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

J Cardiovasc Electrophysiol. 2014 Apr;25(4):431-439. doi: 10.1111/jce.12320. Epub 2013 Dec 9.


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.

Keywords: calcium; dantrolene; heart failure; myocardial infarction; optical mapping; pharmacology; ventricular fibrillation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Cardiac Complexes, Premature / complications
  • Cardiac Complexes, Premature / drug therapy*
  • Cardiac Pacing, Artificial
  • Coronary Vessels / physiology
  • Dantrolene / therapeutic use*
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • In Vitro Techniques
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy*
  • Rabbits
  • Stroke Volume / drug effects
  • Ventricular Fibrillation / complications
  • Ventricular Fibrillation / drug therapy*


  • Anti-Arrhythmia Agents
  • Dantrolene