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Plethysmography is used in nonhuman primates (NHPs) to measure minute volume before aerosol exposure to an agent to calculate total time necessary in the exposure chamber. The consistency of respiratory parameters during the entire exposure time is paramount to ensuring dosing accuracy. Our study sought to validate an alfaxalone-midazolam (AM) anesthetic combination for use in aerosol studies. We hypothesized that AM would provide an adequate duration of anesthesia, achieve and maintain steady state minute volume (SSMV) for 20 min, and have anesthetic quality and side effects comparable to or better than either tiletamine-zolazepam (TZ) and ketamine-acepromazine (KA), the most common anesthetics used for this purpose currently. Two groups of NHPs, one consisting of 15 cynomolgus macaques and one of 15 rhesus macaques, received 3 intramuscular anesthetic combinations (AM, TZ, and KA), no less than one week apart. Anesthetized NHPs were placed in a plethysmograph chamber and their minute volumes were measured every 10 s to determine whether they had achieved SSMV and maintained it for at least 20 consecutive min. Achieving and reliably maintaining an SSMV for at least 20 min facilitates precise aerosol dosing of a challenge agent. Quality of anesthesia, based on the NHP's ability to achieve and maintain SSMV, was higher with AM compared with TZ and KA in both species, and AM had a longer duration of SSMV as compared with TZ and KA in cynomolgus macaques. Average SSMV was larger with AM compared with TZ in cynomolgus macaques, but larger with KA compared with AM in rhesus macaques. Duration of anesthesia was sufficient with all combinations but was longer for TZ than both AM and KA in both species. These results suggest that the AM anesthetic combination would produce the most accurate dosing for an aerosol challenge.

Background Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats. The alpha‐2 agonist, dexmedetomidine, has gained popularity in laboratory animal anesthesia. Tramadol is a weak opioid mu agonist. The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine (ZD) combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol (ZDT) in a minor procedure in rats. Methods Rats were induced with ZD or ZDT. After the loss of paw withdrawal, a small incision was made on the rats’ left thighs as a surgical stimulus. Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes, then atipamezole was administered. Monitored anesthesia parameters included: (a) physiological parameters – pulse rate (PR), respiratory rate (RR), tissue oxygen saturation (%SpO2), and body temperature; (b) duration parameters – induction time, onset and duration of surgical anesthesia plane, onset of recovery, and recovery time. Results PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups. No difference was observed for RR, %SpO2, and body temperature. Likewise, there were no differences for duration parameters: induction time was less than 3 minutes; onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes, respectively; onset of recovery (time to move) was 51 minutes; and recovery time was 52 minutes, respectively. Conclusion These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

A 13-year-old Bornean orangutan diagnosed with life threatening Streptococcus pyogenes broncho-pneumonia was kept in a state of deep sedation for 20 days via continuous intra-venous (IV) infusion of zolazepam -tiletamine and IV haloperidol to allow consistent IV administration of ceftazidime and gatifloxacine. The use of long-term deep sedation allowed carrying out a particularly demanding treatment not generally associated with zoological patients. The treatment was ultimately successful.

This study was aimed to compare the effects of intratesticular (IT) and intramuscular (IM) administration of the zolazepam-tiletamine (ZT) combination on sedation, induction, and recovery qualities and vital variables in cats undergoing castration. Fourteen clinically client-owned healthy cats were randomly assigned to receive 10 mg/kg ZT by either IT or IM routes. Temperament score, injection reaction score, induction time, intubation time, surgical length, anesthesia time, recovery time, and full recovery time were evaluated. Sedation score, heart rate (HR), respiratory frequency (f

Background The potent sedative medetomidine is a commonly used adjunct for the immobilisation of non-domestic mammals. However, its use is associated with pronounced cardiovascular side effects, such as bradycardia, vasoconstriction and decreased cardiac output. We investigated the effects of the peripherally-acting alpha-2-adrenoceptor antagonist vatinoxan on cardiovascular properties in medetomidine-tiletamine-zolazepam anaesthetised wild boar (Sus scrofa). Methods Twelve wild boars, anaesthetised twice with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (2.5 mg/kg) IM in a randomised, crossover study, were administered (0.1 mg/kg) vatinoxan or an equivalent volume of saline IV (control). Cardiovascular variables, including heart rate (HR), mean arterial blood pressure (MAP), pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP) and cardiac output (CO), were assessed 5 min prior to vatinoxan/saline administration until the end of anaesthesia 30 min later. Results MAP (p < 0.0001), MPAP (p < 0.001) and MPAOP (p < 0.0001) significantly decreased from baseline after vatinoxan until the end of anaesthesia. HR increased significantly (p < 0.0001) from baseline after vatinoxan administration. However, the effect on HR subsided 3 min after vatinoxan. All variables remained constant after saline injection. There was no significant effect of vatinoxan or saline on CO. Conclusion Vatinoxan significantly reduced systemic and pulmonary artery hypertension, induced by medetomidine in wild boar.

This article is an attempt to gather available literature regarding the use of tiletamine and zolazepam combination in anaesthesia in dogs and cats. Although tiletamine and zolazepam mixture has been known in veterinary practice for a long time, the increased interest in these drugs has been observed only recently. Tiletamine, similarly to ketamine, is a drug which belongs to the phencyclidine group. Ketamine has considerable popularity in veterinary practice what suggests that other dissociative anaesthetic drugs, such as tiletamine, could also prove effective in cats' and dogs' anaesthetic care. Zolazepam is a widely used benzodiazepine known for its muscle relaxant and anticonvulsant properties. While conducting an electronic search for articles regarding the use of tiletamine-zolazepam combination in dogs and cats, it has been discovered that the literature on the subject (tiletamine-zolazepam combination in dogs and cats) is quite scarce. Very few articles were published after 2010. Databases used were: Google Scholar, Scopus, PubMed. Most of the adverse effects, including those affecting the cardiovascular, nervous, and respiratory systems, were strictly dose-dependent. Tiletamine-zolazepam combination can be safely used as a premedication agent, induction for inhalation anaesthesia, or an independent anaesthetic for short procedures. Contraindications using tiletamine-zolazepam mixture include central nervous system (CNS) diseases such as epilepsy and seizures, head trauma, penetrative eye trauma, cardiovascular abnormalities (hypertrophy cardiomyopathy in cats, arrythmias or conditions where increase of heart rate is inadvisable), hyperthyroidism, pancreatic deficiencies or kidney failure.

