MODULATION OF VENTRICULAR REPOLARIZATION BY A PREMATURE STIMULUS - ROLE OF EPICARDIAL DISPERSION OF REPOLARIZATION KINETICS DEMONSTRATED BYOPTICAL MAPPING OF THE INTACT GUINEA-PIG HEART
Kr. Laurita et al., MODULATION OF VENTRICULAR REPOLARIZATION BY A PREMATURE STIMULUS - ROLE OF EPICARDIAL DISPERSION OF REPOLARIZATION KINETICS DEMONSTRATED BYOPTICAL MAPPING OF THE INTACT GUINEA-PIG HEART, Circulation research, 79(3), 1996, pp. 493-503
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.