Ventricular myocyte injury by high-intensity electric field: Effect of pulse duration

Abstract

Although high-intensity electric fields (HEF) application is currently the only effective therapy available to terminate ventricular fibrillation, it may cause injury to cardiac cells. In this study we determined the relation between HEF pulse length and cardiomyocyte lethal injury. We obtained lethality curves by survival analysis, which were used to determine the value of HEF necessary to kill 50% of cells (E50) and plotted a strength-duration (SxD) curve for lethality with 10 different durations: 0.1, 0.2, 0.5, 1, 3, 5, 10, 20, 35 and 70 ms. For the same durations we also obtained an SxD curve for excitation and established an indicator for stimulatory safeness (stimulation safety factor - SSF) as the ratio between the SxD curve for lethality and one for excitation. We found that the lower the pulse duration, the higher the HEF intensity required to cell death. Contrary to expectations, the highest SSF value does not correspond to the lowest pulse duration but to the one of 0.5 ms. As defibrillation threshold has been described as duration-dependent, our results imply that the use of shorter stimulus duration - instead of the one typically used in the clinic (10 ms) - might increase defibrillation safeness.

High-frequency irreversible electroporation for cardiac ablation using an asymmetrical waveform

“…Our findings are in accordance with the strength–duration relation for the irreversible lesion of cardiomyocytes by high-intensity electric fields as presented by Prado et al [15], in which the strength of the electric field necessary to kill 50% of the cells, E 50 , was fitted to their measured data using E 50 = Kd ^ A + B , in which d is the duration of the applied field, and A = − 0.54, thus indicating a strongly non-linear relation between E 50 and d .…”

“…The starting point for introducing our asymmetric waveform are remarks by, e.g., Son et al indicating that electroporation is characterized by electrical creation of aqueous pores in cell membranes, in which the rate of the formation of these pores is strongly, and non-linearly, dependent on the transmembrane voltage [12, 15].…”

New insight on the relationship between lethal electrical fields versus cardiomyocyte orientation

“…On the other hand, there is a non-linear increase in E T as the angle between cell orientation and E direction increases ( Figure 5). This is in accordance with Klee and Plonsey model (Klee and Plonsey, 1976) and with values already reported in the literature (Bassani et al, 2006;DeBruin and Krassowska, 1999;Goulart et al, 2012;Oliveira et al, 2008;Prado et al, 2016).…”

“…Due to the anisotropic nature of the heart tissue, non-uniform potential gradients are generated, which may expose some regions of the heart to an electrical field (E) as large as 100 V/cm (Yabe et al, 1990). This can lead to depression of electrical and contractile cell functions and even cell death (Oliveira et al, 2008;Prado et al, 2016).…”

“…Eng. 2018 September;34(3): 226-233 227/233 phenomenon depends on the transmembrane potential (V m ) exceeding a certain threshold (Fedorov et al, 2008;Ivorra, 2010;Kotnik et al, 2003;Prado et al, 2016) and the maximum V m variation depends directly on the magnitude of the applied E, cell geometry (cell width and length) and also on the E orientation with respect to the cell major axis, as described by the electromagnetic model proposed by Klee and Plonsey (Klee and Plonsey, 1976). The response of cardiac cells to E application has been receiving much attention from the literature, from the point of view of both physiological aspects involved and for possible clinical applications.…”