硫辛酸抗再灌期心律失常与外源性自由基所致动作电位异常的作用

EFFECTS OF LIPOIC ACID ON REPERFUSION INDUCED ARRHYTHMIAS AND MYOCARDIC ACTION PO TENTIAL ALTERATIONS INDUCED BY FREE RADICAL GENERATING SYSTEM

用 Langendorff 法灌流大鼠心脏。结扎冠状动脉左前降支10 min,松结再灌3 min。再灌期内对照组心室颤动发生率为100%,正常窦性心律时间缩短至29±56s。给硫辛酸组(6.8×10^(-6)1.7×lO^(-4)mol/L)心室颤动发生率下降至33—50%。正常窦性心律时间延长至97s 以上。用标准微电极技术记录豚鼠乳头肌动作电位(AP)。在黄嘌呤氧化酶(0.004U/ml)与次黄嘌呤(1Oμmol/L)氧自由基发生系统作用后第3min,未给药组 AP 各参数与对照组比较,APA、RP 和 V_(max)分别下降20%(P<0.05),16%(p<0.05)和45%(p<0.01)。给硫辛酸组(3.5×10^(-5)mol/L)AP 各参数的异常明显减轻,与对照组比较,APA,RP 和 V_(max)分别下降9%(p<0.05),9%(P<0.05)和18%(P<0.05)。给药组与未给药组比较,三项指标差别显著。上述结果提示,硫辛酸的自由基清除作用使异常动作电位得到改善,从而降低了心律失常发生率。

By means of Langendorff method the isolated rat heart was perfused with KrebsHenseleit solution.Following ligation of the left decending coronary artery for10 min the heart was reperfused for 3 min.The incidence of ventricular fibrilla-tion in the reperfusion period was 100%,and the normal sinus rhythm time wasshortened to 29 s within 3 min of reperfusion.Administration of lipoic acid(6.8×10^(-6)—1.7×10^(-4) mol/L)to the perfusate significantly reduced the incidenceof ventricular fibrillation to 33-50% and prolonged the normal sinus rhythm timeto 97—107 s.APA,RP,and V_(max)recorded from the guinea pig papillary musclewere depressed due to the deleterious effect of xanthine oxidase and hypoxanthinefree radical generating system.Under the treatment of lipoic acid(3.5×10^(-5)mol/L),the depression of APA,RP,and V_(max)were significantly relieved.Thisconfirms that lipoic acid treatment,owing to its free radical scavenger effect,is ableto protect myocardium from free radical induced electrophysiological abnormali-ties,and consequently decrease the incidence of malignant arrhythmias.