Effects of activation sequence on the spatial distribution of repolarization properties

The electrotonic effects of activation spread on the spatial distribution of repolarization properties were studied in animal experiments and with computer simulations. Refractory periods (RPs) were measured at 36 sites within a 1.0 cm2 region of the epicardial surface of the canine pulmonary conus during 37 drives in 11 experiments. In each experiment three or four sites along the perimeter of the region bounding the RP test sites were driven. Activation propagated uniformly during some and nonuniformly during other drives in the same animals. In general, RPs were distributed uniformly when activation spread uniformly and nonuniformly when activation spread nonuniformly. The authors observed RP differences as large as 16 ms between sites with 2 mm separation during drive from some epicardial sites in these normal canine hearts. Indices of nonuniformity of activation and of relative RP values were used to quantify the relation between nonuniformity of activation spread and the spatial distribution of the RP. There was a significant negative correlation between nonuniformity of activation and RP indices during the 19 drives in which activation spread nonuniformly. This indicated that RPs were relatively long at sites where activation spread decelerated and relatively short at sites where activation spread accelerated. When nonuniform activation spread was simulated by introducing high-resistance barriers in a model with fixed anisotropic conductivities, there were marked spatial variations in action potential duration. The spatial variations in action potential duration were negatively correlated to acceleration and deceleration of activation spread. The major new finding of this study is that the spatial distributions of RPs are markedly affected by activation spread. Since both characteristics of activation sequence and nonuniformity of RP distributions have roles in reentrant arrhythmias, the findings suggest that some sites of origin of premature activity may be more arrhythmogenic than others. The findings may also explain why ventricular tachycardia can sometimes be initiated from one but not from other sites in patients undergoing electrophysiologic testing.