Evaluation of general anesthesia protocols for a highly controlled cardiac ischemia-reperfusion model in mice.

BACKGROUND: The aim of our study was to test different anesthetic mixtures in order to identify the most suitable one for a surgical cardiac ischemia-reperfusion model in mice. METHODS: 1) Sixty four mice were submitted to one of the 6 combinations of ketamine or alfaxalone associated to xylazine, medetomidine or midazolam. Depth and quality of anesthesia were evaluated via 5 reflex scores. 2) Impact of analgesic (buprenorphine or butorphanol), anesthesia reversal (with atipamezole) and surgery (cardiac ischemia-reperfusion surgery) have been tested in the selected protocols. 3) infarction size has been measured with TTC (Triphenyl Tetrazolium Chloride) method in mice anesthetized with best protocols. RESULTS: Protocol involving medetomidine induced the longest surgical anesthesia: (median = 120, {interquartile range = 100-125}) min with ketamine and 53 {25-100} min with alfaxalone. Butorphanol substitution with buprenorphine did not alter time-related anesthesia parameters. Atipamezole reversal considerably reduced both recovery and immobilization time (respectively 22 {18-30} min and 98 {88-99} min vs. 55 {40-70} min and 143 {131-149} min, in groups with no reversal, p = 0.001) with no impact on infarction size measurement. CONCLUSION: In this study, the combination alfaxalone/medetomidine/buprenorphine (80/0,3/0,075 mg.kg-1, s.c.) associated with reversal by atipamezole was a reliable anesthetic protocol for murine surgery, particularly for the study of ischemia-reperfusion.

Massive perturbation of sound representations by anesthesia in the auditory brainstem.

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing.

CARDIORESPIRATORY EFFECTS OF VATINOXAN IN BLESBOK (DAMALISCUS PYGARGUS PHILLIPSI) IMMOBILIZED WITH THIAFENTANIL-MEDETOMIDINE.

Combinations of a low dose of opioid, such as thiafentanil, and a high dose of medetomidine, are increasingly being used for immobilization of African ungulates. Both drugs can have undesirable cardiorespiratory effects. In this study we assessed whether vatinoxan, a peripherally acting alpha2-adrenergic receptor antagonist, can be used to alleviate some of these effects without affecting the immobilization quality. Eight healthy, female, boma-confined blesbok (Damaliscus pygargus phillipsi), weighing a mean (SDtion) of 56.8 (4.4) kg, were immobilized twice in a randomized cross-over study with a 2-wk washout period using (1) 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), (2) TM + vatinoxan: 0.5 mg thiafentanil + 1.5 mg medetomidine + 15 mg vatinoxan per milligram medetomidine (total of 22.5 mg, administered intramuscularly at 10 min post recumbency). Heart rate, respiratory rate, rectal temperature, oxygen saturation (SpO2), arterial blood pressure, and sedation scores from 1 to 5 (1 = limited effect; 5 = excessively deep) were measured every 5 min. Arterial blood gases (PaO2 and PaCO2) were measured at 10, 15, 25, and 35 min postrecumbency and the alveolar--arterial oxygen gradient (P[A-a]O2) was calculated. Induction times and immobilization quality did not differ between groups. The heart rate was significantly higher and the mean arterial pressure significantly lower in blesbok after receiving vatinoxan. All animals were hypoxemic and there were no significant differences in the respiratory rates, PaO2, PaCO2, SpO2, or P(A-a)O2 gradients at any time point. Although vatinoxan did not improve respiratory variables and blood oxygenation in these animals, the change in cardiovascular variables may suggest that it improves tissue perfusion, a positive outcome that requires further investigation.

EVALUATION OF A BUTORPHANOL-MIDAZOLAM-MEDETOMIDINE PROTOCOL FOR SHORT PROCEDURES IN LESSER CHEVROTAINS (TRAGULUS SP.).

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.

IMMOBILIZATION OF BLACK HOWLER MONKEYS (ALOUATTA PIGRA) USING BUTORPHANOL, AZAPERONE, MEDETOMIDINE IS SAFE AND EFFECTIVE FOR NONINVASIVE PROCEDURES.

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, SPO2, 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 (SPO2 < 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.

