Altered Action Potential Heterogeneity in Hypertrophic Right Ventricles of Rats

Abstract

Hypertrophy of the myocardium causes electrophysiological remodeling and changes in action potential duration (APD). The right ventricle (RV) becomes hypertrophied and fails under conditions of pulmonary artery hypertension (PAH). The current study evaluated changes in APD heterogeneity in a rodent model of PAH.Male Wistar rats were given a single i.p. injection of monocrotaline (60 mg/kg) or an equivalent volume of saline. When clinical symptoms of heart failure became apparent (3-4 weeks later) animals were euthanized and the hearts excised. Electrical activity was optically monitored from the epicardial surface of both ventricles in intact hearts using di-4-ANEPPS. The myocardium was stimulated at basic cycle lengths (BCLs) between 80-160 ms. APD at 80% repolarization (APD80) was calculated at the mid-LV, mid-RV and right ventricular outflow tract (RVOT) regions.At 160 ms BCL, APD80 was significantly longer in hypertrophied compared to sham in both RV regions however 8/9 hypertrophied hearts had a longer APD80 in the RVOT vs. mid-RV, whilst in 11/11 sham hearts the APD80 was shorter in the RVOT. The changes in APD between the two RV regions were significantly different (MCT RVOT - mid-RV +6.6 ± 2.6 ms vs. Sham RVOT - mid-RV −6.8 ± 1.3 ms, p<0.0001 unpaired Student's t-test). APD restitution curves were significantly steeper in the mid-RV and RVOT of hypertrophied hearts than the mid-LV or mid-LV, mid-RV and RVOT of sham hearts.These data show that electrical remodeling in monocrotaline treated RV was heterogenous. These regionally dependant changes in APD may contribute to the pro-arrhythmic state of hypertensive and hypertrophic RVs.Supported by the MRC.