Arrhythmogenic substrates in myocardial infarct

Life-threatening ventricular tachyarrhythmias are common clinical complications in ischemic heart diseases, especially infarcted heart. Although electrophysiological mechanisms have been extensively clarified for the genesis of arrhythmias in myocardial infarct, arrhythmogenic substrates in the infarct that eventually lead to electrical derangements are not fully understood. This review focuses on the intracellular calcium ion (Ca2+) dynamics and connexin43 (Cx43) gap junctions that play pivotal roles in excitation/contraction processes and intercellular communication, respectively, in heart muscle cells. Recent development of Ca2+-sensitive fluorescent dyes as well as microscopy imaging techniques has contributed substantially to a more precise understanding of spatiotemporal aspects in the intra- and inter-cellular dynamics of Ca2+ in cardiomyocytes. Ca2+ waves, heterogeneous wave-like elevations of the intracellular Ca2+ concentrations ([Ca2+](i)) that develop under [Ca2+](i)-overloaded conditions of the injured myocardium, play an essential role in arrhythmias, especially in triggered arrhythmias. Alteration of Cx43-mediated electrical coupling, that is, gap junction remodeling that arises at myocyte-myocyte and myocyte-myofibroblast interfaces, would also be an important substrate for arrhythmias, especially re-entrant tachyarrhythmias. Clarification of these substrates would provide not only deeper insights into the upstream events of life-threatening tachyarrhythmias in the infarcted heart but also bases for new therapeutic strategies for cardiovascular diseases.