心筋虚血再灌流障害に対する新しいコンセプト

在心肌缺血事件期间给药的几种药物可能对心脏再灌注损伤具有保护作用。采用离体灌注大鼠心脏，研究了三大类药物对再灌注心律失常的影响。第一线的药物是氧自由基清除剂。作为氧自由基清除剂，我们选择了人重组超氧化物歧化酶（SOD）和成人T细胞白血病衍生因子（ADF）。我们发现，SOD和ADF对再灌注性心律失常的抑制作用强度相似，且具有叠加性。综上所述，我们认为氧自由基清除剂对大鼠再灌注损伤具有抑制作用，且SOD和ADF的作用点不同。第二种药物是挥发性麻醉剂。作为挥发性麻醉剂，我们检查了氟烷、安氟烷、异氟烷和七氟烷。所有的挥发性麻醉剂，尤其是氟氯烷，对再灌注引起的心律失常都有有效的保护作用。即使同时给予肾上腺素，氟烷也能减弱再灌注引起的心律失常。第三线药物为静脉麻醉，异丙酚对再灌注性心律失常有抑制作用。一些研究者报道异丙酚有清除氧自由基的作用。尽管再灌注性心律失常的机制仍有待进一步研究，但这可能为保护心脏免受再灌注损伤提供治疗手段。

Several drugs adoministered during myocardial ischemic events may possess cardiac protective properties against reperfusion injuries. Using isolated perfused rat hearts, We have investigated the influence of various drugss belonging to three categories on reperfusion arrhythmias. First line of drugs were oxygen free radical scavengers. As oxygen free radical scavengers we chose human recombinant superoxide dismutase(SOD) and adult T cell leukemia-derived factor(ADF). We found that SOD and ADF had a similar strength of inhibitory effects against the reperfusion-induced arrhythmias and the effects were additive. On these results, we have come to the conclusion that oxygen free radical scavengers inhibit the reperfusion injury and that SOD and ADF have different action point. Second line of drugs were volatile anesthetics. As volatile anesthetics we examined halotahane, enflurane, isoflurane and sevoflurane. All volatile anesthetics, especially halotahane, showed potent protective effects against the reperfusion-induced arrhythmias. Even when epinephrine was given simultaneously, halothane attenuated reperfusion-induced arrhythmias. The third line of drug was intravenous anesthetic, propofol had inhibitory effects against reperfusion-induced arrhythmias. Several investigaters report that propofol has an oxygen free radical scavenging effects. Although much still remains to be done to reveal the mechanism of reperfusion-induced arrhythmia may lead the therapeutic means to protect hearts against the reperfusion injuries.