Effects of electroporation on optically recorded transmembrane potential responses to high-intensity electrical shocks

Abstract

The outcome of defibrillation shocks is determined by the nonlinear transmembrane potential (Δ Vm) response induced by a strong external electrical field in cardiac cells. We investigated the contribution of electroporation to Δ Vm transients during high-intensity shocks using optical mapping. Rectangular and ramp stimuli (10–20 ms) of different polarities and intensities were applied to the rabbit heart epicardium during the plateau phase of the action potential (AP). Δ Vm were optically recorded under a custom 6-mm-diameter electrode using a voltage-sensitive dye. A gradual increase of cathodal and well as anodal stimulus strength was associated with 1) saturation and subsequent reduction of Δ Vm; 2) postshock diastolic resting potential (RP) elevation; and 3) postshock AP amplitude (APA) reduction. Weak stimuli induced a monotonic Δ Vm response and did not affect the RP level. Strong shocks produced a nonmonotonic Δ Vm response and caused RP elevation and a reduction of postshock APA. The maximum positive and maximum negative Δ Vm were recorded at 170 ± 20 mA/cm2 for cathodal stimuli and at 240 ± 30 mA/cm2 for anodal stimuli, respectively (means ± SE, n = 8, P = 0.003). RP elevation reached 10% of APA at a stimulus strength of 320 ± 40 mA/cm2 for both polarities. Strong ramp stimuli (20 ms, 600 mA/cm2) induced a nonmonotonic Δ Vm response, reaching the same largest positive and negative values as for rectangular shocks. The transition from monotonic to nonmonotonic morphology correlates with RP elevation and APA reduction, which is consistent with cell membrane electroporation. Strong shocks resulted in propidium iodide uptake, suggesting sarcolemma electroporation. In conclusion, electroporation is a likely explanation of the saturation and nonmonotonic nature of cellular responses reported for strong electric stimuli.