A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.

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

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

Determination of the effective dosage of tiletamine-zolazepam-ketamine-xylazine, with or without methadone, in dogs.

OBJECTIVE: To determine the effective dosage of the combination tiletamine-zolazepam-ketamine-xylazine (TKX), with or without methadone, in dogs. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A total of 29 dogs. METHODS: Dogs were randomly administered TKX (group TKX, n = 13) or combined with 0.3 mg kg-1 of methadone (group TKXM, n = 16) intramuscularly. The TKX solution contained tiletamine (50 mg mL-1), zolazepam (50 mg mL-1), ketamine (80 mg mL-1) and xylazine (20 mg mL-1). The effective dosages for immobility in 50% and 95% of the population (ED50 and ED95) were estimated using the up-and-down method. Approximately 20 minutes after drug administration, a skin incision was performed and the response was judged as positive or negative if the dogs moved or did not move, respectively. The TKX volume for the subsequent dog in the same group was increased or decreased by 0.005 mL kg-1 if the response of the previous dog was positive or negative, respectively. Heart and respiratory rates, and sedation/anesthesia scores (range 0-21) were recorded before and 15 minutes after drug administration. RESULTS: Estimated ED50 and ED95 (95% confidence intervals) were: TKX, 0.025 (0.020-0.029) and 0.026 (0.010-0.042) mL kg-1; TKXM, 0.022 (0.018-0.025) and 0.033 (0.017-0.049) mL kg-1. Median (interquartile range) scores for sedation/anesthesia were 17 (16-18) and 17 (15-20), and times until lateral recumbency were 5 (4-6) and 6 (4-10) minutes in TKX and TKXM, respectively (p > 0.05). In both groups heart and respiratory rates decreased, but values remained acceptable for anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The results provide a guide for volumes of TKX and TKXM in dogs requiring restraint for minimally invasive procedures. Inclusion of methadone in the TKX combination did not influence ED50.

Rising abuse of veterinary drugs.

ABSTRACT: There has been a significant increase in veterinary drugs found on toxicology screens and postmortem analyses, especially in the Northeast region of the US. This article details the effects and treatment of two common culprits: xylazine and tiletamine-zolazepam.

Evaluation of intramuscular anesthetic protocols in healthy domestic horses.

OBJECTIVE: To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. STUDY DESIGN: Randomized, blinded, three-way crossover prospective design. ANIMALS: A total of eight healthy adult horses weighing 470-575 kg. METHODS: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg-1), ketamine (1 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TKD); ketamine (3 mg kg-1) and detomidine (0.04 mg kg-1) (treatment KD); and tiletamine-zolazepam (2.4 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings-Mack test. A p value <0.05 was considered statistically significant. RESULTS: All horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO2 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: In domestic horses, IM injections of tiletamine-zolazepam-detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine-detomidine and tiletamine-zolazepam-ketamine-detomidine. Recoveries were comparable among protocols.

Physiologic and blood gas effects of xylazine-ketamine versus xylazine-tiletamine-zolazepam immobilization of white-tailed deer before and after oxygen supplementation: a preliminary study.

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 < 0.05. RESULTS: When breathing air, PaO2 was < 80 mmHg (10.7 kPa) in six and seven deer with XK and XTZ, respectively, and of these, PaO2 was < 60 mmHg (8.0 kPa) in three and five deer, respectively. With oxygen supplementation, PaO2 increased to 128 ± 4 and 140 ± 5 mmHg (17.1 ± 0.5 and 18.7 ± 0.7 kPa), mean ± standard error, with XK and XTZ, respectively (p < 0.001). PaO2 was not significantly different between treatments at either time point. HR decreased during oxygen supplementation in both treatments (p < 0.001). Lactate was significantly lower (p = 0.047) with XTZ than with XK (2.2 ± 0.6 versus 3.5 ± 0.6 mmol L-1) and decreased (p < 0.001) with oxygen supplementation (4.1 ± 0.6 versus 1.6 ± 0.6 mmol L-1). PaCO2 increased in XTZ during oxygen breathing. 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.

Comparison of anesthetic effects of tiletamine-zolazepam-medetomidine or ketamine-medetomidine in captive Amur leopard cats (Prionailurus bengalensis euptailurus).

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.

COMPARISON OF TILETAMINE-ZOLAZEPAM COMBINED WITH DEXMEDETOMIDINE OR XYLAZINE FOR CHEMICAL IMMOBILIZATION OF WILD FALLOW DEER (DAMA DAMA).

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.

PHYSIOLOGICAL AND ANESTHETIC EFFECTS OF HAND INJECTION VERSUS DARTING TO INDUCE ANESTHESIA IN CHIMPANZEES (PAN TROGLODYTES).

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 (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO2, oxygen saturation (SpO2), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO2, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia.

Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine-tiletamine-zolazepam anaesthetised red deer (Cervus elaphus).

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 (Pe'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 < 0.05). 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. Pe'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.

EVALUATION OF A PARTIALLY REVERSIBLE IMMOBILIZATION PROTOCOL USING MEDETOMIDINE, BUTORPHANOL, ZOLAZEPAM-TILETAMINE, AND KETAMINE IN FREE-RANGING WARTHOGS (PHACOCHOERUS AFRICANUS) IN KRUGER NATIONAL PARK, SOUTH AFRICA.

