Liu X, Engelman R M, Rousou J A, Cordis G A, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-9984.
Cardiovasc Drugs Ther. 1992 Aug;6(4):437-43. doi: 10.1007/BF00054194.
Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p less than .05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilities. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.
近期研究表明，血管紧张素转换酶（ACE）抑制剂对心肌缺血再灌注损伤具有有益作用。本研究旨在比较两种含巯基的ACE抑制剂卡托普利和佐芬普利与一种不含巯基的ACE抑制剂福辛普利的心脏保护作用。还检测了这些ACE抑制剂在体外清除氧自由基的功效。采用Langendorff技术灌注离体大鼠心脏，在有或无ACE抑制剂（50微摩尔，15分钟）的情况下进行预灌注，然后使心脏经历30分钟缺血，随后再灌注30分钟。佐芬普利和卡托普利可改善缺血后左心室功能并减少心肌细胞损伤，与对照组相比，左心室压力上升一阶导数的恢复改善以及肌酸激酶释放减少证明了这一点（p<0.05）。只有卡托普利和佐芬普利可显著增加冠脉流量。同样这两种药物也抑制再灌注期间增强的脂质过氧化。尽管缺血后心肌膜磷脂组成未观察到显著差异，但卡托普利和佐芬普利降低了非酯化脂肪酸含量，包括棕榈酸、亚油酸、油酸和花生四烯酸。体外研究表明，卡托普利和佐芬普利能够清除羟自由基。这些结果表明，在三种ACE抑制剂中，两种含巯基的药物卡托普利和佐芬普利具有心脏保护以及自由基清除能力。磷脂降解和脂质过氧化的减轻可能有助于本研究中观察到的保护作用。