Pig experiments often require anaesthesia, and a rapid stress-free induction is desired. Induction drugs may alter the subsequent anaesthesia. Therefore, the aim of the present study was to compare, in pigs, the effects of two different injectable anaesthetic techniques on the induction and on the physiological variables in a subsequent eight hours of total intravenous anaesthesia (TIVA). Twelve domestic castrates (Swedish Landrace/Yorkshire) 27‒31 kg were used. The pigs were randomly assigned to different induction drug combinations of zolazepam–tiletamine and medetomidine intramuscularly (ZTMe) or midazolam, ketamine intramuscularly and fentanyl intravenously (MiKF). Time from injection to unconsciousness was recorded and the ease of endotracheal intubation assessed. The TIVA infusion rate was adjusted according to the response exhibited from the nociceptive stimulus delivered by mechanically clamping the dewclaw. The time from injection to unconsciousness was briefer and intubation was easier in the ZTMe group. Results from the recorded heart rate, cardiac index and arterial blood pressure variables were satisfactorily preserved and cardiovascular function was maintained in both groups. Shivering was not observed in the ZTMe group, but was observed in four of the pigs in the MiKF group. The requirement of TIVA was lower in the ZTMe group. In conclusion, ZTMe had better results than MiKF in areas such as shorter induction time, better intubation scoring results and less adjustment and amount of TIVA required up to six hours of anaesthesia. The results may have been due to a greater depth of anaesthesia achieved with the ZTMe combination at the dose used.

Objective: A large-scale capture method was developed to enable sterilisation of a macropod population in western Sydney from 2005 to 2018. Methods: Until March 2007, free ranging eastern grey kangaroos and red kangaroos were herded into purpose-built 15 m diameter capture yards (CYs) for darting with a projectile syringe. From March 2007 onwards, animals were free-range darted in large areas without herding. Kangaroos were darted with 1.33–5.10 mg/kg tiletamine/zolazepam and 0.01–0.02 mg/kg medetomidine, ± 0.03 mg/kg acepromazine. Deaths were monitored. Population counts were performed annually. Results: There were 5825 capture events involving 3963 kangaroos. Over 85% of all captures occurred from 2005 to 2008. Of all reported deaths (n = 523), 135 were attributed to ill health. Musculoskeletal injuries incurred during capture were the main project-related cause of death (n = 116). Post capture myopathy was uncommonly diagnosed following capture (n = 19). Conclusion: The herding and capture method enabled a large number of kangaroos to be mobilised and captured with low mortality rates, and the use of CYs resulted in fewer capture-related injuries and deaths than free-range capture. The drug doses and combinations used for darting were safe and effective, and the capture technique was successfully applied to a population management project.

OBJECTIVE: To evaluate the tear production, intraocular pressure, and central corneal thickness in healthy white‐tailed deer (Odocoileus virginianus) and assess for seasonal variability. ANIMALS STUDIED: Nineteen healthy fawns (3‐10 days old) and 8 healthy adult white‐tailed deer (164‐280 days old) were studied. PROCEDURES: All fawns were manually restrained for the study, while adult animals were immobilized with an intramuscular injection of combined xylazine (2.2 mg/kg), tiletamine (1 mg/kg), and zolazepam (1 mg/kg). Tear production (STT‐1) was evaluated in both eyes of all fawns. Intraocular pressure (applanation and rebound tonometry) and central corneal thickness (ultrasound pachymetry) were determined in both eyes of all fawns and adult deer. RESULTS: Mean ± SD tear production in fawns was 12.32 ± 4.46 mm/min. Mean ± SD IOP values in the fawns were 16.21 ± 4.97 mm Hg (TonoPen®) and 14.05 ± 5.03 mm Hg (TonoVet®). In adult deer, mean ± SD IOP values were 15.57 ± 2.88 mm Hg with TonoPen® and 12.87 ± 2.57 with TonoVet®, and TonoPen® significantly overestimated the IOP, compared to TonoVet® (P

Background Physiological values reflect the health condition and responses of individuals to handling in captivity. The aim of this study was to establish hematological and serum biochemistry parameters of clinically healthy animals of the Alouatta guariba clamitans subspecies. Methods We collected blood samples from adult males and females kept at the Center for Biological Research of Indaial after chemical containment with 3.9 mg/kg of tiletamine hydrochloride and zolazepam. Results Significant differences between males and females were found in the levels of erythrocytes, hemoglobin, hematocrit, lymphocytes, neutrophils, platelets, mean corpuscular hemoglobin concentration (MCHC), and gamma-glutamyltranspeptidase (GGT). Conclusions Our results suggest the existence of sexual dimorphism in some physiological parameters of A guariba clamitans. The parameters reported herein can be used as reference values for other populations kept under similar conditions.

