B-po02-026 localized cardiac alternans presage ventricular tachyarrhythmias in ovine chronic myocardial infarction model

Electrophysiological changes due to chronic myocardial infarction (MI) are a known substrate for life threatening ventricular tachyarrhythmias (VT/VF). Evaluate the electrophysiological substrates enabling arrhythmogenesis in an ovine chronic MI model using high resolution ex-vivo optical mapping. We developed a novel chronic MI sheep model by deployment of a coil device in a target coronary artery. The 6 weeks following MI, optical mapping experiments were performed on the endocardium of the left ventricle (LV) which included the MI scar, border zone and surrounding healthy tissue. Langendorff perfused wedge preparations (Fig.1A, n=8) were paced at increasing rates (1Hz-5Hz) until loss of capture or VT/VF induction. 2D action potential duration (APD) and amplitude (APA) maps (Figs.1B-C) were analyzed to gauge the effect of MI on the LV. Optical mapping signals of both healthy and conducting surviving myocardium in the scar region were obtained. At mean frequencies of 2.2±0.5Hz and 3.3±0.1Hz, APA alternans and APD alternans were found in multiple discrete regions and in discordant phases. Prior to VT/VF, conduction in scar tissue was irregular and out of phase with healthy myocardium. Localized APA (n=6/8) and APD (n=5/8) alternans preceded onset of VT/VF (Fig.1D). APA alternans were more prominent and spatially evolved (Fig.1E) with increases in pacing frequency, while APD alternans were sporadic and independent of pacing rate. Mean area of the LV covered by APA alternans increased from 3.6±2.5% at 1Hz to 11.45±1.7% at 5Hz. AP alternans underlie arrhythmogenesis in chronic MI ovine hearts.