Chemical Immobilization Effects on Cougar (Felis concolor) Movement.

Capturing and handling wildlife is a common practice for both management and research. As telemetry use has become common, the need to capture and chemically immobilize wildlife has increased. Understanding how long the effects of immobilizing agents last after releasing the animal is often poorly understood but needed to ensure that analyses use data that reflect natural behavior. Between 2016 and 2021, 60 cougars (Puma concolor) were chemically immobilized with medetomidine, zolazepam, and tiletamine (MZT) and collared across west-central Alberta, Canada, 27 of which were individuals being recollared. We examined the distance an individual traveled per day and compared equivalent periods before and after the recollaring event to determine whether postcapture movement rates were significantly different from precapture rates. Within 1 d of the recollaring, daily movement rates had returned to precapture rates (t20=2.09, P=0.18). Our results provide insight on how MZT used in cougars affects their postcapture movement and thus may be helpful in interpreting movement data after release.

Comparison of Butorphanol-Azaperone-Medetomidine and Nalbuphine-Medetomidine-Azaperone in Free-Ranging Elk (Cervus canadensis) in Pennsylvania, USA.

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.

Medetomidine-vatinoxan-midazolam provides similar sedation depth with reduced bradycardia compared to dexmedetomidine-midazolam in pigeons (Columba livia domestica).

OBJECTIVE: To determine if sedation with medetomidine-vatinoxan (Zenalpha; Dechra Veterinary Products) and midazolam (Alvogen) (ZM) would cause less cardiovascular depression and maintain similar depth and duration of sedation in pigeons (Columba livia domestica) compared to dexmedetomidine and midazolam (DM). METHODS: In a blinded crossover study, 15 healthy adult domestic pigeons were sedated IM with either dexmedetomidine (0.08 mg/kg) and midazolam (2 mg/kg) or medetomidine (0.16 mg/kg), vatinoxan (3.2 mg/kg), and midazolam (2 mg/kg) from November through December 2023. Each subject was monitored for 60 minutes, then the sedation was reversed with atipamezole (0.8 mg/kg) and flumazenil (0.1 mg/kg) as needed. Sedation scores, heart rates, and respiratory rates were compared. RESULTS: There was no significant difference in the peak sedation score between DM and ZM groups, with both exhibiting median scores of 4 (heavy sedation). Mean heart rate was significantly higher for ZM than DM at 5, 10, 20, 30, 45, 60, and 65 minutes postinjection. Bradycardia occurred in both groups at 5 and 10 minutes postinjection and persisted for DM until reversal with atipamezole. Arrhythmias were auscultated in both groups. Bradypnea was not observed in either group, and all birds resumed normal behavior following recovery and the following day. CONCLUSIONS: Medetomidine-vatinoxan-midazolam provides a similar depth of sedation to DM but with less incidence of bradycardia. Further study is needed to determine the clinical applicability of this sedative in birds. CLINICAL RELEVANCE: Medetomidine-vatinoxan may be considered for short-term sedation and restraint in cardiovascularly stable pigeons.

Post-surgical photobiomodulation therapy improves outcomes following elective gastropexy in dogs.

PURPOSE: To evaluate the effect of post-surgical photobiomodulation therapy in dogs. METHODS: Twenty dogs were selected for elective gastropexy and randomly divided into a control (CG, n = 10) and a PBMT group (PBMTG, n = 10). Pre­medication consisted of medetomidine and butorphanol. Meloxicam was administered before the procedure. Induction was performed with propofol and maintained with sevoflurane. Local blocks with lidocaine were used. Incisional gastropexy was performed in all animals. PBMTG received PBMT immediately after surgery. The need for postoperative rescue analgesia, if the animal had eaten by the evaluation momen, and pain scores were collected using the Glasgow Composite Measure Pain Scale - Short Form (CMPS­SF) at 1, 2, 4, 6, 8, 12, 16, 20, and 24 h post­endotracheal extubation. CMPS­SF scores were compared with the Mann-Whitney Test and proportions of animals that required rescue analgesia and had eaten with a χ2 test. P was set at < 0.05. RESULTS: No rescue analgesia was needed for any animal. Still, significant differences were observed in CMPS-SF scores between CG and PBMTG between 1 and 4 h post-extubation. PBMTG had a significantly higher proportion of animals eating up to the 8 h post-extubation evaluation moment. CONCLUSION: Adding post-surgical photobiomodulation to a standard anesthesia and analgesia protocol reduced CMPS-SF scores and increased the proportion of animals that resumed eating compared to the standard protocol alone.