BACKGROUND Tiletamine-zolazepam is a widely used as an alternative chemical immobilization method in non-human primates, with a safe application pathway and necessary relaxation. In order to determine the electrocardiographic parameters of Sapajus libidinosus after intramuscular tiletamine-zolazepam administration at the dose of 5 mg/kg, nine animals were submitted to anesthesia. METHODS The interpretation of the electrocardiogram determined: heart rate in bpm and heart rhythm, P wave, P-R interval, R wave, QRS complex, T wave, Q-T interval, corrected QT interval and electrical axis. The mean HR was 206 ± 32 bpm. RESULTS The majority of the monkeys showed normal sinus rhythm, but one animal showed sinus tachycardia. The most commonly observed electrical axis was between +30° and +90°. Two animals presented bigger alterations in the tracing such as low amplitude QRS and T wave bigger than 1/4 of the R wave. CONCLUSIONS The administration of tiletamine-zolazepam was safe and efficacious, with minimal cardiovascular effects.

Objectives: The aim of this study was to describe the sedative and some physiological effects of tiletamine?zolazepam following buccal administration (BA) in cats. Methods: Seven healthy spayed European Shorthair cats (three males, four female) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine?zolazepam by BA: the low-dose (LD) consisted of 5 mg/kg of each drug, and the high dose (HD) consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO 2 ) were recorded at predefined intervals for the next 2 h. Results: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for HD than for LD. No values for hemoglobin saturation

OBJECTIVE To compare effects of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for anesthetic induction on cardiorespiratory and acid-base variables before and during isoflurane-maintained anesthesia in healthy dogs. ANIMALS 6 dogs. PROCEDURES Dogs were anesthetized with sevoflurane and instrumented. After dogs recovered from anesthesia, baseline values for cardiorespiratory variables and cardiac output were determined, and arterial and mixed-venous blood samples were obtained. Tiletamine-zolazepam (5 mg/kg), alfaxalone (4 mg/kg), propofol (6 mg/kg), or ketamine-diazepam (7 and 0.3 mg/kg) was administered IV in 25% increments to enable intubation. After induction (M0) and at 10, 20, 40, and 60 minutes of a light anesthetic plane maintained with isoflurane, measurements and sample collections were repeated. Cardiorespiratory and acid-base variables were compared with a repeated-measures ANOVA and post hoc t test and between time points with a pairwise Tukey test. RESULTS Mean ± SD intubation doses were 3.8 ± 0.8 mg/kg for tiletamine-zolazepam, 2.8 ± 0.3 mg/kg for alfaxalone, 6.1 ± 0.9 mg/kg and 0.26 ± 0.04 mg/kg for ketamine-diazepam, and 5.4 ± 1.1 mg/kg for propofol. Anesthetic depth was similar among regimens. At M0, heart rate increased by 94.9%, 74.7%, and 54.3% for tiletamine-zolazepam, ketamine-diazepam, and alfaxalone, respectively. Tiletamine-zolazepam caused higher oxygen delivery than propofol. Postinduction apnea occurred in 3 dogs when receiving alfaxalone. Acid-base variables remained within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs in which a light plane of anesthesia was maintained with isoflurane, cardiovascular and metabolic effects after induction with tiletamine-zolazepam were comparable to those after induction with alfaxalone and ketamine-diazepam.

Effective and adequate anesthesia is conducive to better restrain for pigs during surgical or diagnostic procedures This study aimed to evaluate cardiorespiratory and anesthetic effects of ketamine-midazolam-xylazine-sufentanil or tiletamine-zolazepam-xylazine as general anesthetics in miniature pigs. In phase 1, one of the combinations was administered intramuscularly to miniature pigs. The KMXS protocol combined 10 mg kg-1 ketamine, 0.5 mg kg-1 midazolam, and 2 mg kg-1 xylazine with 2 μg kg-1 sufentanil. The TZX protocol combined 2.2 mg kg-1 tiletamine, 2.2 mg kg-1 zolazepam, and 1.4 mg kg-1 xylazine. After treatment, the mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, and anesthesia quality were recorded. In phase 2, the feasibility of KMXS and TZX as general anesthetics were evaluated for pig castration. In phase 1, both drug combinations provided smooth induction with similar anesthetic effects. The KMXS protocol provided moderate anesthesia for 60–70 minutes in pigs, while the TZX protocol provided 30–45 minutes. In phase 2, castration was completed smoothly in all pigs with little fluctuation in physiological variables. The KMXS protocol is better for medium-term anesthesia, while the TZX protocol is preferable for short-term anesthesia in pigs.

The objective of this study was to evaluate the clinical usefulness of the combination of tiletamine-zolazepam used in low doses as a continuous rate infusion in a partial intravenous anesthesia protocol. Fifteen clinically healthy, different breed bitches weighing 25.08 ± 10.39 kg was used in this study. After a food fast for at least 12 hours and water fast for 4 hours, the animals were premedicated with dexmedetomidine. After 15 minutes, the bolus of tiletamine-zolazepam combination was given as an. Induction of general anesthesia, immediately followed by continuous intravenous infusion. The following parameters were measured immediately after the induction of general anesthesia and lasted until the end of the surgery: electrocardiography, heart rate, systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure, body temperature respiratory rate end tidal of CO

