Optimization of Xylazine-Ketamine anesthetic dose in mice suffering chronic liver injury

Abstract

Mice and rats are served as the preferable lab animal for biomedical research model due to their small size, ease of handling, short life span and similarity in anatomical, physiological and genetic disceplens to humans. They have been used for in vivo studying of mechanisms of liver fibrosis and its possible treatments. Carbon tetrachloride induced liver fibrosis resembles human liver fibrosis and serves as an attractive model for chronic liver intoxication on the molecular levels.1,2 Completion of certain research may require keeping all participated animals alive, despite of frustrated procedures of examination or samples collection. These procedures are performed in anesthetized mice in order to facilitate the procedure and enable the operator to perform safely and accurately. General anesthesia has been described in lab mice. Ether and isoflurane inhalant agents have been reported for inducing general anesthesia in mice.3 Several injectable protocols have been described. Xylazine 10mg/kg-Ketamine 100mg/ kg, Xylazine 10mg/kg-Ketamine 100mg/kg-Acetyl promazine 3mg/ kg and Diazepam 5mg/kg -Ketamine 200 mg/kg mixtures have been designated for survival procedures in mice.4−7 The combination of ketamine and xylazine is still the most widely used ketamine combination in mice, providing good immobilization with some degree of analgesia. Several different dosage combinations of the ketamine/xylazine mixture have been reported for mice in the medical literature, varying from 65/4 to 100/13 mg/kg. The large variability of the recommended dosages depends on differences related to strain, sex, age, and type of experimental procedure.8−12 Injectable anesthetics may be associated with cardiovascular and respiratory depression, prolonged recoveries, lower margin of safety and hard to control the depth of anesthesia. Both xylazine and ketamine are metabolized by liver enzymes.13 Animals with end stage liver disease are at significant risk of mortality during and after anesthesia and surgery.14 In the text below, we studied four doses of Ketamine-Xylazine mixture, and we report our own experience in selection of a safe and reliable anesthetic protocol.