Disclosures: The authors have no conflicts of interest to disclose.
Blunted Proarrhythmic Effect of Nicorandil in a Langendorff-Perfused Phase-2 Myocardial Infarction Rabbit Model
Article first published online: 4 NOV 2012
©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.
Pacing and Clinical Electrophysiology
Volume 36, Issue 2, pages 142–151, February 2013
How to Cite
LEE, H.-L., CHANG, P.-C., CHOU, C.-C., WO, H.-T., CHU, Y., WEN, M.-S., YEH, S.-J. and WU, D. (2013), Blunted Proarrhythmic Effect of Nicorandil in a Langendorff-Perfused Phase-2 Myocardial Infarction Rabbit Model. Pacing and Clinical Electrophysiology, 36: 142–151. doi: 10.1111/pace.12029
Funding Sources: National Science Foundation [NSC 97–2314- B–182A–089–MY2 to C.C. Chou], Taiwan.
- Issue published online: 4 FEB 2013
- Article first published online: 4 NOV 2012
- Manuscript Accepted: 21 AUG 2012
- Manuscript Revised: 17 AUG 2012
- Manuscript Received: 27 MAY 2012
- National Science Foundation. Grant Number: NSC 97–2314- B–182A–089–MY2
- Animal studies;
- electrophysiology – basic;
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.
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.
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.
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.