Electroporation-Mediated Membrane Permeability as a Driver of Cardioversion: A Computational Study

Abstract

Electrical cardioversion terminates cardiac arrhythmias by delivering direct current. Moreover, strong electrical shocks cause transient permeabilization of biological membranes, i.e., reversible electroporation. This mechanism has been suggested as a contributor to cardioversion. This study investigates whether reversible electroporation alone is sufficient to reproduce cardioversion in silico. External electric field distributions were calculated for a 2D tissue slab by applying a voltage difference across opposite corners. Local pore densities were assigned proportional to the electric field magnitude. Then electroporation-mediated membrane currents were introduced into a mathematical model of the human atrial cardiomyocyte. This modified cell model was embedded into the tissue model of a 2D tissue slab. The previously computed heterogeneous pore distributions were applied to monodomain simulations where reentrant spiral waves had been initiated. Finally, the effect of varying local pore densities and durations to terminate reentries was assessed. Increasing the prescribed pore density resulted in a clear transition from unsuccessful cardioversion to wavefront modification and, ultimately, successful reentry termination. For shocks below 450V, depolarization remained heterogeneous and reentry persisted. In contrast, 500V shocks yielded complete depolarization and termination of reentry. The voltage threshold for reentry termination was highly sensitive to pore resealing kinetics. Despite modeling simplifications, these findings demonstrate that transient membrane permeabilization alone can terminate reentrant activity in atrial tissue models, supporting electroporation as a plausible enabling mechanism in shock-induced arrhythmia termination.