PO-630-08 INFLUENCE OF TWO NARCOSIS REGIMENS ON CARDIAC ELECTROPHYSIOLOGY IN MICE

Abstract

Mouse models are commonly used to study arrhythmia mechanisms in vivo. Different narcosis regimens have proven feasibility in rodents with medetomidine (0.5 mg/kg), midazolam (5 mg/kg) and fentanyl (0.005 mg/kg) (MMF) and isoflurane (1-3 %)/fentanyl (0.05 mg/kg) (IF) among the most commonly used regimens, but little data is available regarding their effects on cardiac electrophysiology. To investigate the effects of MMF and IF narcosis in C57BL/6 wildtype mice on cardiac electrophysiology in vivo. Telemetry transmitters were implanted in 4 C57/BL6 mice which served as controls for ECG analysis without narcosis. In 22 mice ECG and invasive electrophysiology studies were performed under narcosis (n=10 MMF, n=12 IF). We assessed ECG, heart rate variability (HRV), sinus node recovery time (SNRT), atrial, atrioventricular and ventricular refractory periods (AERP, AVERP and VERP), Wenckebach point, VA conduction and arrhythmia inducibility by burst stimulation. MMF causes significant bradycardia (452 bpm baseline vs. 271 bpm MMF, ****p < 0.0001), affects HRV indicated by increased pRR50 (1.6 % baseline vs. 67.4 % MMF, ****p < 0.0001), reduced LF/HF ratio (0.62 baseline vs. 0.16 MMF, *p = 0.019) and both increased SD1 (15 ms baseline vs. 94 ms MMF, ****p < 0.0001) and SD2 (19.6 ms baseline vs. 48.5 ms MMF *p =0.017), and prolongs QRS duration (8.1 ms baseline vs. 11.6 ms MMF, *p = 0.015) and QT interval (50 ms baseline vs. 68 ms MMF, ****p < 0.0001). MMF prolongs SNRT (at 120 ms basic cycle length 234 ms MMF vs. 145 ms IF, ***p < 0.001), antegrade (69 ms MMF vs. 56 ms IF, ****p < 0.0001), and retrograde conduction in the AV node (118 ms MMF vs. 89 ms IF, ***p < 0.001), AVERP (67 ms MMF vs. 50 ms IF, **p < 0.01) and ultimately leads to increased susceptibility for ventricular arrhythmias (1.3 % MMF vs. 0 % IF, **p < 0.01) compared to IF. Our results highlight a significant impact of MMF narcosis on cardiac electrophysiology in mice. While IF only moderately reduces heart rate, MMF leads to significant bradycardia, QRS/QT prolongation and HRV alterations as well as impaired sinus node and AV node function, ultimately resulting in an increased inducibility of ventricular arrhythmias. Based on these effects we suggest using IF narcosis to study cardiac electrophysiology in mice.