A large body of detailed information has been accumulated on the pattern of ventricular activation, both in animals and in man. In contrast, strikingly little is known about the pattern of repolarization, with no information available for the human heart. The reason is that current clinical electrophysiologic techniques allow exploration of local myocardial activation, but not of the time course of local myocardial repolarization. This research proposal is based on a newly developed method for recording monophasic action potentials (MAPs) from the in vivo human heart. In vitro validation studies have demonstrated that these MAPs provide accurate measurements of the time course of local repolarization.
The specific aims of this proposal are: 1) To further enhance this new MAP recording technique by developing a multielectrode system; 2) to construct the first two-dimensional maps of depolarization are repolarization of the human ventricle from multiple endocardial and epicardial MAP recordings, acquired during cardiac catheterization and surgery; 3) to examine the relationship between ventricular repolarization gradients and the T wave in the surface electrocardiogram, a first approach towards realization of the """"""""forward solution"""""""" of electrocardiography in man; 4) to test the hypothesis that ventricular repolarization is modulated by the sequence of ventricular activation; 5) to determine the degree of dispersion of repolarization in normal ventricles and to compare it with that in hearts with left ventricular hypertrophy and hypertrophic and dilated cardiomyopathy, and 6) to determine the significance of increased dispersion of repolarization for arrhythmogenesis. In summary, this project plans to establish first and comprehensive data on ventricular repolarization in man, its underlying electrophysiology and pathophysiology, and its relation to T wave genesis and arrhythmia.