Dexmedetomidine directly binds to and inhibits Toll-like receptor 4.

BACKGROUND: While a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult. METHODS: We used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7). RESULTS: We showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC50 = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo. DISCUSSION: We proposed a novel mechanism of dexmedetomidine-mediated neuroprotection.

Use of sedation-awakening electroencephalography in dogs with epilepsy.

BACKGROUND: Electroencephalography (EEG) recording protocols have been standardized for humans. Although the utilization of techniques in veterinary medicine is increasing, a standard protocol has not yet been established. HYPOTHESIS: Assessment of a sedation-awakening EEG protocol in dogs. ANIMALS: Electroencephalography examination was performed in a research colony of 6 nonepileptic dogs (control [C]) and 12 dogs with epilepsy admitted to the clinic because of the epileptic seizures. METHODS: It was a prospective study with retrospective control. Dogs with epilepsy were divided into 2 equal groups, wherein EEG acquisition was performed using a "sedation" protocol (IE-S, n = 6) and a "sedation-awakening" protocol (IE-SA, n = 6). All animals were sedated using medetomidine. In IE-SA group, sedation was reversed 5 minutes after commencing the EEG recording by injecting atipamezole IM. Type of background activity (BGA) and presence of EEG-defined epileptiform discharges (EDs) were evaluated blindly. Statistical significance was set at P > 0.05. RESULTS: Epileptiform discharges were found in 1 of 6 of the dogs in group C, 4 of 6 of the dogs in IE-S group, and 5 of 6 of the dogs in IE-SA group. A significantly greater number of EDs (spikes, P = .0109; polyspikes, P = .0109; sharp waves, P = .01) were detected in Phase 2 in animals subjected to the "sedation-awakening" protocol, whereas there was no statistically significant greater number of discharges in sedated animals. CONCLUSIONS AND CLINICAL IMPORTANCE: A "sedation-awakening" EEG protocol could be of value for ambulatory use if repeated EEG recordings and monitoring of epilepsy in dogs is needed.

Cardiorespiratory effects of intramuscular alfaxalone combined with low-dose medetomidine and butorphanol in dogs anesthetized with sevoflurane.

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/m2 : 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/cm5/m2 : 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.

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl.

BACKGROUND: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. RESULTS: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1-41.6), range (median) versus 0.9 (0-8.0) mL /kg/min] were significantly higher without vatinoxan. CONCLUSIONS: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.

Evaluation of a noncontrolled, pre-euthanasia, intramuscular sedation drug protocol including alfaxalone 4%, medetomidine, and acepromazine for injured or ill raccoons.

Background: As a major animal control service provider in the city of Guelph and Wellington County in Ontario, the Guelph Humane Society transports and presents injured or ill raccoons requiring humane euthanasia to the Ontario Veterinary College Health Sciences Centre (OVC-HSC). Issues around handling, transportation, and delays before euthanasia have recently raised some concerns for welfare and the need for means of improving this process. Objective: Investigation of a noncontrolled sedation and analgesia protocol for injured or ill raccoons intended to improve animal welfare by allowing humane handling, transport, and euthanasia following administration by an animal protection officer (APO). Animals and procedure: Twenty-seven injured or ill raccoons requiring transport and euthanasia, as determined by the Guelph Humane Society APOs, were included in the study. Each raccoon was administered acepromazine (0.05 mg/kg), alfaxalone (4 mg/kg), and medetomidine (0.15 mg/kg), intramuscularly, before being transported to the OVC-HSC for humane euthanasia. Results: The combination of acepromazine, alfaxalone, and medetomidine was suitable for administration by APOs and provided the desired sedation depth to allow transport and humane euthanasia. Transit time was the only predictor of sedation depth upon arrival at the OVC-HSC. Two raccoons showed mild physical response to intracardiac injection for euthanasia. Numerical cutoff points of an in-hospital visual analog score of sedation of ≥ 70/100 and duration of sedation of < 62 min showed zero probability of response to euthanasia. Conclusion and clinical relevance: Administration of acepromazine, alfaxalone, and medetomidine at the stated doses provided acceptable sedation and analgesia to improve animal welfare during transport and eventual euthanasia of raccoons.