This study compared dexmedetomidine or xylazine in combination with tiletamine-zolazepam for chemical immobilization of wild fallow deer (Dama dama) in a prospective, randomized, blinded clinical study. Forty fallow deer were divided into two groups: tiletamine-zolazepam-xylazine (TZX) and tiletamine-zolazepam-dexmedetomidine (TZD). The TZX group was immobilized with 1.9 ± 0.05 mg/kg of xylazine and 1.48 ± 0.05 mg/kg of tiletamine-zolazepam, whereas the TZD group was immobilized with 34.15 ± 1.1 µg/kg of dexmedetomidine and 0.97 ± 0.03 mg/kg of tiletamine-zolazepam by dart. The induction time was recorded. During the immobilization, heart rate, respiratory rate, body temperature, hemoglobin oxygen saturation, blood lactate concentration, and quality of immobilization were recorded at 10, 20, and 30 m after drug administration. The time of achievement of sternal recumbency and that of standing were also recorded. The TZD group showed a significantly shorter induction time (8 ± 1.6 m, TZX group; 4 ± 0.5 m, TZD group), significantly higher quality of immobilization score (2[1–2], TZX group; 4[4–4], TZD group), and significantly lower lactate levels (5[3–7] mmol/L, TZX group; 2[1–3] mmol/L, TZD group). The time to sternal recumbency was 7 ± 1.6 m (TZX group) and 4 ± 0.5 m (TZD group), and time to quadrupedal standing was 20 ± 1.6 m (TZX group) and 16 ± 0.8 m (TZD group) (P = 0.001). Dexmedetomidine combined with tiletamine-zolazepam is a viable alternative to xylazine for the chemical immobilization of fallow deer.

Temperate zone ungulates like red deer (Cervus elaphus) show pronounced seasonal acclimatisation. Hypometabolism during winter is associated with cardiovascular changes, including a reduction in heart rate (fH) and temporal peripheral vasoconstriction. How anaesthesia with vasoactive substances such as medetomidine affect the seasonally acclimatised cardiovascular system is not yet known. We anaesthetised eleven healthy female red deer with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (3 mg/kg) twice in winter (ad libitum and restricted feed) and in summer (ad libitum and restricted feed), with a two-week washout-period in-between, to test for the effect of season, food availability and supplementation with omega-3 or omega-6 polyunsaturated fatty acid (PUFA) on fH and arterial blood pressure (ABP) during anaesthesia. Six animals received pellets enriched with omega-6 fatty acids (FA), and five animals with omega-3 FA. Anaesthesia significantly decreased fH in summer but not in winter and ABP was lower in winter (p < 0.05). The combination of omega-6 FA enriched pellets and food restriction resulted in a lower fH and higher ABP during anaesthesia with more pronounced changes in winter (p < 0.001). Our results demonstrate that season, food availability and type of PUFA supplementation in red deer affect the cardiovascular system during anaesthesia.

OBJECTIVE To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a reversal agent. ANIMALS 11 healthy 2.5-month-old castrated male Landrace mixed-breed pigs. PROCEDURES In a randomized, blinded crossover study design, pigs received the following anesthetic combinations, IM: TZDB (tiletamine-zolazepam [3 mg/kg {1.36 mg/lb}], detomidine [0.18 mg/kg {0.08 mg/lb}], and butorphanol [0.12 mg/kg {0.05 mg/lb}]); TZXB (tiletamine-zolazepam [4 mg/kg {1.8 mg/lb}], xylazine [4 mg/kg], and butorphanol [0.2 mg/kg {0.09 mg/lb}]); and KDB (ketamine [8 mg/kg {3.63 mg/lb}], detomidine [0.18 mg/kg], and butorphanol [0.3 mg/kg {0.14 mg/lb}]). A 7-day washout period was provided between treatments. At 45 minutes of anesthesia, pigs received tolazoline (2 mg/kg [0.9 mg/lb], IM; n = 6) treatment or control (5) treatment with saline (0.9% NaCl) solution. RESULTS All anesthetic combinations induced anesthesia. Endotracheal intubation was completed within 5 minutes after anesthetic administration in all pigs, except in 2 pigs following administration of KDB. Durations (mean ± SD) of endotracheal intubation and lateral recumbency in pigs that did not receive tolazoline were 55.3 ± 4.8 minutes, 83.8 ± 15.8 minutes, and 28.2 ± 4.5 minutes and 112.4 ± 18.7 minutes, 117.2 ± 16.7 minutes, and 79.7 ± 6.0 minutes, respectively, for the TZDB, TZXB, and KDB anesthetic treatments. Tolazoline significantly shortened the duration of anesthetic recovery for all anesthetic treatments without affecting the recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE All 3 anesthetic combinations were suitable for providing anesthesia in pigs. Tolazoline administration shortened the duration of anesthetic recovery without affecting the quality of recovery.

Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (

Wild animal immobilization often requires high doses of α2-adrenoceptor agonists. Despite their desired sedative and analgetic effects, well-recognized cardiovascular side effects, such as hypertension and bradycardia, remain a major concern. We compared the effect of two medetomidine doses on intra-arterial blood pressure and heart rate in 13 captive, female red deer (Cervus elaphus) immobilized during winter. Each animal was randomly assigned to receive either 80 µg/kg (group L) or 100 µg/kg (group H) medetomidine, combined with 3 mg/kg tiletamine-zolazepam administered intramuscularly. Changes in cardiovascular variables over time and differences between the groups were analyzed using linear mixed-effect models. Induction time was faster in group L compared with group H; recovery time did not differ between groups. Initially, the arterial blood pressure was higher in group H compared with group L, but differences between groups diminished during anesthesia. Moreover, the decline in arterial blood pressure in group H was more rapid. Heart rate was significantly lower in group L, but bradycardia was not observed. The higher medetomidine dose did not reduce induction time, and initial hypertension was reduced by administering the lower dose. Therefore, although the sample size was small and, thus, the significance of results might be limited, we suggest using 80 µg/kg instead of 100 µg/kg medetomidine when combined with 3 mg/kg tiletamine-zolazepam for the immobilization of female red deer.

