PO-705-01 ACTION POTENTIAL RESTITUTION CURVES OBTAINED FROM FULL EXPLANTED HUMAN HEARTS

Abstract

Much of dynamics and stability of electrical waves in the heart is attributed to action potential restitution curve. These curves have been used to investigate how changes in periods of stimulation can lead to the induction of alternans and the initiation of electrically driven arrhythmias. To date, there have been only obtained a few restitution curves from clinical measurements in human hearts using MAPs, or from single human cardiac cells. To obtain the first in tissue action potential duration (APD) restitution curves across large areas of human cardiac tissue. We studied three arterially-perfused whole explanted human hearts (two from recipient patient and one from a rejected donor) using simultaneous voltage and calcium optical mapping at high spatial and temporal resolutions (256x256 pixels, at 500 Hz) and a large field of view of 6-10 cm2. Voltage was measured across the anterior epicardial RV and LV tissue and the endocardium LV, paced at cycle lengths from 3 second down up to conduction block or induction of VF. We use optical mapping to obtain the voltage signal from a large region of the epicardium and quantify the action potential from each pixel (Panel A) to obtain their APD as a function of cycle length (Panel B) across space (as large as 10cm2). We quantify in detail, for the first time, the bifurcation to period doubling (the period of stimulation at which alternans develops) in human hearts across space which appear at or below 600ms (Panel C). For each pacing cycle length we quantify the values of APD dispersion across the tissue and how much they shift during alternans, between even and odd beats as in Panel D, which shows the shortest period of stimulation before VF induction (346ms for heart 1). APD dispersion across the tissue can vary by up to 100 ms and shift the majority of the values by up to 20ms. Optical mapping of explanted hearts is a powerful tool to quantify the dispersion of voltage and action potential duration across tissue. We present the first quantification of the action potential restitution curve for a large range of period of stimulation including the initiation and window of periods for alternans of action potential which is associated with the development of T-wave alternans.