Évaluation d'un protocole médicamenteux sans groupe témoin de sédation intramusculaire, pré-euthanasie, comprenant de l'alfaxalone 4 %, de la médétomidine et de l'acépromazine pour les ratons laveurs blessés ou malades. Contexte: En tant que fournisseur majeur de services de contrôle des animaux dans la ville de Guelph et dans le comté de Wellington en Ontario, la Guelph Humane Society transporte et présente les ratons laveurs blessés ou malades nécessitant une euthanasie sans cruauté au Ontario Veterinary College Health Sciences Centre (OVC-HSC). Les problèmes liés à la manutention, au transport et aux délais avant l'euthanasie ont récemment soulevé des inquiétudes quant au bien-être et à la nécessité de trouver des moyens d'améliorer ce processus. Objectif: Enquête sur un protocole de sédation et d'analgésie sans groupe témoin pour les ratons laveurs blessés ou malades destiné à améliorer le bien-être des animaux en permettant une manipulation, un transport et une euthanasie sans cruauté après administration par un agent de protection des animaux (APO). Animaux et procédure: Vingt-sept ratons laveurs blessés ou malades nécessitant un transport et une euthanasie, tel que déterminé par les APO de la Guelph Humane Society, ont été inclus dans l'étude. Chaque raton laveur a reçu de l'acépromazine (0,05 mg/kg), de l'alfaxalone (4 mg/kg) et de la médétomidine (0,15 mg/kg), par voie intramusculaire, avant d'être transporté à l'OVC-HSC pour une euthanasie sans cruauté. Résultats: La combinaison d'acépromazine, d'alfaxalone et de médétomidine convenait à l'administration par un APO et fournissait la profondeur de sédation souhaitée pour permettre le transport et l'euthanasie sans cruauté. Le temps de transit était le seul prédicteur de la profondeur de la sédation à l'arrivée à l'OVC-HSC. Deux ratons laveurs ont montré une légère réponse physique à une injection intracardiaque pour l'euthanasie. Les seuils numériques d'un score analogique visuel de sédation à l'hôpital ≥ 70/100 et d'une durée de sédation < 62 min ont montré une probabilité nulle de réponse à l'euthanasie. Conclusion et pertinence clinique: L'administration d'acépromazine, d'alfaxalone et de médétomidine aux doses indiquées a fourni une sédation et une analgésie acceptables pour améliorer le bien-être des animaux pendant le transport et l'euthanasie éventuelle des ratons laveurs.(Traduit par Dr Serge Messier).

The impact of intravenous medetomidine and vatinoxan on echocardiographic evaluation of dogs with stage B1 mitral valve disease.

INTRODUCTION/OBJECTIVE: The purpose of this study was to investigate the echocardiographic effects of intravenous medetomidine and vatinoxan in dogs with stage B1 mitral valve disease. We hypothesised medetomidine-vatinoxan would reduce the need for manual restraint during echocardiography without producing detrimental cardiovascular effects or echocardiographic changes. ANIMALS: Twelve client-owned dogs with stage B1 mitral valve disease. METHODS: A transthoracic echocardiographic examination was performed before and after sedation with intravenous medetomidine (10 µg/kg) and vatinoxan (200 µg/kg). Vital parameters were also recorded, and the level of sedation was assessed subjectively. The data were analysed with Student's t-tests with an alpha level of <0.05. RESULTS: End-systolic volume and left ventricular systolic diameter increased (from 0.89 ± 0.19 mL/kg to 1.13 ± 0.29 mL/kg and 0.96 ± 0.12 cm to 1.10 ± 0.10 cm, respectively) and ejection fraction (from 66.33 ± 4.0% to 56.23 ± 9.54%) and fractional shortening (from 36.13 ± 5.42% to 27.24 ± 5.6%) decreased significantly after sedation. End diastolic volume, left ventricular diastolic diameter, and left atrial size remained statistically unchanged, while aortic (from 1.34 ± 0.2 m/s to 0.99 ± 0.14 m/s) and pulmonic (from 0.94 ± 0.16 m/s to 0.66 ± 0.15 m/s) velocities decreased significantly. No dogs had a mean arterial pressure below 65 mmHg. Sedation enabled echocardiographic examination without manual restraint. No adverse effects were observed with the dose studied. CONCLUSIONS: Echocardiographic parameters were not completely comparable with the baseline values, which should be taken into consideration when evaluating dogs sedated with intravenous medetomidine-vatinoxan.

