Human cardiomyocytes are more susceptible to irreversible electroporation by pulsed electric field than human esophageal cells

Abstract

Pulse electric field-based (PEF) ablation is a technique whereby short high-intensity electric fields inducing irreversible electroporation (IRE) are applied to various tissues. Here, we implemented a standardized in vitro model to compare the effects of biphasic symmetrical pulses (100 pulses, 1-10 μs phase duration (d), 10-1000 Hz pulse repetition rate (f)) using two different human cellular models: human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and human esophageal smooth muscle cells (hESMCs) cultured in monolayer format. We report the PEF-induced irreversibly electroporated cell monolayer areas and the corresponding electric field thresholds (EFTs) for both cardiac and esophageal cultures. Our results suggest marked cell type specificity with EFT estimated to be 2-2.5 times lower in hiPSC-CMs than in hESMCs when subjected to identical PEF treatments (e.g., 0.90 vs 1.85 kV/cm for the treatment of 100 pulses with d = 5 μs, f = 10 Hz, and 0.65 vs 1.67 kV/cm for the treatment of 100 pulses with d = 10 μs, f = 10 Hz). PEF treatment can result in increased temperature around the stimulating electrodes and lead to unanticipated thermal tissue damage that is proportional to the peak temperature rise and to the duration of the PEF-induced elevated temperatures. In our study, temperature increases ranged from less than 1°C to as high as 30°C, however, all temperature changes were transient and quickly returned to baseline and the highest observed ∆T returned to 50% of its maximum recorded temperature in tens of seconds.