Differences in the Electrophysiological Response of Canine Ventricular Epicardium and Endocardium to Ischemia Role of the Transient Outward Current

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Abstract

Background

Acute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (It.) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent I,. in epicardium than in endocardium.

Methods and Results

Isolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20%o shortening in endocardium. 4-Aminopyridine, an I,0 inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of I, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after premature beats. Similar results were obtained in tissues and myocytes obtained from the same myocardial layers, suggesting that the differential sensitivities of epicardium and endocardium to ischemia are largely a result of inherent differences in cellular properties.

Conclusion

Our data suggest that the presence of a prominent It. in epicardium but not endocardium contributes importantly to the selective electrical depression of epicardium by simulated ischemia. The repolarizing influence of It. serves to amplify the ischemia-induced changes in inward (Ica and INa) and outward (calcium-activated) currents. By facilitating loss of the dome in epicardium, I,. contributes to the development of a marked dispersion of repolarization between normal and ischemic epicardium and between epicardium and endocardium, thereby providing the electrophysiological substrate for the genesis of reentrant arrhythmias.

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