Medetomidine/vatinoxan (Zenalpha®) is a novel anesthetic combination used as a sedative and analgesic in dogs. Vatinoxan minimizes adverse cardiopulmonary effects associated with medetomidine administration while preserving sedation and analgesia. In this study, we evaluated the clinical safety and efficacy of 3 dosage combinations of Zenalpha with ketamine and buprenorphine extended release (ER) as compared with xylazine with ketamine and buprenorphine-ER for anesthesia of C57BL/6J mice. We hypothesized that anesthesia with 0.5 mg/kg of Zenalpha would more reliably provide a surgical anesthetic plane, lower mortality, and fewer adverse physiologic effects as compared with anesthesia with 8 mg/kg of xylazine. Ten-week-old male and female C57BL/6J mice were randomly administered 1 of 4 anesthetic cocktails subcutaneously: ketamine (80 mg/kg) and buprenorphine-ER (0.5 mg/kg) with 1) xylazine (8 mg/kg; XKB); 2) Zenalpha (0.25 mg/kg; ZKB/0.25); 3) Zenalpha (0.5 mg/kg; ZKB/0.5); or 4) Zenalpha (1.0 mg/kg; ZKB/1.0). Following drug administration, we assessed the anesthesia induction time by measuring the time to loss of righting reflex and loss of paw withdrawal reflex (PWR). Upon reaching a loss of righting reflex, physiologic parameters including heart rate, respiratory rate, oxygen saturation, indirect mean arterial blood pressure, body temperature, jaw tone, and skin color were monitored every 5 min. Thirty minutes after anesthetic drug administration (TA), atipamezole (1 mg/kg SC) was administered. Recovery time was determined through time until return of PWR, righting reflex, and ambulation. Mice were monitored for 3 d postanesthesia. Results included: 1) ZKB anesthesia caused loss of PWR in a dose-dependent manner; 2) physiologic parameters were similar between XKB and ZKB mice by TA in 100% O2; 3) ZKB groups took longer to recover and had a 20% to 30% mortality rate in the mid-to-high dosage groups. We conclude that anesthesia with 0.5 mg/kg of Zenalpha more reliably produced a surgical anesthetic plane but also led to decreased mean arterial pressure and increased mortality as compared with anesthesia with 8 mg/kg of xylazine. We recommend using Zenalpha (0.25 to 1.0 mg/kg) with 80 mg/kg ketamine and 0.5 mg/kg buprenorphine-ER to provide general anesthesia in C57BL/6 mice, along with supplemental 100% oxygen and atipamezole.
Experimental timeline of anesthesia, from treatment administration (TX) to recovery (TA).
Heart rate was measured in beats per minute (mean ± SE). *, P < 0.05 when ZKB groups were compared with XKB at each time point. There were significant differences in HR between XKB and ZKB groups at baseline T0 but became insignificant at 5 min and onwards.
Mean arterial pressure was measured in millimeters of mercury (mean ± SEM). *, P < 0.05 when ZKB groups were compared with XKB at each time point. From T5 to T30, MAP was significantly higher in XKB mice compared with ZKB mice.
Respiratory rate was measured in breaths per minute (mean ± SEM). *, P < 0.05 when ZKB groups were compared with XKB at each time point. Significant differences in RR between XKB and ZKB mice occurred during the first 25 min of anesthesia.
Histologic findings included cardiomyocyte vacuolation within (A) left ventricle and (B) microvesicular hepatic vacuolation. Hematoxylin and eosin, 40× magnification. Scale bar = 20 µm.
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