Optimizing dosage of ketamine and xylazine in murine echocardiography.

1. Ketamine and xylazine (KX) mixture is the most commonly used anaesthetic drug during echocardiography in mice to induce sedation and immobility. Nevertheless, the doses of KX reported in the literature vary substantially with associated significant difference in cardiac function. To explore the optimal KX dosage and observation time for murine echocardiography, we compared the effects of various KX combinations on echocardiographic measurement. 2. Mice were anaesthetized with ketamine (50 or 100 mg/kg) and xylazine (0-10 mg/kg). Echocardiography was performed 5, 10, 20 and 40 min after induction of anaesthesia. Also, cardiac function was assessed in mice with and without pressure-overload induced left ventricle (LV) hypertrophy and dysfunction, either under anaesthesia with KX or whilst conscious. 3. Ketamine at 100 mg/kg alone or together with xylazine at 0.1 mg/kg was associated with a high and stable heart rate (HR), a high fractional shortening (FS) and produced the least effect on LV inner dimension at end of diastole (LVIDd). Ketamine and xylazine at 100 and 10 mg/kg, respectively, produced a lower and stable FS, but with a low and unstable HR. All other combinations resulted in depressed and unstable cardiac function during this period. 4. The dose-dependent suppression of FS by xylazine was counteracted partly by ketamine. 5. Although in the chronic pressure-overload model LV hypertrophy can be detected accurately in both the anaesthetized or conscious state, systolic dysfunction was masked partially by higher doses of xylazine (2.5 or 10 mg/kg) combined with ketamine at 100 mg/kg. 6. With KX anaesthesia, both the dose of xylazine and the anaesthetic duration are critical in achieving an ideal condition for murine echocardiography. Ketamine at 100 mg/kg alone produces acceptable anaesthesia, stable cardiac function with a minimal depressant effect and is therefore recommended if single-dose anaesthetic is to be used.