARG and laryngeal function grade was significant for both groups (p < 0.001)., Conclusion: Sedating Thoroughbred yearlings with detomidine and butorphanol, before endoscopically examining the larynx, did not significantly affect the grade of laryngeal function., (© 2022 British Veterinary Association.)

Background: Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses., Objectives: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses., Study Design: Retrospective and prospective descriptive studies., Methods: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6-year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamine was given intravenously (iv). Induction and recovery time and quality via a standardised rubric (1 = very poor; 5 = excellent) and visual analogue scale (VAS), need for additional darts, weight tape measurement and serial physiological parameters were recorded. Serial arterial blood gas analysis was performed during recumbency. Following castration, horses were given 0.1 mg/kg bwt atipamezole (25% iv and 75% im) and allowed to recover unaided., Results: Retrospectively, 28 horses were successfully immobilised with BAM™ without a major complication. Prospectively, eight horses were given a median (range) actual BAM TM dose of 0.0143 (0.0127-0.0510) mL/kg bwt. Three of eight horses needed 1, 2 or 5 additional darts. Median (range) time to recumbency was 11 (2-44) minutes. Median (range) induction (n = 4) and recovery (n = 6) scores via rubric and VAS were 5 (4-5) and 5 (5-5) and 92 (86-93) and 98 (92-99) cm, respectively. Four of seven horses were hypoxaemic at ≥1 time point with otherwise acceptable physiological parameters. Following atipamezole, median (range) time to sternal recumbency and standing was 12 (2-18) and 17 (11-52) minutes, respectively (n = 6)., Main Limitations: The sample size was small. Data could not be collected before darting or after recovery. Some data were missing from retrospective analysis., Conclusions: Intramuscular BAM™ with iv ketamine provided chemical restraint suitable for field castration of feral horses with no mortality. Hypoxaemia occurred in the majority of horses., (© 2021 EVJ Ltd.)

A non-narcotic anesthetic combination (Me/Mi/Bu) of medetomidine (Me), midazolam (Mi), and butorphanol (Bu) has been recommended as the injectable anesthesia in mice. An original dose of Me/Mi/Bu (0.3/4.0/5.0 mg/kg) has provided sufficient anesthetic duration of 40-50 min in mice. In addition, atipamezole is available for reversal of Me/Mi/Bu anesthesia. As an adverse effect of Me/Mi/Bu anesthesia, however, severe hypothermia has been also observed in mice. In the present study, we investigated 1) the main agent in Me/Mi/Bu to cause of hypothermia, 2) the effects of the differential doses of atipamezole on hypothermia induced by Me/Mi/Bu anesthesia and on the plasma levels of creatinine phosphokinase and transaminases, and 3) those recommended doses for preventing hypothermia induced by Me/Mi/Bu anesthesia in mice. The results suggested that 1) the α 2 -agonist medetomidine is most likely to induce hypothermia in mice under Me/Mi/Bu anesthesia, 2) the antagonism of atipamezole within proper dose range is effective in promoting the recovery from Me/Mi/Bu-induced hypothermia, and 3) Me/Mi/Bu at the recommended dose of 0.2/6.0/10.0 mg/kg enable to provide anesthetic effects for 40 min and is more considerable to prevent the hypothermia than that at the original dose of 0.3/4.0/5.0 mg/kg.

Objective: To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC ISO ) in cats and to examine the dosage dependence of this effect., Study Design: Randomized, placebo-controlled, crossover experimental study., Animals: A group of six healthy adult male neutered cats., Methods: Cats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg -1 IV bolus followed by 85 μg kg -1 minute -1 for 20 minutes, then 43 μg kg -1 minute -1 for 40 minutes, then 19 μg kg -1 minute -1 ), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MAC ISO was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured., Results: Butorphanol reduced MAC ISO in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control., Conclusions and Clinical Relevance: Butorphanol caused a dosage-dependent MAC ISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aging is an important risk factor for osteoarthritis (OA). Butorphanol is a preoperative sedative and analgesic that possesses anti-inflammatory activity. However, the effect of butorphanol on OA has not been reported. Here we aimed to explore the effect of butorphanol tartrate on the cellular senescence of human chondrocyte-articular (HC-A) cells in response to tumor necrosis factor-α (TNF-α) stimulation. Butorphanol tartrate attenuated the TNF-α-caused cellular senescence of HC-A cells, with decreased positive senescence-associated-β-galactosidase (SA-β-gal) staining and elevated telomerase activity. Butorphanol tartrate prevented TNF-α-caused cell cycle arrest in the G0/G1 phase in HC-A cells and decreased p21 expression. The TNF-α-induced production of interleukin (IL)-6 and IL-8 in HC-A cells were mitigated by butorphanol tartrate. In addition, butorphanol tartrate reduced p-NF-κB p65/total p65 and p-STAT3/STAT3 ratios in HC-A cells cultured with TNF-α. Taken together, butorphanol tartrate protected HC-A cells from TNF-α-caused cellular senescence through inactivation of NF-κB and STAT3. These results imply that butorphanol tartrate might be used as a potential agent for the treatment of aging-related OA.

A high concentration of homocysteine (Hcy) has been recently reported to be closely associated with the development of stroke, which is related to the Hcy-induced blood-brain barrier (BBB) dysfunction. Butorphanol tartrate is a promising analgesic agent that targets the opiate receptor and shows promising protective effects on ischemia/reperfusion injury. The present research proposes to investigate the protective effect of butorphanol tartrate on Hcy-induced BBB disruption to explore the potential application of butorphanol tartrate in treating Hcy-induced stroke. Hcy was utilized to establish both an in vivo animal model and in vitro human brain vascular endothelial cells (HBVECs) injury model. We found that the increased diffusion of sodium fluorescein and Evan's blue, declined expression of Claudin-5, and increased production of interleukin- 6 (IL-6) and tumor necrosis factor-α (TNF-α) were observed in Hcy-treated mice, which were all significantly reversed by butorphanol tartrate. In Hcy-stimulated HBVECs, increased endothelial permeability and reduced expression levels of Claudin-5 and Krüppel-like factor 5 (KLF5) were observed, all of which were dramatically rescued by 2 and 5 µM butorphanol tartrate. Lastly, the protective function of butorphanol tartrate in Hcy-stimulated HBVECs was dramatically abolished by the knockdown of KLF5. Collectively, butorphanol tartrate showed protective effects on Hcy-induced BBB disruption by upregulating the KLF5/Claudin-5 axis.

We describe induction time in six white rhinoceros (Ceratotherium simum) when they received etorphine intramuscularly (IM) or etorphine plus azaperone IM. The median induction time was reduced from 8.9 min for etorphine alone to 6.25 min with azaperone; however, there was no difference in immobilization quality between treatments., (© Wildlife Disease Association 2022.)