Neural oscillations of the mammalian olfactory system have been studied for decades. This research suggests they are linked to various processes involved in odor information analysis, depending on the vigilance state and presentation of stimuli. In addition, the effects of various anesthetics, including commonly used ones like chloral hydrate, pentobarbital, ketamine, and urethane, on the local field potential (LFP) in the olfactory bulb (OB) have been studied. In particular, the combination of xylazine and tiletamine–zolazepam has been shown to produce steady anesthesia for an extended period and relatively few adverse effects; however, their effects on the LFP in the OB remain unknown. To study those effects, we recorded the LFP in the OB of rats under xylazine–tiletamine–zolazepam anesthesia. During the period of anesthesia, the spectral powers of the 1–4, 9–16, 31–64, 65–90 frequency bands increased significantly, and that of 91–170 Hz frequency band decreased significantly, whereas no significant changes were observed in the 5–8 and 17–30 Hz ranges. These results reveal dynamic changes in the time and frequency characteristics of the LFP in the OB of rats under xylazine–tiletamine– zolazepam anesthesia and suggest that this combination of anesthetics could be used for studying oscillatory processes in the OB of rats.

Objective To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine–tiletamine–zolazepam in red deer (Cervus elaphus). Study design and animals A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study. Methods Deer were administered a combination of 0.1 mg kg–1 medetomidine hydrochloride and 2.5 mg kg–1 tiletamine–zolazepam intramuscularly, followed by 0.1 mg kg–1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (P e ′CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p Results Maximal (81 ± 10 beats minute–1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute–1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute–1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. P e ′CO2, fR and SpO2 showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan. Conclusions and clinical relevance Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine–tiletamine–zolazepam.

Objective To evaluate the effects and utility of tiletamine–zolazepam–medetomidine (TZM) and ketamine–medetomidine (KM) for anesthesia of Amur leopard cats (Prionailurus bengalensis euptailurus). Study design Prospective, randomized experimental trial. Animals A total of six female (3.70 ± 0.49 kg) and six male (5.03 ± 0.44 kg; mean ± standard deviation) Amur leopard cats aged 2–6 years. Methods Each animal was administered four protocols separated by ≥3 weeks. Each protocol included medetomidine (0.05 mg kg–1) combined with tiletamine–zolazepam (1 mg kg–1; protocol MTZLO); tiletamine–zolazepam (2 mg kg–1; protocol MTZHI); ketamine (2 mg kg–1; protocol MKLO); or ketamine (4 mg kg–1; MKHI) administered intramuscularly. At time 0 (onset of lateral recumbency) and 30 minutes, heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and hemoglobin oxygen saturation (SpO2) were recorded. Times to onset of lateral recumbency, duration of anesthesia and time to standing were recorded. Results Overall, animals were anesthetized with all protocols within 10 minutes, anesthesia was maintained ≥57 minutes, and recovery (time from the first head lift to standing) was completed within 5 minutes. During anesthesia with all protocols, HR, fR, rectal temperature, SpO2 and MAP were 99–125 beats minute–1, 33–44 breaths minute–1, 37.6–39.4 °C, 90–95% and 152–177 mmHg, respectively. No adverse event was observed. Conclusions and clinical relevance TZM and KM at various dosages resulted in rapid onset of anesthesia, duration of >57 minutes and rapid recovery without administration of an antagonist. Accordingly, all these combinations are useful for anesthetizing Amur leopard cats and for performing simple procedures. However, the low doses of the anesthetic agents are recommended because there was no difference in duration of anesthesia between the dose rates studied.

Thoracotomy is an uncommon procedure in horses but remains essential in a variety of cases of pleuropneumonia, pericarditis, thoracic trauma or diaphragmatic herniation, and for experimental thoracic and cardiac procedures. This study aimed at developing an experimental surgical procedure allowing access to the entire circumference of the heart and describing the effect of thoracotomy on pulmonary gas exchange in these horses. The study consisted of two arms, arm one (undergoing thoracotomy), was a terminal experimental study that included 11 Standardbred horses with experimentally induced (by tachypacing) atrial fibrillation. Arm two consisted of 6 Standardbred horses undergoing anesthesia for reasons unrelated to the present study. These horses functioned as controls. Anesthesia was induced using zolazepam and tiletamine. Anesthesia was maintained with isoflurane in 100% oxygen and ventilation with intermittent positive pressure (IPPV); no positive end-expiratory pressure (PEEP) was performed. Rib resection and pericardiotomy were performed for complete exposure of the entire circumference of the heart. Arterial blood samples were collected prior to, 5 and 30 minutes after puncture of pleura parietalis. In 10 horses, resection of the fifth rib was adequate for exposure of the heart. In one horse, removal of the sixth rib was also necessary. The duration of the surgical procedure (thoracotomy, pericardiotomy) was45 minutes. During a thoracotomy, PaO

Background Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. Methods Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. Results Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. Conclusions Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (

Background When laboratory animals are used one needs to anesthetize them before recording. However, the influence of anesthesia on animal blood flow oscillations has not been studied. The effects of two ways of anesthesia, zoletil-xylazine, and zoletil-nitrous oxide mixtures, on mouse skin perfusion using laser Doppler flowmetry (LDF) technique were studied. Methods BALB/c mice were used. LDF probe was placed on the ventral surface of the left hind paw. Spectral analysis of LDF signals was performed with continuous adaptive wavelet transform to identify and describe peripheral blood flow oscillations in mouse skin. Results Low-frequency oscillation interval boundaries (myogenic, neurogenic, and endothelial) for mice were shown to coincide with the boundaries determined for human and rats, that demonstrate their independence from the body size. Zoletil-xylazine anesthesia significantly decreased neurogenic and endothelial oscillation amplitudes by 29% and 50% respectively and increased the amplitude of cardiac oscillations by 23% compared to zoletyl-nitrous oxide anesthesia. There were no significant changes of the amplitudes of myogenic and respiratory oscillations with zoletil-nitrous oxide anesthesia compared to the zoletil-xylazine mixture. Conclusion We suggest that the different influence of anesthesia modes on the amplitudes of skin blood flow oscillations is associated with sympathetic activity suppressed by zoletil-xylazine anesthesia.

