BS-516-02 OPTICAL MAPPING OF EXPLANTED HUMAN HEARTS ENABLES REFINED IONIC MODELS OF ACTION POTENTIAL AND CONDUCTION VELOCITY RESTITUTION CURVES FOR ARRHYTHMIA SIMULATION

Abstract

Dynamics and stability of electrical waves in the heart has been attributed to the action potential duration (APD) restitution curve, which is a measure of how the tissue responds to a given cycle length (CL) and the conduction velocity (CV). The restitution curves have been used to investigate how changes in stimulation CL can lead to the induction of alternans and arrhythmias. Only few restitution curves are available from clinical measurements in human hearts, and they were generated using monophasic action potential measurements or from single human cardiomyocytes. To obtain APD and CV restitution curves from explanted human hearts with optical mapping, and take advantage of the experimental data to refine the dynamics of an ionic model, which can be valuable for arrhythmia simulation studies. Optical mapping of membrane potentials was performed on explanted human hearts (n=2 from recipient patients and n=1 from a rejected donor) at high resolutions (256x256 pixels, at 500 Hz) and a large field of view of 8 x 8 cm2. Action potential was measured across the anterior epicardial RV and LV and the endocardium LV, paced at CLs from 3 sec and shorter, until conduction block or VF induction. APD and CV restitution were obtained across the mapped tissue. Optical voltage signals were obtained by pacing the heart at different CLs (Panel A). APDs and CVs were calculated, and restitution curves for APD and CV were calculated for different regions in the hearts. APD alternans, between even and odd beats, were observed and quantified (panels B and C). A human ventricular cardiomyocyte model was fitted to the experimentally obtained APD and CV restitution curves to reproduce AP duration (APD restitution) and conduction velocity (CV restitution) at all CLs. The resultant ionic model recapitulates the experimental data including the bifurcation period and magnitude of alternans as well as the wave propagations. Optical mapping of action potential from explanted human hearts were used to refine the dynamics of an ionic model of human ventricular myocytes. The refined model reproduced the experimental wave propagations at all CLs, including alternans. Our study presents a clinically relevant in silico model to study the induction and dynamics of arrhythmias in whole heart simulations.