How to plan and provide general anesthesia for a troop of 98 hamadryas baboons (Papio hamadryas) for contraceptive and preventative health interventions.

OBJECTIVE: Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates. ANIMALS: 98 hamadryas baboons (Papio hamadryas) held in a German zoological institution. METHODS: A group of 12 veterinarians, 2 zookeepers, and 6 volunteers anesthetized all animals within 2 days. The baboons were orally premedicated with midazolam (0.1 to 0.5 mg/kg) and anesthetized with medetomidine (40 to 60 µg/kg, IM) and ketamine (2 to 4 mg/kg, IM); isoflurane at rates of 1.5% to 2% was used for maintaining anesthesia if necessary. All animals received a physical examination, prophylactic medication, and tuberculin testing. For population management, the animals received a contraceptive implant (adult females), orchiectomy (young males), or vasectomy (breeding males). Young males received intratesticular blocks with lidocaine. All animals received atipamezole (125 to 150 µg/kg) before recovery. RESULTS: Premedication resulted in anxiolysis, which facilitated separating and darting. Median time from darting to access to the animal was 10 minutes. Mean anesthetic times were 25 minutes for females and 55 minutes for males. The depth of anesthesia was appropriate for the procedures. No fatalities were recorded. One animal was injured by other baboons but recovered after treatment. CLINICAL RELEVANCE: Health management and birth control measures are necessary in baboon troops under human care. Anesthesia and/or contraception of individual animals often leads to intraspecific aggression. This case series describes how to provide anesthesia and contraception to an entire troop as an alternative approach that can be adopted to future similar interventions.

Influence of fentanyl, medetomidine-fentanyl or acepromazine-fentanyl premedication on oesophageal and rectal temperature in dogs under anaesthesia.

OBJECTIVE: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl. STUDY DESIGN: Prospective, randomized, blind clinical study. ANIMALS: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg. METHODS: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg-1), MF group with medetomidine (0.005 mg kg-1) and fentanyl (0.01 mg kg-1) and AF group with acepromazine (0.01 mg kg-1) and fentanyl (0.01 mg kg-1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg-1 hour-1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). RESULTS: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.

Auditory brainstem responses are resistant to pharmacological modulation in Sprague Dawley wild-type and Neurexin1α knockout rats.

Sensory processing in the auditory brainstem can be studied with auditory brainstem responses (ABRs) across species. There is, however, a limited understanding of ABRs as tools to assess the effect of pharmacological interventions. Therefore, we set out to understand how pharmacological agents that target key transmitter systems of the auditory brainstem circuitry affect ABRs in rats. Given previous studies, demonstrating that Nrxn1α KO Sprague Dawley rats show substantial auditory processing deficits and altered sensitivity to GABAergic modulators, we used both Nrxn1α KO and wild-type littermates in our study. First, we probed how different commonly used anesthetics (isoflurane, ketamine/xylazine, medetomidine) affect ABRs. In the next step, we assessed the effects of different pharmacological compounds (diazepam, gaboxadol, retigabine, nicotine, baclofen, and bitopertin) either under isoflurane or medetomidine anesthesia. We found that under our experimental conditions, ABRs are largely unaffected by diverse pharmacological modulation. Significant modulation was observed with (i) nicotine, affecting the late ABRs components at 90 dB stimulus intensity under isoflurane anesthesia in both genotypes and (ii) retigabine, showing a slight decrease in late ABRs deflections at 80 dB stimulus intensity, mainly in isoflurane anesthetized Nrxn1α KO rats. Our study suggests that ABRs in anesthetized rats are resistant to a wide range of pharmacological modulators, which has important implications for the applicability of ABRs to study auditory brainstem physiology.