OBJECTIVE To develop a technique for permanent sterilisation of female eastern grey kangaroos (Macropus giganteus) and red kangaroos (M. rufus) as part of a large-scale macropod management program on an enclosed 1545-ha site in western Sydney. METHODS Free-ranging female kangaroos (n = 1409: 1285 eastern grey kangaroos, 124 red kangaroos) were anaesthetised via remote anaesthetic drug delivery of tiletamine/zolazepam, medetomidine and acepromazine prior to inhalational anaesthesia using isoflurane-oxygen. A laparoscopic ovariectomy technique was developed using standard laparoscopic equipment to effect permanent sterilisation of the kangaroos. The technique described was also adapted for use on immature animals weighing as little as 1 kg. No direct post-surgical care was provided once the animals had recovered from the anaesthetic. RESULTS The procedure was simple to perform and had a very high success rate, with an overall project mortality rate of 2.13% (n = 30). Seven kangaroos (0.05% of all operated kangaroos) were euthanased as a direct result of the surgical procedure. Surgical complications were rare but included inadvertent gastrointestinal tract puncture with the trocar, intraoperative haemorrhage and subcutaneous emphysema leading to pouch eversion following surgery. CONCLUSION The procedure described is a rapid and effective method of permanent fertility control in macropods and carries a low mortality rate.

Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3β, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3β. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection.

Objective To investigate the sedative effects in dogs of tiletamine–zolazepam–acepromazine (TZA) or ketamine–flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs. Study design Experimental study followed by a field trial. Animals Six research dogs and 27 free-roaming dogs. Methods In a pilot study, six research dogs were administered liquid TZA (20 mg kg−1 tiletamine–zolazepam and 2 mg kg−1 acepromazine) or liquid KF (50 mg kg−1 ketamine and 2 mg kg−1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs. Results In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35–80) minutes (67%); treatment 2, 30 (15–65) minutes (83%); and treatment 3, 75 (45–110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg−1) and acepromazine (2 mg kg−1). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg−1) and xylazine (1.1–2.2 mg kg−1) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food. Conclusions and clinical relevance Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate.

Anesthetics utilized for the immobilization of pregnant mammals are prone to crossing the placental barrier and cause adverse effects to the fetuses. In this study, we develop a facile method employing high performance liquid chromatography (HPLC) for the study of Telazol crossing the placental barrier of pregnant pigs. The method mainly relies on the efficient extraction strategy that includes the mobile phase composed of 10 mM ammonium acetate aqueous solution-acetonitrile (1:4, v/v). When the injected dose of Telazol is 10 mg/kg (5 mg/kg of each constituent drug, zolazepem and tiletamine), zolazepam can cross the placental barrier as it is detected in both uterus and umbilical cord with approximately the same content. Conversely, tiletamine is detected in neither uterus nor umbilical cord, indicating the absence of placental transfer of tiletamine. The different absorption rates of the two dosage-equal compounds by pigs are found to be the main cause of their different abilities to cross the placental barrier.

The objective of this study was to determine the dose-dependent effects of isoflurane on various cardiovascular parameters and the stable range of isoflurane concentrations in Asiatic black bears (Ursus thibetanus). Seven Asiatic black bears were intramuscularly injected with medetomidine, zolazepam and tiletamine (MZT) to induce anesthesia, and anesthesia was maintained by administering isoflurane in 100% oxygen (4 l/min) without mechanical ventilation. Several cardiovascular parameters were measured at five end-tidal isoflurane concentrations (0.5, 1.0, 1.5, 2.0, and 2.5%). Blood was collected from the femoral artery before administration of isoflurane and after each administration for immediate blood gas analysis. Isoflurane produced dose-dependent increases in heart rate, respiratory rate, minute volume, end-tidal carbon dioxide (CO2) partial pressure and the partial pressure of arterial CO2, and dose-dependent decreases in non-invasive blood pressure and tidal volume. Rectal temperature, oxygenation and acid-base balance were unaffected by isoflurane. All parameters in this study were in a clinically acceptable range at all times. The data show that the combination of MZT and isoflurane is suitable for general anesthesia in Asiatic black bears with spontaneous breathing during prolonged procedures. End-tidal isoflurane concentrations of 0.5 to 2.5% can be used in Asiatic black bears without adverse side effects.

Twenty-one free-ranging warthogs (

Objective To compare oxygenation and ventilation in white-tailed deer (Odocoileus virginianus) anesthetized with two treatments with and without oxygen supplementation. Study design Randomized, blinded, crossover study. Animals A total of eight healthy adult white-tailed deer weighing 49–62 kg. Methods Each deer was anesthetized twice intramuscularly: 1) treatment XK, xylazine (2 mg kg–1) and ketamine (6 mg kg–1) and 2) treatment XTZ, xylazine (2 mg kg–1) and tiletamine–zolazepam (4 mg kg–1). With the deer in sternal position, arterial and venous blood was collected before and at 30 minutes during administration of oxygen at 1 L minute–1 through a face mask. PaO2 and heart rate (HR) were compared using two-way repeated measures anova . pH, PaCO2 and lactate concentration were analyzed using mixed-effects linear models, p Results When breathing air, PaO2 was Conclusions and clinical relevance Treatments XK and XTZ resulted in hypoxemia, which responded to oxygen supplementation. Both treatments are suitable for immobilization of white-tailed deer under the study circumstances.

