0328: Electrotonic modulation of the transmural action potential duration heterogeneity in sheep ventricles

Abstract

Transmural APD heterogeneity is thought to play an important role in homogeneous repolarization of the ventricles. Abnormal heterogeneity of action potential duration (APD) in ventricles is known to contribute to arrhythmogenesis. It has been shown to be modulated by electrotonic influences in small species, yet this finding remains to be confirmed in large mammalians. The goal of the present study was to investigate APD differences between epi- and endocardium depending on the pacing location and after a reduction in intercellular coupling in sheep ventricles. Optical mapping experiments were performed in coronary-perfused wedge preparations from sheep left (LV; N=8) or right ventricles (RV; N=3). The wedges were paced at 2Hz on either the endo- or epicardial surface. We also investigated the effect of carbenoxolone (50 μM) in the RV experiments. In the LV experiments, we observed a significant APD difference between endo- (306.45±18.29ms) and epicardium (276.05±9.87ms) when pacing the endocardium (P<0.01). However, this transmural heterogeneity was lost when pacing the epicardium, with endocardial APDs of 284.10±25.67 ms vs 289.8±36.24 ms at the epicardium. A similar observation was made in the RV with a significant increase in epicardial APD when pacing the epicardium (230.17±11.32 ms) vs the endocardium (217.73±19.50 ms) (P<0.01). Upon perfusion with carbenoxolone epicardial APDs significantly increased by 10% (P<0.01) and the difference in epicardial APD between epicardial and endocardial pacing was no longer significant. In conclusion, we find that the epi- and endocardial APDs are modulated by the activation sequence. Specifically, we observe a significant increase in epicardial vs endocardial APD when pacing the epicardium in both the RV and LV and an associated decrease in transmural APD heterogeneity. This effect was abolished upon perfusion with carbenoxolone indicating a role for electronic currents in modulating transmural APD heterogeneity.