Cytotoxicity of ketamine, xylazine and Hellabrunn mixture in liver-, heart- and kidney-derived cells from fallow deer.

OBJECTIVES: Chemical restraint of wild animals is practiced to accomplish intended procedures such as capture, clinical examination, collection of diagnostic samples, treatment and/or transport. Extra-label use of animal medicinal drugs is often necessary in wildlife because most approved therapeutics do not list wild species on the labelling. Here, we used cellular in vitro models, a cutting-edge tool of biomedical research, to examine cytotoxicity of anaesthetic agents in fallow deer and extrapolate these data for anaesthetic risks in wildlife. METHODS: We examined the cytotoxic effects of ketamine, xylazine, and ketamine-xylazine, i.e. the Hellabrunn mixture, on liver-, heart- and kidney-derived cell cultures prepared from a fallow deer (Dama dama) specimen. In line with preliminary studies we exposed cells to 10 µM, 50 µM, 100 µM, 1 mM, and 10 mM ketamine or xylazine. The combination of ketamine-xylazine was dosed at 0.025+0.02 mg/ml, 0.05+0.04 mg/ml, 0.75+0.06 mg/ml, 0.1+0.08 mg/ml, and 0.125+0.1 mg/ml per one well containing 10 000 cells. The quantification of cytotoxicity was based on lactate dehydrogenase activity released from damaged cells. RESULTS: Liver-derived cells show higher sensitivity to the cytotoxic effects of both ketamine and xylazine administered as single drugs when compared with cells cultured from the heart and kidney. The Hellabrunn mixture induced significantly higher cytotoxicity for kidney-derived cells ranging from 16.78% to 35.6%. Single and combined exposures to ketamine and xylazine resulted only in high-dose cytotoxicity in the heart-derived cells. CONCLUSIONS: Our results indicate that immobilization drugs significantly differ in their cytotoxic effects on cells derived from various organs of the fallow deer.

The effects of jingsongling, a xylazine analog, on mean arterial blood pressure and heart rate in dogs--influences of yohimbine, tolazoline, prazosin, and atropine.

The effects of jingsongling (JSL) and xylazine on heart rate (HR) and mean arterial pressure (MAP) were studied in five conscious male dogs. An i.v. injection of xylazine (1 mg/kg) caused a bradycardia, an initial hypertension, and a subsequent hypotension. An i.v. injection of JSL (1 mg/kg) caused a bradycardia and a 20-min hypertension without a subsequent hypotension. Atropine sulfate (45 micrograms/kg, i.v.) increased HR for 30 min without changing MAP, and antagonized JSL-induced bradycardia for at least 60 min. There was a subsequent rebound bradycardia. Atropine sulfate potentiated JSL-induced hypertension in both magnitude and duration. Yohimbine (0.1 mg/kg, i.v.), an alpha 2-adrenoceptor antagonist, increased HR and MAP for 110 and 70 min, respectively. Yohimbine not only failed to potentiate but even reversed the pressor effect of JSL in a dose-dependent manner. Yohimbine also caused a dose-dependent reversal of JSL-induced bradycardia. Tolazoline (5 mg/kg, i.v.), a nonselective alpha-adrenoceptor antagonist, increased MAP for 20 min without changing HR. Tolazoline also reversed JSL-induced hypertension and bradycardia. Prazosin (1 mg/kg), an alpha 1-adrenoceptor antagonist, decreased MAP and increased HR for at least 110 min. Prazosin reversed JSL-induced hypertension but failed to affect JSL-induced bradycardia. These results indicated that: (1) JSL-induced bradycardia and hypertension are mediated by alpha 2-adrenoceptors; (2) yohimbine and tolazoline may be useful in antagonizing these untoward reactions associated with JSL administration, whereas prazosin and atropine were not found to be beneficial in this regard.