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol. DESIGN Prospective, randomized crossover study. ANIMALS 6 healthy adult hounds. PROCEDURES Each dog underwent the 4 treatments in random order with a ≥ 7-day washout period between anesthetic episodes. Anesthesia was induced by IV administration of the assigned induction drug or combination (each to effect in 25% increments of calculated dose) and maintained with isoflurane in oxygen for 60 minutes. Cardiorespiratory variables and end-tidal isoflurane concentration (ETISO) were measured just before isoflurane administration was discontinued. Dogs were observed and video recorded during recovery. Recovery characteristics were retrospectively scored from recordings by 3 raters. Interrater and intrarater reliability of scoring was assessed by intraclass correlation coefficient calculation. Linear and mixed ANOVAs were used to compare extubation times, recovery scores, and body temperature among treatments. RESULTS Most cardiorespiratory variables, body temperature, ETISO, and time to extubation did not differ between tiletamine-zolazepam and other induction treatments. Recovery scores were lower (indicating better recovery characteristics) with propofol or alfaxalone than with tiletamine-zolazepam but did not differ between tiletamine-zolazepam and ketamine-diazepam treatments. Anesthetic episode number and ETISO had no effect on extubation time or recovery score. Intrarater and interrater correlations for recovery scores were excellent. CONCLUSIONS AND CLINICAL RELEVANCE Recovery of healthy dogs from anesthesia with isoflurane after induction with tiletamine-zolazepam was uncomplicated and had characteristics comparable to those observed following induction with ketamine-diazepam. However, recovery characteristics were improved when anesthesia was induced with propofol or alfaxalone.

Objectives The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol. Methods All healthy cats presenting solely for gonadectomy to two trap–neuter–return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points). Results Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86–6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01–6.43). The difference between mean scores was 0.17 (–0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints. Conclusions and relevance The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.

OBJECTIVE To evaluate the effect of IM administration of a tiletamine hydrochloride–zolazepam hydrochloride (TZ) combination with either dexmedetomidine hydrochloride or saline (0.9% NaCl) solution (SS) on the motor response to claw clamping, selected cardiorespiratory variables, and quality of recovery from anesthesia in alpacas. ANIMALS 5 adult sexually intact male alpacas. PROCEDURES Each alpaca was given the TZ combination (2 mg/kg) with dexmedetomidine (5 [D5], 10 [D10], 15 [D15], or 20 [D20] µg/kg) or SS IM at 1-week intervals (5 experiments); motor response to claw clamping was assessed, and characteristics of anesthesia, recovery from anesthesia, and selected cardiorespiratory variables were recorded. RESULTS Mean ± SEM duration of lack of motor response to claw clamping was longest when alpacas received treatments D15 (30.9 ± 5.9 minutes) and D20 (40.8 ± 5.9 minutes). Duration of lateral recumbency was significantly longer with dexmedetomidine administration. The longest time (81.3 ± 10.4 minutes) to standing was observed when alpacas received treatment D20. Following treatment SS, 4 alpacas moved in response to claw clamping at the 5-minute time point. Heart rate decreased from pretreatment values in all alpacas when dexmedetomidine was administered. Treatments D10, D15, and D20 decreased Pao2, compared with treatment SS, during the first 15 minutes. During recovery, muscle stiffness and multiple efforts to regain a sternal position were observed in 3 SS-treated and 1 D5-treated alpacas; all other recoveries were graded as excellent. CONCLUSIONS AND CLINICAL RELEVANCE In TZ-anesthetized alpacas, dexmedetomidine (10, 15, and 20 µg/kg) administered IM increased the duration of lack of motor response to claw clamping, compared with the effect of SS.

Forty rescued common palm civets were anesthetized. Twenty animals received intramuscular injections of alfaxalone 5 mg/kg and medetomidine 0.05 mg/kg (A-M group), whereas twenty animals received 5 mg/kg of tiletamine and zolazepam (T-Z group). The A-M group was reversed with atipamazole 0.25 mg/kg. There were no significant differences in the time from anesthetic injection to induction and intubation between the A-M and T-Z groups. The time from the injection of reversal in the A-M group and the time from cessation of isoflurane in the T-Z group to extubation, first response to recovery and ambulation were longer (P

The aim of study was to review the status of arterial pH, pO2 and pCO2 under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO2, and pCO2 were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO2 only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

Health evaluations were conducted on individuals ( n = 62, age1 to 11 yr) from a captive red panda ( Ailurus fulgens styani) population at the Chengdu Research Base for Giant Panda Breeding in Sichuan Province, People's Republic of China. Individuals were anesthetized using combinations of ketamine, dexmedetomidine, diazepam, isoflurane, and tiletamine/zolazepam. Whereas physical exams revealed no abnormalities for 40% of red pandas, 24% had dental abnormalities and 18% had orthopedic abnormalities. As the red panda is the only member of the family Ailuridae, complete blood count and serum biochemistry samples were collected and used to develop reference intervals for this species. When hematologic and serum chemistry values of male and female red pandas were compared within this A. f. styani population, males had higher mean cell hemoglobin, mean cell hemoglobin concentration, and blood urea nitrogen concentrations, whereas females had higher alkaline phosphatase, cholesterol, and iron. Adult red pandas (≥2 yr) had higher lymphocyte percentage, total protein, globulin, and chloride levels, whereas juveniles (2 yr) had higher white blood cell concentrations, neutrophil percentage and absolute neutrophil values, alkaline phosphatase, creatine kinase, cholesterol, potassium, total and ionized calcium, and phosphorus levels. Reference values and expected age and sex differences will assist with health management of the captive A. f. styani population.

Laboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of p = 0.783). However, the withdrawal reflex was lost in all snakes receiving 3mg/kg of tiletamine+zolazepam but not in all animals of the other two groups (p = 0.0004). In addition, the time for animals to regain the righting reflex and resume normal behavior was longer in the drug combination dose groups compared to the midazolam group (p = 0.0055). Our results indicate that midazolam is an adequate sedative for ball pythons but does not suffice to achieve reliable immobilization or anesthesia, whereas tiletamine+zolazepam achieves short-term anesthesia in a dose-dependent manner.

