Ventricular repolarization properties are electrotonically modulated by ventricular activation sequence. In previous studies we found that local repolarization at a site was longer when activation was initiated at the site than when activation was initiated at a distance from it or when collision of activation fronts occurred near it. The studies we are proposing will determine the factors responsible for the magnitude of the modulation of repolarization properties by activation order, and the effects of activation sequence dependent changes in repolarization properties on inhomogeneity of those properties. Since inhomogeneity of repolarization properties is a factor in arrhythmia vulnerability we will study the effects of activation sequence induced inhomogeneity of repolarization properties on arrhythmia vulnerability. In addition to the relation to arrhythmias, collision of excitation fronts during both normal and abnormal ventricular excitation is likely to be one of the determinants of the distribution of local repolarization properties. Definition of these effects of collision would contribute to basic physiologic knowledge and is relevant to understanding the physiologic basis of ECG T waveform. Studies will include experiments using isolated superfused tissues, isolated perfused hearts, whole animals and computer simulations. The results will contribute to understanding the mechanism for the dependence of repolarization properties on activation sequence and have clinical implications with regard to ECG waveform and arrhythmia vulnerability.
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