MODULATION OF VENTRICULAR REPOLARIZATION BY A PREMATURE STIMULUS - ROLE OF EPICARDIAL DISPERSION OF REPOLARIZATION KINETICS DEMONSTRATED BYOPTICAL MAPPING OF THE INTACT GUINEA-PIG HEART

Recent evidence suggests that ion channels governing the response of a ction potential duration (APD) to a premature stimulus (ie, APD restit ution) are heterogeneously dispersed throughout the heart. However, be cause of limitations of conventional electrophysiological recording te chniques, the effects of restitution in single cells on ventricular re polarization at the level of the intact heart are poorly understood. U sing high-resolution optical mapping with voltage-sensitive dyes, we m easured APD restitution kinetics at 128 simultaneous sites on the epic ardial surface (1 cm(2)) of intact guinea pig hearts (n = 15). During steady state baseline pacing, APD gradients that produced a spatial di spersion of repolarization were observed. Mean APD was shortened monot onically from 186 +/- 19 ms during baseline pacing (S-1-S-1 cycle leng th, 39+/-19 ms) to 120+/-4 ms as single premature stimuli were introdu ced at progressively shorter coupling intervals (shortest S-1-S-2, 190 +/-15 ms). In contrast, premature stimuli caused biphasic modulation o f APD dispersion (defined as the variance of APD measured throughout t he mapping field). Over a broad range of increasingly premature coupli ng intervals, APD dispersion decreased from 70+/-29 ms(2) to a minimum of 10+/-7 ms(2) at a critical S-1-S-2 interval (216+/-18 ms), and the n, at shorter premature coupling intervals, APD dispersion increased s harply to 66+/-25 ms(2). Modulation of APD dispersion by premature sti muli was attributed to coupling interval-dependent changes in the magn itude and direction of ventricular APD gradients, which, in turn, were explained by systematic heterogeneities of APD restitution across the epicardial surface. There was a characteristic pattern in the spatial distribution of cellular restitution such that faster restitution kin etics were closely associated with longer baseline APD. This relations hip explained the reversal of APD between single cells, inversion of A PD gradients across the heart, and ECG T-wave inversion during closely coupled premature stimulation. Therefore, because of the heterogeneou s distribution of cellular restitution kinetics across the epicardial surface, a single premature stimulus profoundly altered the pattern an d synchronization of ventricular repolarization in the intact ventricl e. This response has important mechanistic implications in the initiat ion of arrhythmias that are dependent on dispersion of repolarization.