Characterization of Experimentally Observed Complex Interplay between Pulse Duration, Electrical Field Strength, and Cell Orientation on Electroporation Outcome Using a Time-Dependent Nonlinear Numerical Model

Abstract

Electroporation is a biophysical phenomenon involving an increase in cell membrane permeability to molecules after a high-pulsed electric field is applied to the tissue. Currently, electroporation is being developed for non-thermal ablation of cardiac tissue to treat arrhythmias. Cardiomyocytes have been shown to be more affected by electroporation when oriented with their long axis parallel to the applied electric field. However, recent studies demonstrate that the preferentially affected orientation depends on the pulse parameters. To gain better insight into the influence of cell orientation on electroporation with different pulse parameters, we developed a time-dependent nonlinear numerical model where we calculated the induced transmembrane voltage and pores creation in the membrane due to electroporation. The numerical results show that the onset of electroporation is observed at lower electric field strengths for cells oriented parallel to the electric field for pulse durations ≥10 µs, and cells oriented perpendicular for pulse durations ~100 ns. For pulses of ~1 µs duration, electroporation is not very sensitive to cell orientation. Interestingly, as the electric field strength increases beyond the onset of electroporation, perpendicular cells become more affected irrespective of pulse duration. The results obtained using the developed time-dependent nonlinear model are corroborated by in vitro experimental measurements. Our study will contribute to the process of further development and optimization of pulsed-field ablation and gene therapy in cardiac treatments.

Occurrence and Composition Patterns of ARGs in Plant-Microbial Synergism Were Negatively Reconstructed by an Electrochemical Technology at Low Temperatures

“…In CK, the proportions of plasmid, chromosomal, and unclassified sequences were 19.46, 79.04, and 1.5%, respectively (Figure b). Also, the proportion of ACCs on plasmids was improved by high voltage (54.51% in H-E-Fe), indicating that the voltage (10 V) did not exceed the lethal intensity of the cell, which may be related to the high resistance and low current caused by the matter-free construction system in this study. Furthermore, electrochemical technology has changed the arrangement of iARGs and MGEs in ecological treatment technology at low temperatures.…”

Determination of lethal electric field threshold for pulsed field ablation in ex vivo perfused porcine and human hearts

“…The mean values of the AR in perpendicular lesions were lower than in parallel lesions for MDT pulses; on the other hand, the AR was higher in perpendicular lesions with the 100 μs pulses. This could be due to the differing effects that the pulses of different durations have on elongated cells (78,99). The results suggest that MDT pulse protocol, with its shorter pulse duration and biphasic pulses, resulted in lesions that were less dependent on fiber orientations than the treatment with longer pulse duration.…”

Opportunities and Challenges in Catheter-Based Irreversible Electroporation for Ventricular Tachycardia

“…Dose-response assessments have been generated for isolated rodent ventricles [ 49 ]. In addition to differences in population thresholds, in silico models are optimized to maximize myocytes’ toxicity based on cell orientation relative to the electric field [ 50 ] and tissue fiber orientations [ 51 ].…”