Action Potential Duration Gradients Research Articles

Modulation of Ventricular Repolarization by a Premature Stimulus

Recent evidence suggests that ion channels governing the response of action potential duration (APD) to a premature stimulus (ie, APD restitution) are heterogeneously dispersed throughout the heart. However, because of limitations of conventional electrophysiological recording techniques, the effects of restitution in single cells on ventricular repolarization at the level of the intact heart are poorly understood. Using high-resolution optical mapping with voltage-sensitive dyes, we measured APD restitution kinetics at 128 simultaneous sites on the epicardial surface (1 cm2) of intact guinea pig hearts (n = 15). During steady state baseline pacing, APD gradients that produced a spatial dispersion of repolarization were observed. Mean APD was shortened monotonically from 186 +/- 19 ms during baseline pacing (S1-S1 cycle length, 393 +/- 19 ms) to 120 +/- 4 ms as single premature stimuli were introduced at progressively shorter coupling intervals (shortest S1-S2, 190 +/- 15 ms). In contrast, premature stimuli caused biphasic modulation of APD dispersion (defined as the variance of APD measured throughout the mapping field). Over a broad range of increasingly premature coupling intervals, APD dispersion decreased from 70 +/- 29 ms2 to a minimum of 10 +/- 7 ms2 at a critical S1-S2 interval (216 +/- 18 ms), and then, at shorter premature coupling intervals, APD dispersion increased sharply to 66 +/- 25 ms2. Modulation of APD dispersion by premature stimuli was attributed to coupling interval-dependent changes in the magnitude 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 kinetics were closely associated with longer baseline APD. This relationship explained the reversal of APD between single cells, inversion of APD gradients across the heart, and ECG T-wave inversion during closely coupled premature stimulation. Therefore, because of the heterogeneous distribution of cellular restitution kinetics across the epicardial surface, a single premature stimulus profoundly altered the pattern and synchronization of ventricular repolarization in the intact ventricle. This response has important mechanistic implications in the initiation of arrhythmias that are dependent on dispersion of repolarization.

Simulation of T-wave based on a cardiac model of electrical activity: Effects of anisotropy of excitation propagation and nonlinear ventricular gradient of action potential duration

Simulation of T-wave based on a cardiac model of electrical activity: Effects of anisotropy of excitation propagation and nonlinear ventricular gradient of action potential duration

Nonuniform action potential durations at different sites in canine left ventricle.

We studied the action potential duration (APD) of isolated ventricular muscle fibers. Action potentials were recorded from four different sites (endocardium and epicardium at the apex and the base) in the canine left ventricle by microelectrode techniques. Action potentials from endocardial and corresponding epicardial specimens, and the differential potential between them were recorded simultaneously. The APDs at 60% and 90% repolarization (APD60 and APD90) were measured during superfusion with normal (K+ = 2.7 mM) and altered (K+ = 5.4 mM) Tyrode's solutions. Results were: 1) the distributions of APDs agreed with previous descriptions from in vivo studies; 2) endo-epicardial APD gradients were different between the apex and the base, and apico-basal APD gradients were different between endocardium and epicardium; 3) the shapes of the differential potentials in normal and altered Tyrode's solution were similar to the electrocardiographic T wave form in normal and in mild hyperkalemia. It was concluded that nonhomogeneous APDs may be due to the inherent characteristics of cardiac muscle and the nonuniform endo-epicardial APD gradient helps to account for the genesis of the electrocardiographic T wave form.