0298 : Action potential shortening in the pig right ventricular outflow tract epicardium

Abstract

The right ventricular outflow tract (RVOT) has a distinct embryological origin from the rest of the right ventricle (RV) and is a frequent origin for idiopathic and disease-related arrhythmias. We hypothesised that heterogeneous action potential duration (APD) across the right ventricle (RV) may contribute to RVOT arrhythmia generation. Pigs were anesthetized and monophasic action potentials (MAPs) recorded in sinus rhythm from the epicardium of the RV free wall and RVOT. The RV was isolated and perfused via both right and left anterior coronary arteries. The preparation was paced (1-5Hz) and the electrical activity optically mapped (di-4-ANEPPS, 10μM) on both epicardial (EPI) and endocardial (ENDO) surfaces. The expression of potassium channels was assessed by RT-PCR. In vivo, MAP durations measured at 20% and 80% repolarization were both significantly shorter in the RVOT than in the RV free wall EPI (P<0.05). Similar APD variations were observed ex vivo as RVOT APD20 and APD80 were decreased by 29% and 15% respectively compared to free wall (P<0.01). Interestingly, no APD difference was observed on the ENDO resulting in a larger transmural APD difference in the RVOT than in the RV free wall. The RVOT EPI APD80 shortening was preserved over a range of stimulation frequencies leading to a downward shift of the restitution curve and a significant decrease of its slope (P<0.05). In accordance with these results, expression level of mRNA coding for Kv4.3 (Ito) and Kv11.1 (IKr) were upregulated in the RVOT compared to the RV free wall epicardium (P<0.01) while no difference was found for Kv7.1 (IKs) or Kv4.2 (Ito). Moreover, no variation in K+ channel expression was observed across the RV endocardium. Action potentials are shorter in the RVOT than elsewhere in the RV EPI. This electrophysiological signature was mirrored by regional variations in specific K+ channels. The resulting APD dispersion may facilitate RV re-entrant arrhythmias in the context of a RVOT ectopy.