Nikolski V P, Sambelashvili A T, Krinsky V I, Efimov I R
Cardiac Bioelectricity Research and Training Center, Dept. of Biomedical Engineering, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-7207, USA.
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H412-8. doi: 10.1152/ajpheart.00689.2003. Epub 2003 Oct 2.
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.
除颤电击的结果取决于心脏细胞中强外部电场诱导的非线性跨膜电位(ΔVm)反应。我们使用光学映射研究了高强度电击期间电穿孔对ΔVm瞬变的贡献。在动作电位(AP)的平台期,将不同极性和强度的矩形和斜坡刺激(10 - 20毫秒)施加于兔心外膜。使用电压敏感染料在定制的6毫米直径电极下光学记录ΔVm。阴极和阳极刺激强度的逐渐增加与以下情况相关:1)ΔVm的饱和及随后的降低;2)电击后舒张期静息电位(RP)升高;3)电击后AP幅度(APA)降低。弱刺激诱导单调的ΔVm反应,且不影响RP水平。强电击产生非单调的ΔVm反应,并导致RP升高和电击后APA降低。阴极刺激的最大正ΔVm和最大负ΔVm分别记录为170±20 mA/cm²,阳极刺激的为240±30 mA/cm²(均值±标准误,n = 8,P = 0.003)。两种极性在刺激强度为320±40 mA/cm²时,RP升高达到APA的10%。强斜坡刺激(20毫秒,600 mA/cm²)诱导非单调的ΔVm反应,达到与矩形电击相同的最大正负值。从单调形态到非单调形态的转变与RP升高和APA降低相关,这与细胞膜电穿孔一致。强电击导致碘化丙啶摄取,提示肌膜电穿孔。总之,电穿孔可能是强电刺激所报道的细胞反应的饱和及非单调性质的一种解释。