The influence of cell dimensions on the vulnerability of ventricular myocytes to lethal injury by high-intensity electrical fields

Abstract

Application of high intensity electric fields (HIEF) to the myocardium is commonly used for cardiac defibrillation/cardioversion. Although effective at reversing life-threatening arrhythmias, HIEF may cause myocyte damage due to membrane electropermeabilization. In this study, the influence of cell length and width on HIEF-induced lethal injury was analyzed in isolated rat cardiomyocytes in parallel alignment with the field. The field-induced maximum variation of membrane potential (∆V max ) was estimated with the Klee-Plonsey model. The studied myocyte population was arranged in two group pairs for comparison: the longest vs. the shortest cells, and the widest vs. narrowest cells. Threshold field intensity was significantly lower in the longest vs. shortest myocytes, whereas cell width influence was not significant. The threshold ∆V max was comparable in all groups. Likewise, a significant leftward shift of the lethality curve (i.e., relationship of the probability of lethality vs. field intensity) of the longest cells was observed, evidencing greater sensitivity to HIEF-induced damage. However, the lethality curve as a function of ∆V max was similar in all groups, confirming a prediction of the Klee-Plonsey model. The similar results for excitation and injury at threshold and HIEF stimulation, respectively, indicate that: a) the effect of cell length on the sensitivity to the field would be attributable to differences in field-induced membrane polarization that lead to excitation or lethal electroporation; b) the Klee-Plonsey model seems to be reliable for analysis of cell interaction with HIEF; c) it is possible that increased cell length in hypertrophied hearts enhances myocyte fragility upon defibrillation/cardioversion.

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).…”

Testing electrode suitability for field stimulation of high-threshold biological preparations

“…While the wire is more robust for daily use than the plate, it should be noticed that the metal volume required for its confection is ~76-fold greater, which implies in greater cost. On the other hand, the use of stainless steel and nickel-chrome alloy wires with less than 1 mm diameter is not advisable for E stimulation even of adult cardiomyocytes, which present a relatively low threshold (3-6 V/cm; Gomes et al, 2001;Goulart et al, 2012).…”

“…High intensity E stimulation may also be used to induce electroporation (Goulart et al, 2012;Maswiwat et al, 2008;Oliveira et al, 2008). However, using high E intensities may represent a problem, not only regarding the limited availability of electrical stimulators that can supply the necessary stimulus amplitude, but mainly because of undesirable effects related to the flow of high intensity electrical currents across the stimulating electrodes immersed in an aqueous, saline medium.…”

“…We took as a reference the E Volume 31, Number 3, p. [273][274][275][276]2015 intensity required for suprathreshold stimulation of ventricular cardiomyocytes isolated from neonatal rats, which is much greater than that in adult cells (30 vs. 3-6 V/cm, Gomes et al, 2001;Goulart et al, 2012). …”