Lethal Effect of Electric Fields on Isolated Ventricular Myocytes

Abstract

Defibrillator-type shocks may cause electric and contractile dysfunction. In this study, we determined the relationship between probability of lethal injury and electric field intensity (E in isolated rat ventricular myocytes, with emphasis on field orientation and stimulus waveform. This relationship was sigmoidal with irreversible injury for E > 50 V/cm . During both threshold and lethal stimulation, cells were twofold more sensitive to the field when it was applied longitudinally (versus transversally) to the cell major axis. For a given E, the estimated maximum variation of transmembrane potential (Delta V(max)) was greater for longitudinal stimuli, which might account for the greater sensitivity to the field. Cell death, however, occurred at lower maximum Delta V(max) values for transversal shocks. This might be explained by a less steep spatial decay of transmembrane potential predicted for transversal stimulation, which would possibly result in occurrence of electroporation in a larger membrane area. For the same stimulus duration, cells were less sensitive to field-induced injury when shocks were biphasic (versus monophasic). Ours results indicate that, although significant myocyte death may occur in the E range expected during clinical defibrillation, biphasic shocks are less likely to produce irreversible cell injury.

Electroporation induced by internal defibrillation shock with and without recovery in intact rabbit hearts

“…Theoretical models of electroporation suggest that cell membranes can close small and midsized holes (8), and cell studies have shown this recovery occurring over seconds to minutes (4,37). However, cell membranes are unable to recover following severe electroporation injury, leading to cell death (10). Recent findings suggest that the cardioprotective effects of ICDs in decreasing SCD may not affect total mor-tality, due to increased HF deaths (16).…”

System for open-chest, multidirectional electrical defibrillation

“…The sensitivity of cardiac cells to both kinds of effect markedly depends on the direction of the field application with respect to the cell or fiber bundle major axis: lower field intensities are required Table 1. to produce both excitation and cell injury when the field direction is parallel to the major axis. This seems to be due to the direction-dependent ability of the field to cause a variation in transmembrane electrical potential sufficient for attainment of the excitation threshold or massive electroporation (Bassani et al, 2006;Goulart et al, 2012;Knisley and Baynham, 1997;Oliveira et al, 2008;). As in the whole heart the muscle fibers are arranged in different directions (Smerup et al, 2009), a shock applied between a pair of electrodes in a given orientation will have different impact on cells with different spatial orientations.…”

“…Although the minimum electrical field required for successful defibrillation is estimated as 3-9 V/cm (Malmivuo and Plonsey, 1995), during defibrillation the field may reach ~100 V/cm near the electrodes (Kroll and Swerdlow, 2007;Yabe et al, 1990), which is higher than the threshold values for membrane electroporation (> 25 V/cm, Cheek and Fast, 2004) and cell death (> 50 V/cm; Goulart et al, 2012;Oliveira et al, 2008).…”

“…Nonetheless, exposure to high-intensity electrical fields may cause harmful effects on the heart muscle, attributed to electrical cell membrane damage and consequent Ca 2+ overload (Fedorov et al, 2008;Krauthamer and Jones, 1997;Oliveira et al, 2008;Yabe et al, 1990). Although the minimum electrical field required for successful defibrillation is estimated as 3-9 V/cm (Malmivuo and Plonsey, 1995), during defibrillation the field may reach ~100 V/cm near the electrodes (Kroll and Swerdlow, 2007;Yabe et al, 1990), which is higher than the threshold values for membrane electroporation (> 25 V/cm, Cheek and Fast, 2004) and cell death (> 50 V/cm; Goulart et al, 2012;Oliveira et al, 2008).…”

“…Optimizing the direction of stimulation might decrease the field intensity required for effective stimulation, since, for field application parallel to the cell major axis, the threshold intensity is only 50% of that when the field is applied in the transversal direction (Bassani et al, 2006;Oliveira et al, 2008). A problem of the practical application of this approach to defibrillation is that myocytes are disposed in several directions in the whole heart (Smerup et al, 2009).…”