Twenty-one free-ranging warthogs (Phacochoerus africanus) in the Kruger National Park, South Africa, were immobilized with a combination of medetomidine (0.07 ± 0.01 mg/kg), butorphanol (0.26 ± 0.04 mg/kg), tiletamine-zolazepam (0.69 ± 0.15 mg/kg), and ketamine (1.43 ± 0.21 mg/kg) administered intramuscularly by dart. Induction, immobilization, and recovery characteristics were evaluated using a standardized scoring system. In the immobilized warthogs, physiological variables were measured every 5 min and arterial blood gases were analyzed at 15-min intervals. At 45 min after initial drug administration, atipamezole (0.34 ± 0.050 mg/kg) and naltrexone (0.53 ± 0.079 mg/kg) were administered intravenously. Overall, induction quality after darting was scored as excellent and the mean time to safe handling was 5.9 ± 2.0 min. Based on muscle relaxation, and loss of palpebral and pedal reflexes, most subjects (17 out of 21) reached a plane of surgical anesthesia by 10 and 15 min; 20 out of 21 warthogs were in this plane for the duration of the monitoring period. In the immobilized warthogs the overall mean heart rate was 65 ± 15.3 beats per minute, mean respiratory rate was 14.7 ± 5.6 breaths per minute, and the mean rectal temperature was 37.9 ± 1.4°C during the 40 min. Arterial blood gas results showed hypoxemia (mean PaO2 62.1 ± 16.2 mmHg), hypercapnia (mean PaCO2 47.1 ± 5.1 mmHg), and acidemia (mean pH = 7.36 ± 0.04). Values for PaO2 and pH improved over the immobilization period. After antagonist administration, overall recovery quality from immobilization was scored as good, with animals standing at a mean time of 7.3 ± 4.9 min. The drug combination proved to be effective in the immobilization of free-ranging warthogs with rapid induction, good anesthesia, and limited cardiorespiratory changes. This anesthetic protocol produces effective, safe, and partially reversible immobilization in warthogs.

FACTORS AFFECTING TEAR PRODUCTION AND INTRAOCULAR PRESSURE IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES).

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or, TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n = 16) than with TZ (11.13 ± 4.63 mm/min; n = 8). Mean IOP, measured using rebound tonometry in an upright body position (n = 8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

Electrocardiographic parameters of Sapajus libidinosus (SPIX, 1823) after chemical immobilization with tiletamine-zolazepam.

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.

Anesthesia effects on the low frequency blood flow oscillations in mouse skin.

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.

Infradian Rhythms of Resistance to a Dissociative Anesthetic in Wistar Male Rats under Normal Conditions and After Surgical Removal of the Adrenal Glands and Testes.

Daily dynamics of changes in the latency of a response to dissociative anesthetic tiletamine (time from injection to ataxia) was studied in mature Wistar rats. Both intramuscular and intravenous administration of the anesthetic was associated with 4-day oscillations of the latent period synchronous with the dynamics of changes in the concentration of glucocorticoid hormones. The period and phases of the infradian rhythm of resistance to the anesthetic remained unchanged after removal of both adrenal glands and testes and administration of corticosterone synthesis blocker trilostane diminishing the 4-day cycle of changes in corticosterone level. Therefore, hormones of the adrenal glands and testes do not play the key role in the mechanisms of formation of the 4-day infradian rhythm.

Identification of Tiletamine, Zolazepam and Their Metabolites in Drug Facilitated Sexual Assault by GC-QTOF-MS.

ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

A clinical study to evaluate the cardiopulmonary characteristics of two different anaesthetic protocols for immobilization of healthy chimpanzees (Pan troglodytes).

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.

Effect of Anesthetics on Efficiency of Remote Ischemic Preconditioning.

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-3ß, 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-3ß. 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.

Development of a sedation protocol using orally administered tiletamine-zolazepam-acepromazine in free-roaming dogs.

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.

Hyaluronidase administered with xylazine-tiletamine-zolazepam into adipose tissue shortens recovery from anesthesia in pigs.

OBJECTIVE: To evaluate the effect of hyaluronidase on uptake, duration and speed of elimination of xylazine-tiletamine-zolazepam administered in the subcutaneous fat over the dorsal lumbar region of swine. STUDY DESIGN: Blinded, randomized, crossover study. ANIMALS: Six healthy Landrace/Large White pigs weighing 132±24 kg (mean±standard deviation). METHODS: Animals were administered xylazine (1 mg kg-1) and tiletamine-zolazepam (8 mg kg-1) (control treatment, CON), or xylazine-tiletamine-zolazepam at the same doses with hyaluronidase (400 IU) (treatment HYA). The treatments were administered into the dorsal lumbar adipose tissue, 2.5-3.0 cm laterally from the spinous process of the second lumbar vertebra. The latency, anesthesia and recovery periods were measured. Heart rate, noninvasive systolic, diastolic, and mean arterial pressures, respiratory rate, hemoglobin oxygen saturation and rectal temperature were recorded every 10 minutes for up to 50 minutes. RESULTS: One animal in CON and one animal in HYA were responsive to stimulation and did not allow safe handling. No significant difference was found between treatments for latency (CON 11.3±5.9 minutes, HYA 7.4±5.1 minutes) and anesthesia (CON 53±53 minutes, HYA 49±38 minutes) periods. Recovery period was shorter in HYA (9±6 minutes) than in CON (32±16 minutes) (p < 0.05). Physiological variables were not significantly changed over time and were within accepted normal clinical limits for the species in both treatments. CONCLUSION AND CLINICAL RELEVANCE: Hyaluronidase (400 IU) administered into adipose tissue in pigs did not reduce the latency and duration of dissociative anesthesia, but was associated with faster recovery.