Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

Chung Chuan Chou, Shengmei Zhou, Hideki Hayashi, Motoki Nihei, Yen Bin Liu, Ming Shien Wen, San Jou Yeh, Michael C. Fishbein, James N. Weiss, Shien Fong Lin, Delon Wu, Peng Sheng Chen

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31 Scopus citations

Abstract

We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.

Original languageEnglish (US)
Pages (from-to)895-906
Number of pages12
JournalJournal of Physiology
Volume580
Issue number3
DOIs
StatePublished - May 1 2007

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ASJC Scopus subject areas

  • Physiology

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