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Heterogeneity of cellular repolarization in LQTS: the role of M cells

C. Antzelevitch1

Masonic Medical Research Laboratory, Utica, New York, U.S.A.

1 Correspondence: Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York 13501, U.S.A.

Abstract

QT prolongation, whether congenital or acquired, is commonly associated with life-threatening torsade de pointes (TdP) arrhythmias that develop as a consequence of the amplification of electrical heterogeneities intrinsic to the ventricular myocardium. Electrophysiologic distinctions among the three predominant cell types that comprise the ventricular myocardium are responsible for the normal dispersion of repolarization and transmural voltage gradients that inscribe the J and T waves of the ECG. Differences in the response of epicardial, endocardial and M cells to pharmacologic agents and/or pathophysiological states result in amplification of these intrinsic electrical heterogeneities, thus providing a substrate and trigger for the development of reentrant arrhythmias. Transmural dispersion of repolarization secondary to disproportionate prolongation of the action potential of M cells in response to a reduction in net repolarizing current often leads to the development of a vulnerable window, long QT intervals, abnormal T waves as well as to the induction of polymorphic VT resembling torsade de pointes. The decrease in net repolarizing current also predisposes M cells and Purkinje fibres to develop early afterdepolarization-induced triggered activity, which is responsible for the generation of extrasystoles thought to precipitate TdP. Agents that prolong the QT interval but do not increase transmural dispersion of repolarization are not capable of inducing TdP. Thus, 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.

Key Words: Long QT syndrome • transmural dispersion • repolarization abnormalities • T wave • U wave

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