Effects of sympathetic stimulation on various repolarization indices in the congenital long QT syndrome

Sympathetic stimulation or catecholamines modulate ventricular repolarization and provoke ventricular tachyarrhythmias in a variety of heart diseases and conditions. Among those, the congenital form of long QT syndrome (LQTS) has long been known to be a Rosetta stone for sympathetic-related ventricular tachyarrhythmias. Recent experimental studies employing arterially-perfused ventricular wedge preparations as well as some clinical studies have greatly advanced our knowledge of the cellular mechanism of the T wave and the various repolarization indices in the ECG, as well as the effect of sympathetic stimulation on these repolarization indices under normal and long QT conditions. Differences in the time course of repolarization of the three predominant cell types, the epicardial, midmyocardial (M), and endocardial cells, across the ventricular wall give rise to voltage gradients responsible for the inscription of normal T waves as well as the manifestation of abnormal T waves in the congenital LQTS. The data from the wedge experiments suggest that the repolarization time of the longest M cell action potential determines the Q-Tend interval, while that of the epicardial action potential determines the Q-Tpeak interval. Therefore, Tpeak-end interval in the ECG may provide an index of transmural dispersion of repolarization (TDR). In this review article, sympathetic stimulation with isoproterenol or epinephrine infusion is demonstrated to modulate differentially these repolarization indices in the ECG as well as the action potentials of the three cells between the LQT1, LQT2, and LQT3 syndromes both experimentally and clinically, explaining the differences in the sensitivity of genotypes of congenital LQTS to sympathetic stimulation.