PO-01-143 HYPOTHERMIA-INDUCED J-WAVES AND ARRHYTHMIAS ARE ASSOCIATED WITH AN EXACERBATION OF REPOLARIZATION RATHER THAN CONDUCTION HETEROGENEITY IN HUMAN HEARTS

Abstract

The cardiac effects of hypothermia have been studied for many years since the initial discovery of the electrocardiographic J-wave in a case of accidental hypothermia. However, the precise mechanisms underlying the origin of the hypothermic J-wave and associated arrhythmias in man are still debated. A limited number of ex vivo animal studies have focused on the transmural repolarization dispersion, but do not provide global mapping of ventricular activation and repolarization heterogeneities. To map hypothermia-induced electrophysiological changes at a tissue level and study the mechanisms of initiation and maintenance of arrhythmias. Optical mapping experiments were performed on isolated right ventricles (RV) from pigs (N=7) and humans obtained through our organ donation program (N=3 control subjects; N=1 SCN5A BrS-associated mutant subject). Epi- and endocardial (EPI and ENDO) action potential conduction and repolarization properties were assessed at different pacing frequencies and arrhythmias were mapped and quantified at baseline (37°C), during severe hypothermia (29°C), and after a return to normothermia. Hypothermia induced a reversible prolongation of global action potential duration at 80% of repolarization (APD80) in pigs (EPI: +27%, ENDO: +21%; p<0.01) and humans (+45% in both EPI and ENDO), an increase in APD80 dispersion, and steepness of APD restitution curve. Repolarization time dispersion was increased in both species (pigs: +94%, p<0.001 in EPI and +79%, p<0.05 in ENDO; humans: +97% in EPI and +14% in ENDO). The total activation time was significantly prolonged in pigs (EPI: +58%, p<0.001; ENDO: +46%, p<0.01) but not in humans. Arrhythmogenicity was further increased in human ventricles (+43% of spontaneous arrhythmias in pigs versus +100% in humans), which always displayed defibrillation-resistant arrhythmias. In the carrier of a SCN5A mutant, hypothermia additionally potentiated epicardial localized conductive disorders already detected at baseline. Our results indicate that, in humans, and contrary to pigs, the hypothermic J-wave and associated arrhythmogenesis result more from an exacerbation of repolarization rather than conduction heterogeneity. Pre-existing localized conduction heterogeneities within pathological hearts can however contribute to the J-wave phenotype during hypothermia.