Cottin Y, Doise J M, Maupoil V, Tannière-Zeller M, Dalloz F, Maynadié M, Walker M K, Louis P, Carli P M, Wolf J E, Rochette L
Centre de Cardiologie, CHRU, Dijon, France.
Fundam Clin Pharmacol. 1998;12(2):236-41. doi: 10.1111/j.1472-8206.1998.tb00947.x.
Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H2O2. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24-96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 +/- 0.80 (T0) to 4.57 +/- 1.24 (peak), and decreased to 2.96 +/- 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.7 +/- 7.5 hours. The iron increased significantly from 0.67 +/- 0.34 (T0) to 1.15 +/- 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 +/- 0.28 UI/L at T48 (TO vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.4 +/- 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.
自由基已被认为是参与心肌缺血和再灌注损伤的重要因素。超氧化物能够从铁蛋白中动员铁,释放出的铁可促使过氧化氢生成羟基。本研究的目的是评估通过血浆硫代巴比妥酸反应性物质(TBARS)评估的脂质过氧化随时间的增加情况,以及脂质过氧化与铁状态之间的关系。从17名急性心肌梗死(AMI)男性患者在溶栓治疗前(T0)以及开始纤维蛋白溶解治疗后1、2、3、4、8、12、16、20、24和48小时采集外周静脉血样本。测量TBARS浓度、铁代谢参数、血清肌红蛋白、肌酸激酶和肌酸激酶-MB。通过窦性心动过速(ST)抬高的消退和胸痛的减轻来判断早期再灌注。在溶栓后24 - 96小时通过晚期冠状动脉造影评估冠状动脉再通情况。溶栓治疗后,TBARS水平从2.98±0.80(T0)升高至4.57±1.24(峰值),并在T48时降至2.96±0.40 nmol/mL血浆(T0与峰值:P < 0.001,峰值与T48:P < 0.001,T0与T48:无显著差异)。峰值的平均时间为9.7±7.5小时。铁从0.67±0.34(T0)显著增加至1.15±0.52 mg/L(峰值),并在T48时恢复到再灌注前水平:0.53±0.28 UI/L(T0与峰值:P < 0.001,峰值与T48:P < 0.001,T0与T48:无显著差异)。峰值的平均时间为9.4±7.3小时。反之,血浆肌酸激酶活性、肌红蛋白和铁的增加之间以及生化标志物与纤维蛋白溶解治疗时间之间均未发现相关性。结果证实了溶栓治疗后脂质过氧化与铁状态之间时间关系的重要性。我们的结果与溶栓治疗联合使用抗氧化剂可能有用的概念一致。