Cardiac repolarization. The long and short of it*

Abstract

Abstract Heterogeneity of transmural ventricular repolarization in the heart has been linked to a variety of arrhythmic manifestations. Electrical heterogeneity in ventricular myocardium is due to ionic distinctions among the three principal cell types: Endocardial, M and Epicardial cells. A reduction in net repolarizing current generally leads to a preferential prolongation of the M cell action potential. An increase in net repolarizing current can lead to a preferential abbreviation of the action potential of right ventricular epicardium or left ventricular endocardium. These changes can result in amplification of transmural heterogeneities of repolarization and thus predispose to the development of potentially lethal reentrant arrhythmias. The long QT, short QT, Brugada and catecholaminergic VT syndromes are all examples of pathologies that have very different phenotypes and aetiologies, but share a common final pathway in causing sudden death via amplification transmural or other spatial dispersion of repolarization within the ventricular myocardium. These same mechanisms are likely to be responsible for life-threatening arrhythmias in a variety of other cardiomyopathies ranging from heart failure and hypertrophy, which may involve mechanisms very similar to those operative in long QT syndrome, to isch-aemia and infarction, which may involve mechanisms more closely resembling those responsible for the Brugada syndrome.