Zoletil is an anesthetic and immobilizing drug that has been used in the veterinary field for over 50 years; however, the effect of Zoletil, or its constituents, on brain cystathionine β-synthase (CBS) remains unknown. Here, we aimed to determine the effect of Zoletil on rat brain CBS by administering a single intraperitoneal injection of the drug and examining hydrogen sulfide (H2S) and CBS levels in the cerebral cortex, hippocampus, and thalamus following three distinct behavioral phenotypes associated with the sedation procedure (e.g., loss of the righting reflex, return of the righting reflex, and return of walking). Zoletil administration resulted in significant decreases of endogenous H2S in the cerebral cortex, hippocampus, and thalamus, and H2S was observed to increase in these brain regions when rats recovered from the anesthesia. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry revealed that CBS expression in the cerebral cortex and hippocampus exhibited the same trend as endogenous H2S following Zoletil administration. In summary, our results demonstrated that Zoletil induced the expression of CBS which could exert region-specific regulation of H2S in the cerebral cortex and hippocampus.

Objective To characterize the cardiopulmonary characteristics of two different anaesthetic protocols (tiletamine/zolazepam ± medetomidine) and their suitability for the immobilization of healthy chimpanzees undergoing cardiac assessment. Study design Prospective, clinical, longitudinal study. Animals Six chimpanzees (Pan troglodytes) aged 4–16 years weighing 19.5–78.5 kg were anaesthetized on two occasions. Methods Anaesthesia was induced with tiletamine/zolazepam (TZ) (3–4 mg kg–1) or tiletamine/zolazepam (2 mg kg–1) and medetomidine (0.02 mg kg–1) (TZM) via blow dart [intramuscular (IM)] and maintained with intermittent boluses of ketamine (IV) or zolazepam/tiletamine (IM) as required. The overall quality of the anaesthesia was quantified based on scores given for: quality of induction, degree of muscle relaxation and ease of intubation. The time to achieve a light plane of anaesthesia, number of supplemental boluses needed and recovery characteristics were also recorded. Chimpanzees were continuously monitored and heart rate (HR), pulse rate (PR), respiratory rate (fR) oxygen saturation of haemoglobin (SpO2), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal temperature, mucous membrane colour and capillary refill time recorded. During the first procedure (TZ) animals underwent a 12-channel electrocardiogram (ECG), haematology, biochemistry and cardiac biomarker assessment to rule out the presence of pre-existing cardiovascular disease. A detailed echocardiographic examination was carried out by the same blinded observer during both procedures. Data were compared using Student’s paired t-test or Wilcoxon rank tests as appropriate. Results There was a significant difference for the area under the curves between anaesthetic protocols for HR, SAP, MAP and fR. No significant differences in the echocardiographic measurements were evident. Quality of anaesthesia was significantly better with TZM and no additional boluses were required. The TZ protocol required multiple supplemental boluses. Conclusions and clinical relevance Both combinations are suitable for immobilization and cardiovascular evaluation of healthy chimpanzees. Further work is required to evaluate the effect of medetomidine in cardiovascular disease.

Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12 %, and the recoveries of the analytes exceeded 70 % in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01 % for zolazepam and 2.09 ± 0.51 % for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories.

Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil. Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil. Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil. Universidade do Estado do Par?. Centro de Ci?ncias Biol?gicas e da Sa?de. Laborat?rio de Cirurgia Experimental. Bel?m, PA,Brazil. Universidade Federal Rural da Amaz?nia. Instituto da Sa?de e Produ??o Animal. Bel?m, PA, Brazil. Background Feline night monkeys are very susceptible to stress when handled, and because of that, the use of anesthetic and physical restraint methods should be carefully evaluated. To ensure a safer anesthesia to the animals the present study aimed to observe the influence of four restraint protocols in the blood pressure of Aotus azarae infulatus. Methods Blood pressure was obtained from 10 animals subjected to restraining protocols using tiletamine and zolazepam, isoflurane, ketamine and midazolam, and physical restraint and results were evaluated to determine their effect on this exam. Results Among the restraint protocols tested, the anesthetic isoflurane promoted lower blood pressure values and no differences were observed between values measured in both arms in all groups. Conclusion The results of our study suggest that all restraint protocols tested significantly alter blood pressure in this species of primates.

We used a combination of medetomidine and tiletamine-zolazepam to immobilize five Himalayan black bears (Selenarctos thibetanus laniger) in Bannerghatta Biological Park, Bangalore, India. Medetomidine and tiletamine-zolazepam were administered at 0.01 mg/kg and 0.5 mg/kg, respectively. We describe procedures and observations recorded during the immobilization.

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.

Pigs are commonly used in diabetes research due to their many physiological similarities to humans. They are especially useful in imaging procedures because of their large size. However, to achieve imaging procedures the pig must lie completely still, and thus needs to be anaesthetized. Most anaesthetic drugs used in laboratory animals affect carbohydrate metabolism by the inhibition of insulin release. The aim of this pilot study was primarily to develop an anaesthetic protocol for pigs that did not have an effect on blood glucose levels throughout the 3 h of anaesthesia; and secondly, to evaluate the most promising protocol in combination with an oral glucose tolerance test (OGTT). Two anaesthetic protocols were used in four growing pigs. Intravenous propofol infusion caused hyperglycaemia in three out of four pigs within 5–10 min after induction and was therefore excluded. Intravenous infusion with tiletamine, zolazepam and butorphanol (TZB) for 3 h did not affect blood glucose levels. The pigs underwent OGTT twice, once without anaesthesia and once with TZB induction after glucose intake. Anaesthesia during OGTT resulted in a lower area under the curve (AUC) of glucose ( P