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Blunted Proarrhythmic Effect of Nicorandil in a Langendorff‐Perfused Phase‐2 Myocardial Infarction Rabbit Model
Author(s) -
LEE HUILING,
CHANG POCHENG,
CHOU CHUNGCHUAN,
WO HUNGTA,
CHU YEN,
WEN MINGSHIEN,
YEH SANJOU,
WU DELON
Publication year - 2013
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/pace.12029
Subject(s) - nicorandil , medicine , cardiology , ventricular fibrillation , myocardial infarction , optical mapping
Background Nicorandil (a K ATP 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 Ca 2+ (Ca i ) 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 Ca i 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 K ATP protein expression, which was functionally correlated to the blunted APD shortening response to nicorandil. Conclusions K ATP expression is down‐regulated in phase‐2 MI hearts. Nicorandil restores APD, increases the rate of Ca i reuptake, and flattens CV restitution to suppress spatially discordant alternans induction, which ameliorates its proarrhythmic effects during phase‐2 MI.