Blunted Proarrhythmic Effect of Nicorandil in a Langendorff-Perfused Phase-2 Myocardial Infarction Rabbit Model

• Published in: Pacing and clinical electrophysiology Vol. 36; no. 2; pp. 142 - 151
• Main Authors: LEE, HUI-LING, CHANG, PO-CHENG, CHOU, CHUNG-CHUAN, WO, HUNG-TA, CHU, YEN, WEN, MING-SHIEN, YEH, SAN-JOU, WU, DELON
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2013
• Subjects: Animal studies; Animals; Anti-Arrhythmia Agents - therapeutic use; Disease Models, Animal; electrophysiology - basic; Humans; mapping; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Nicorandil - therapeutic use; Perfusion; pharmacology; Rabbits; Treatment Outcome; Ventricular Fibrillation - diagnosis; Ventricular Fibrillation - physiopathology; Ventricular Fibrillation - prevention & control
• ISSN: 0147-8389; 1540-8159
• DOI: 10.1111/pace.12029

Background Nicorandil (a KATP opener) administration is reported to reduce ventricular arrhythmias 4.8 ± 2.2 hours after myocardial infarction (MI). The electrophysiological changes and the effects on dynamic factors and dynamically induced spatially discordant alternans by nicorandil during phase‐2 MI are unclear. Methods Simultaneous voltage and intracellular Ca2+ (Cai) optical mapping was performed in nine Langendorff‐perfused hearts 4–5 hours after coronary artery ligation and nine control hearts. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. Western blot studies (Kir6.1 and Kir6.2) were performed in six more hearts for both groups. Nicorandil (100 μM) was administered after baseline studies. Results Phase‐2 MI hearts showed longer APD, slower conduction velocity (CV), and higher ventricular fibrillation (VF) inducibility than the control hearts. Nicorandil shortened and restored APD without significant arrhythmogenic effects, and also increased the rate of Cai reuptake and flattened CV restitution to suppress spatially discordant alternans, which might account for a tendency toward higher VF threshold with nicorandil infusion in phase‐2 MI hearts. Immunoblotting studies showed significant down‐regulation of KATP protein expression, which was functionally correlated to the blunted APD shortening response to nicorandil. Conclusions KATP expression is down‐regulated in phase‐2 MI hearts. Nicorandil restores APD, increases the rate of Cai reuptake, and flattens CV restitution to suppress spatially discordant alternans induction, which ameliorates its proarrhythmic effects during phase‐2 MI.