Barrington P L, Meier C F, Weglicki W B
Cardiovascular Research Program, Oklahoma Medical Research Foundation, Oklahoma City.
J Mol Cell Cardiol. 1988 Dec;20(12):1163-78. doi: 10.1016/0022-2828(88)90596-2.
Oxygen free radicals may participate in a variety of pathological cardiac conditions which are associated with an increased incidence of arrhythmias. However, evidence that free radicals per se can alter the electrical function of the myocardium is not convincing. Physiological solutions containing 3 mM dihydroxyfumaric acid (DHF), a compound known to generate free radicals, were superfused over calcium-tolerant cells isolated from the adult canine ventricle. The time course for changes in transmembrane action potentials was monitored using conventional microelectrode techniques. Changes were observed which could be conveniently segregated into three stages. Initially during superfusion with DHF, the voltage of the action potential plateau became more positive and the action potential duration increased (stage 1). Continued superfusion was associated with the development of both early and delayed afterdepolarizations (stage 2), which occasionally produced triggered beats. Subsequently, some cells failed to repolarize beyond -40 mV following an action potential upstroke. In cells which maintained normal levels of resting membrane potential, early and delayed afterdepolarizations ceased concomitant with the development of an increasingly more negative plateau voltage. Action potential duration decreased and plateau potential "collapsed", eventually merging with the resting level of the membrane potential. Resting membrane potential then gradually depolarized to less than -40 mV and all cells became inexcitable within 6 to 20 min (stages 3). Exposure of cells to xanthine (2 mM): xanthine oxidase (0.01 U/ml), another system known to generate free radicals, produced similar results. Superfusion with DHF solutions containing either superoxide dismutase or catalase delayed the appearance and attenuated the development of the changes in the cardiocyte action potential. The results demonstrate that isolated cardiocytes exposed to free radical generating solutions can undergo changes in their electrophysiological activity that resemble those said to underlie disturbances of cardiac rate and rhythm in the clinical setting.
氧自由基可能参与多种病理性心脏疾病，这些疾病与心律失常发生率增加有关。然而，自由基本身可改变心肌电功能的证据并不令人信服。将含有3 mM二羟基富马酸（DHF）（一种已知可产生自由基的化合物）的生理溶液灌流在从成年犬心室分离的耐钙细胞上。使用传统微电极技术监测跨膜动作电位变化的时间进程。观察到的变化可方便地分为三个阶段。最初在DHF灌流期间，动作电位平台期的电压变得更正，动作电位持续时间增加（阶段1）。持续灌流与早期和延迟后去极化的出现有关（阶段2），后者偶尔会产生触发搏动。随后，一些细胞在动作电位上升后未能复极化至-40 mV以上。在维持静息膜电位正常水平的细胞中，早期和延迟后去极化随着平台电压变得越来越负而停止。动作电位持续时间缩短，平台电位“崩溃”，最终与膜电位的静息水平融合。然后静息膜电位逐渐去极化至小于-40 mV，所有细胞在6至20分钟内变得不可兴奋（阶段3）。将细胞暴露于黄嘌呤（2 mM）：黄嘌呤氧化酶（0.01 U/ml）（另一个已知可产生自由基的系统）产生了类似的结果。用含有超氧化物歧化酶或过氧化氢酶的DHF溶液灌流可延迟心肌细胞动作电位变化的出现并减弱其发展。结果表明，暴露于产生自由基溶液的分离心肌细胞可经历其电生理活动的变化，这些变化类似于临床环境中所说的心率和节律紊乱的基础变化。
