title: Effects of dantrolene on arrhythmogenicity in isolated regional ischemia-reperfusion rabbit hearts with or without pacing-induced heart failure.
abstract: Dantrolene was reported to suppress ventricular fibrillation (VF) in failing hearts with acute myocardial infarction, but its antiarrhythmic efficacy in regional ischemia-reperfusion (IR) hearts remains debatable. Heart failure (HF) was induced by right ventricular pacing. The IR rabbit model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo in both HF and non-HF groups (n = 9 in each group). Simultaneous voltage and intracellular Ca(2+) (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts. Electrophysiological studies were conducted and VF inducibility was evaluated by dynamic pacing. Dantrolene (10 μM) was administered after baseline studies. The HF group had a higher VF inducibility than the control group. Dantrolene had both antiarrhythmic (prolonged action potential duration (APD) and effective refractory period) and proarrhythmic effects (slowed conduction velocity, steepened APD restitution slope, and enhanced arrhythmogenic alternans induction) but had no significant effects on ventricular premature beat (VPB) suppression and VF inducibility in both groups. A higher VF conversion rate in the non-HF group was likely due to greater APD prolonging effects in smaller hearts compared to the HF group. The lack of significant effects on VPB suppression by dantrolene suggests that triggered activity might not be the dominant mechanism responsible for VPB induction in the IR model.
authors: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linkou District, Taiwan ; Chang Gung University College of Medicine, Taoyuan City, Taiwan.
authors: Chung-Chuan
authors: CC
authors: Chou
authors: Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors: Hui-Ling
authors: HL
authors: Lee
authors: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linkou District, Taiwan ; Chang Gung University College of Medicine, Taoyuan City, Taiwan.
authors: Po-Cheng
authors: PC
authors: Chang
authors: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linkou District, Taiwan.
authors: Hung-Ta
authors: HT
authors: Wo
authors: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linkou District, Taiwan ; Chang Gung University College of Medicine, Taoyuan City, Taiwan.
authors: Ming-Shien
authors: MS
authors: Wen
authors: Division of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Linkou District, Taiwan ; Chang Gung University College of Medicine, Taoyuan City, Taiwan.
authors: San-Jou
authors: SJ
authors: Yeh
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003620:Dantrolene / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D009203:Myocardial Infarction / Q000503:physiopathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D003620:Dantrolene