Control of Action Potential Duration Alternans in Canine Cardiac Ventricular Tissue

Abstract

Cardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited spatially-extended alternans elimination in sufficiently large cardiac substrates. However, detailed experimental investigations into the spatial dynamics of alternans control have been restricted to Purkinje fiber studies. A complete understanding of alternans control in the more clinically relevant ventricular tissue is needed. In this paper, we study the spatial dynamics of alternans and alternans control in arterially perfused canine right ventricular preparations using an optical mapping system capable of high-resolution fluorescence imaging. Specifically, we quantify the spatial efficacy of alternans control along 2.5 cm of tissue, focusing on differences in spatial control between different subregions of tissue. We demonstrate effective control of spatially-extended alternans up to 2.0 cm, with control efficacy attenuating as a function of distance. Our results provide a basis for future investigations into electrode-based control interventions of alternans in cardiac tissue.