title: Cellular mechanisms underlying the long QT syndrome.
abstract: QT prolongation is commonly associated with life-threatening torsade de pointes arrhythmias that develop as a consequence of the amplification of electrical heterogeneities intrinsic to the ventricular myocardium. These heterogeneities exist because of differences in the time course of repolarization of the three predominant cell types that make up the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization responsible for the inscription of the electrocardiographic T wave. Agents and conditions that reduce net repolarizing current amplify the intrinsic spatial dispersion of repolarization, thus creating the substrate for the development of re-entry. The result is a prolongation of the QT interval, abnormal T waves, and development of polymorphic re-entrant ventricular tachycardia displaying characteristics of torsades de pointes. These conditions also predispose M cells and Purkinje fibers to develop early afterdepolarization-induced extrasystoles, which are thought to trigger episodes of torsades de pointes. Agents that prolong the QT interval but do not increase transmural dispersion of repolarization are not capable of inducing torsades de pointes. The available data suggest that that the principal problem with the long QT syndrome is not long QT intervals but rather the dispersion of repolarization that often accompanies prolongation of the QT interval.
authors.affiliation: Masonic Medical Research Laboratory, Utica, New York, USA; National Cardiovascular Center, Osaka, Japan. ca@mmrl.edu
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D004562:Electrocardiography; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008133:Long QT Syndrome / Q000188:drug therapy / Q000209:etiology*; D016171:Torsades de Pointes / Q000188:drug therapy / Q000209:etiology
chemical_list: D007473:Ion Channels