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


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.


CONCLUSIONS
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.
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chung-Chuan
CC
Chou
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
Ming-Shien
MS
Wen
Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan.
Hui-Ling
HL
Lee
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.
Po-Cheng
PC
Chang
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.
Hung-Ta
HT
Wo
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
San-Jou
SJ
Yeh
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taipei, Taiwan.
Delon
D
Wu
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D005117:Cardiac Complexes, Premature / Q000150:complications / Q000188:drug therapy*; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000502:physiology; D003620:Dantrolene / Q000627:therapeutic use*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000150:complications / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D003620:Dantrolene
calcium; dantrolene; heart failure; myocardial infarction; optical mapping; pharmacology; ventricular fibrillation