氨乙基异硫脲对在体家兔缺血/再灌流心肌损伤及自由基生成的影响(英文)

在家兔心脏冠状动脉结扎缺血/再灌流的损伤型模上,采用电子自旋共振(ESR)技术,直接测定整体家兔心肌缺血/再灌流早期自由基信号。自由基清除剂2-β-氨乙基异硫脲(AET)1.7 mg/kg,结扎前15 miniv,能使缺血30 min/再灌流2 min时,缺血心肌中自由基总浓度(10.6±4.1 nmol/g)明显低于对照组(18.0±2.1 nmol/g),而维拉帕米不能明显降低自由基生成量。AET还能减少再灌流期间脂质过氧化产物丙二醛生成量,降低血浆中CK,LDH的含量,改善ECG变化,从而使心肌梗塞的范围由对照组的31±4％降至12±2％。此外,AET可消除致死性室颤的发生。实验结果提示,自由基在缺血/再灌流损伤发生中起重要作用。AET对缩小心肌梗塞范围,消除室颤的发生具有良好的作用,因此可能是一类防治急性心肌梗塞及溶栓治疗或心脏手术后再灌流引起心律失常的有应用价值的新药。

Effects of 2-β-aminoethylisothiourea on free radical generation and myocardial injury induced by ischemia/reperfusion of rabbit heart in vivo

Free radical(FR)generation and myocardial injury were studied in 42 rabbits which underwent 30 minutes ligation of the left ventricular branch(LVB)of the coronary artery followed by rcpcrfusion for various time.The protective effect of 2-β-aminoethylisothiourea(AET,1.7mg/kg,iv,15 min before ligation,n=11),a synthetic FR scavenger,was observed and compared to those of saline control(n=18)and verapamil(0.45 mg/kg,iv 10 min before ligation,n=13).A burst of FR was directly demonstrated by using electron spin resonance spectroscopy in the ischemic zone(IZ)of the control rabbit hearts(18.0±2.0 nmol/g wet wts)at 2 min post reperfusion.The concentration of FR was significantly reduced in IZ of AET treated group(10.6±4.1),which was similar to that in non-ischemic zone(NIZ).Verapamil failed to reduce the generation of FR(15.5±2.7).AET prevented the increase of lipid peroxidation end-product malondialdchyde(MDA)in IZ and significantly reduced the release of creatinc kinase(CK)and lactate dehydrogenase(LDH)into plasma,thus resulting in a reduction of infarct sizes from 30±4 %(control)to 12±2 %(AET).The incidence of fatal ventricular fibrillation(VF)was reduced from 6/18 in control group to 0/11 in AET treated group.The results suggested that FR played an important role in the pathogenesis of post-ischemic reperfusion injury.The benificial effects of AET in the reduction of infarct size and fatal VF indicated that the drug may be useful in the treatment of acute myocardial infarction or prevention of reperfusion arrhythmias in thrombolytic therapy or cardiac surgery.