Ceconi C, Curello S, Cargnoni A, Boffa G M, Ferrari R
University of Brescia, Italy.
Cardioscience. 1990 Sep;1(3):191-8.
Oxygen-derived free radicals and their metabolites may contribute to the extension of cellular injury that occurs on reperfusion of the ischemic myocardium; and therapy directed against the toxic effects of reactive oxygen species has provided protection to the ischemic myocardium which undergoes subsequent reperfusion. We evaluated the effectiveness of dimercapto-propanol (1,2-dimercapto-propanol, British Anti-Lewisite, dimercaprol) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Dimercaptopropanol is a thiol agent, with two free sulfhydryl groups per molecule, which has no effect on glutathione status nor on the total tissue thiol pool. Pretreatment of the hearts with 10(-6) M dimercapto-propanol resulted in marked myocardial protection, measured in terms of preserved mechanical function and reduced creatine kinase release. On reperfusion less oxidative stress developed. The beneficial effects of dimercapto-propanol could not be explained by hemodynamic differences or effects on energy metabolism. In addition, it is unlikely that dimercapto-propanol acts as a free radical scavenger at the concentrations employed. The protection may be achieved by the drug keeping some key sulfhydryl groups of functional proteins in the reduced state.
氧衍生的自由基及其代谢产物可能会导致缺血心肌再灌注时发生的细胞损伤的扩大；针对活性氧毒性作用的治疗已为随后经历再灌注的缺血心肌提供了保护。我们评估了二巯丙醇（1,2 - 二巯丙醇，英国抗路易氏剂，二巯基丙醇）在Langendorff灌注兔心脏中限制60分钟严重缺血后再灌注30分钟所导致的心肌损伤程度的有效性。二巯丙醇是一种硫醇剂，每个分子有两个游离巯基，对谷胱甘肽状态和总组织硫醇池均无影响。用10(-6)M二巯丙醇预处理心脏可产生显著的心肌保护作用，这通过保留的机械功能和减少的肌酸激酶释放来衡量。再灌注时产生的氧化应激较小。二巯丙醇的有益作用无法用血流动力学差异或对能量代谢的影响来解释。此外，二巯丙醇在所用浓度下不太可能作为自由基清除剂起作用。这种保护作用可能是通过药物使功能蛋白的一些关键巯基保持在还原状态来实现的。
