Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model.

INTRODUCTION

Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking.

METHODS AND RESULTS

HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 μM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed.

CONCLUSION

In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.