Role of oxidative stress in pathogenesis of coronary spasm, a molecular biological and clinical study

我们研究了还原型谷胱甘肽（GSH），一种重要的抗氧化剂，恢复细胞内氧化还原失衡，防止失活的内皮源性一氧化氮，对痉挛冠状动脉的异常血管反应性的影响。应用定量冠状动脉造影技术测定了24例冠状动脉痉挛性心绞痛（CSA）患者和28例正常对照者冠状动脉内灌注乙酰胆碱（ACh，50μg/min）前和联合灌注GSH（50 mg/min，6 min）或生理盐水（安慰剂）时左冠状动脉心外膜直径的变化。所有的痉挛冠状动脉显示收缩反应ACh，而控制冠状动脉作为一个整体，只有最小的直径变化ACh。GSH输注抑制CSA患者心外膜直径对ACh的收缩反应，而在对照组中无显著影响。盐水输注没有任何影响。结果表明，GSH可减弱CSA患者心外膜冠状动脉对ACh的收缩反应，GSH可能在CSA患者冠状动脉血管功能的调节中起重要作用，氧化低密度脂蛋白（LDL）可损害CSA患者的血管内皮依赖性舒张功能，使冠状动脉收缩。本文采用酶联免疫吸附法（ELISA）测定了37例冠状动脉造影正常的CSA患者和79例正常对照者的血浆Ox-LDL水平，探讨了血浆Ox-LDL水平与CSA的关系。CSA患者血清Ox-LDL水平显著高于对照组。在多变量分析中，较高水平的Ox-LDL是CSA的独立于其他传统危险因素的危险因素。Ox-LDL水平与冠状动脉对乙酰胆碱的收缩反应呈显著正相关。因此，Ox-LDL可能在冠状动脉痉挛的发病机制中发挥作用。

We examined the effect of reduced glutathione (GSH), an important antioxidant which restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spasm coronary arteries. Responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh, 50μg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50mg/min, 6 min) or saline as a placebo in 24 patients with coronary spastic angina (CSA) and in 28 control patients. All of the spasm coronary arteries showed constrictor response to ACh, while the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with CSA, while it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated constrictor response to ACh in epicardial coronary arteries of patients with CSA.GSH may have an important role in the regulation of coronary vasomotor function in patients with CSA.Oxidized low-density lipoproteins (LDL) impair endothelium-dependent dilation and constrict arteries. This study examined possible relation of the circulating plasma levels of Ox-LDL to CSA.The plasma levels of Ox-LDL were measured by ELISA in 37 consecutive patients with CSA and normal coronary angiograms and in 79 consecutive control patients. The Ox-LDL levels in patients with CSA were significantly higher than those in controls. In multivariate analysis, higher levels of Ox-LDL were a risk factor for CSA independently of other traditional risk factors. The Ox-LDL levels had a significant and positive correlation with constrictor response of coronary arteries to the intracoronary acetylchnoline infusion. Thus, Ox-LDL may play a possible role in pathogenesis of coronary spasm.