Okabe E, Takahashi S, Norisue M, Manson N H, Kukreja R C, Hess M L, Ito H
Department of Pharmacology, Kanagawa Dental College, Japan.
Eur J Pharmacol. 1993 Jun 1;248(1):33-9. doi: 10.1016/0926-6917(93)90022-i.
The purpose of this study was to investigate the effect of the oxidants hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) on the vulnerability of the myocardium to reperfusion-induced arrhythmias following global ischemia. After a 15 min equilibration period with or without experimental intervention, isolated perfused rat hearts in the Langendorff mode were made globally ischemic for 5 min by cross-clamping the aortic line. No dysrhythmias were evoked upon reperfusion at the 5 min global ischemia time period. HOCl or H2O2 were added to the perfusate 5 min into the equilibration period with a total exposure of 10 min. Global ischemia was then induced for 5 min followed by 10 min of reperfusion. A dose-response curve for HOCl (50-200 microM) indicated the development of idioventricular rhythms, in a concentration-dependent way. Furthermore, coronary flow of the hearts exposed to 100 and 200 microM HOCl, at 5 min post-reperfusion, was decreased; methionine (10 microM to 1 mM), an accepted scavenger for HOCl, prevented the responses to 200 microM HOCl, in a concentration-dependent manner. All hearts exposed to 200 microM H2O2 developed ventricular dysrhythmias during the reperfusion period. Coronary flow increased after 5 min of exposure to 200 microM H2O2 and remained elevated during reperfusion. It is concluded that toxic oxygen derived products are capable of increasing the susceptibility of the myocardium to reperfusion induced arrhythmias, and that although the electrical responses to exposure to those two oxidants were similar, the effects on the vasculature were not the same.
本研究的目的是探讨氧化剂次氯酸（HOCl）和过氧化氢（H2O2）对全心缺血后心肌对再灌注诱导性心律失常易感性的影响。在15分钟的平衡期（有无实验干预）后，采用Langendorff模式的离体灌注大鼠心脏通过夹闭主动脉线进行全心缺血5分钟。在全心缺血5分钟时再灌注未诱发心律失常。在平衡期5分钟时将HOCl或H2O2加入灌注液中，总暴露时间为10分钟。然后诱导全心缺血5分钟，接着再灌注10分钟。HOCl（50 - 200微摩尔）的剂量反应曲线表明室性自主节律呈浓度依赖性发展。此外，再灌注5分钟时，暴露于100和200微摩尔HOCl的心脏冠状动脉血流量减少；蛋氨酸（10微摩尔至1毫摩尔）是公认的HOCl清除剂，以浓度依赖性方式阻止了对200微摩尔HOCl的反应。所有暴露于200微摩尔H2O2的心脏在再灌注期间均出现室性心律失常。暴露于200微摩尔H2O2 5分钟后冠状动脉血流量增加，并在再灌注期间保持升高。结论是毒性氧衍生产物能够增加心肌对再灌注诱导性心律失常的易感性，并且尽管对这两种氧化剂暴露的电反应相似，但对血管系统的影响并不相同。
