title: 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 (DeltaVm) response induced by a strong external electrical field in cardiac cells. We investigated the contribution of electroporation to DeltaVm 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). DeltaVm 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 DeltaVm; 2) postshock diastolic resting potential (RP) elevation; and 3) postshock AP amplitude (APA) reduction. Weak stimuli induced a monotonic DeltaVm response and did not affect the RP level. Strong shocks produced a nonmonotonic DeltaVm response and caused RP elevation and a reduction of postshock APA. The maximum positive and maximum negative DeltaVm 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 DeltaVm 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.
authors.affiliation: Cardiac Bioelectricity Research and Training Center, Dept. of Biomedical Engineering, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-7207, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Nikolski
authors.forename: A T
authors.initials: AT
authors.lastname: Sambelashvili
authors.forename: V I
authors.initials: VI
authors.lastname: Krinsky
authors.forename: I R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000200:Action Potentials; D000818:Animals; D003971:Diastole; D018274:Electroporation; D004597:Electroshock / Q000379:methods; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D055095:Optics and Photonics / Q000295:instrumentation; D011817:Rabbits; D016277:Ventricular Function, Left