COMPARISON OF THREE MIDAZOLAM-BASED SEDATION PROTOCOLS IN BUDGERIGARS (MELOPSITTACUS UNDULATUS) AND BLACK-CHEEKED LOVEBIRDS (AGAPORNIS NIGRIGENIS).

This randomized, crossover study evaluated three sedation protocols administered subcutaneously in nine budgerigars (Melopsittacus undulatus) and nine black-cheeked lovebirds (Agapornis nigrigenis). All protocols included midazolam (5 mg/kg), combined with butorphanol (5 mg/kg) (BM), medetomidine (20 lg/kg) (MM), or alfaxalone (13 mg/kg) (AM). Mortalities from suspected cardiorespiratory arrest were observed when AM was used in lovebirds, even after reduction of alfaxalone dosage to 3 mg/kg, and therefore this protocol was excluded from further use in this species. Induction and recovery times were recorded and their quality assessed. Sedation depth and heart and respiratory rates were measured every 5 min and radiographic positioning was attempted at 10 and 20 min. At 30 min, midazolam and medetomidine were reversed with flumazenil (0.05 mg/kg, SC), and atipamezole (0.2 mg/kg, SC), respectively. MM consistently provided deep sedation in both species, with successful radiographic positioning at every attempt. As expected, heart rate was often lower with MM than with other protocols, but no associated complications were noted. In budgerigars, BM had the lowest radiographic positioning success rate (10 min: 5/9, 20 min: 3/9), whereas in lovebirds it provided significantly deeper sedation (P < 0.001), allowing radiographic positioning in all subjects. In both species, BM provided the shortest recovery times. AM resulted in reliable radiographic positioning of all budgerigars at 10 min, but not at 20 min (5/ 9), and provided consistently poor recoveries. This study highlights how differently two psittacine species of similar size may react to the same sedation protocols. AM sedation cannot be fully reversed and produced significant undesirable effects, several of which have been previously reported with alfaxalone administration to avian species. The authors therefore caution against using alfaxalone-midazolam combinations in budgerigars and black-cheeked lovebirds. Both BM and MM provided reliable sedation in these species, and appear to be suitable alternatives to AM.

EFFICACY OF TOLAZOLINE AND VATINOXAN IN REDUCING ADVERSE EFFECTS OF BUTORPHANOL-AZAPERONE-MEDETOMIDINE IMMOBILIZATION IN ROCKY MOUNTAIN ELK (CERVUS CANADENSIS).

A mixture of butorphanol, azaperone, and medetomidine (BAM) is frequently used for immobilization of North American hoofstock. Common adverse effects include respiratory depression, hypoxemia, and bradycardia. In this nonblinded crossover study the efficacy of two a-2 adrenergic antagonists, tolazoline and vatinoxan, were evaluated in alleviating adverse effects of BAM in Rocky Mountain elk (Cervus canadensis). Early administration of these antagonists was hypothesized to cause an increase in heart rate, respiratory rate, partial pressure of oxygen (PaO2) and hemoglobin oxygen saturation (SpO2), as well as reduction in mean arterial blood pressure without affecting sedation levels. Eight captive adult female elk were immobilized on three separate occasions at least 14 d apart with 0.15 mg/kg butorphanol, 0.05 mg/kg azaperone, and 0.06 mg/kg medetomidine. Tolazoline (2 mg/kg IM), vatinoxan (3 mg/mg medetomidine IV) or sterile saline (2 ml IM) were administered 20 min postinduction. The BAM caused hypoxemia, bradycardia, and moderate hypertension, and because of the severe hypoxemia observed, all animals received intratracheal oxygen throughout immobilization. Heart rate, respiratory rate, rectal temperature, SpO2, PaO2, and systolic, diastolic, and mean arterial blood pressure were monitored every 5 min throughout the immobilization. Intramuscular tolazoline caused a brief but significant drop in mean arterial pressure compared with controls and a brief but nonsignificant increase in heart rate. Vatinoxan caused a significant drop in blood pressure and a brief significant increase in heart rate. Changes in respiratory rates and PaO2 were not observed with either antagonist; however, all animals received oxygen, which may have influenced this result. The depth of sedation was unchanged after administration of either drug.