Théroux P
Department of Medicine, Montreal Heart Institute and University of Montreal, Quebec, Canada.
Am J Cardiol. 1999 May 20;83(10A):3G-9G. doi: 10.1016/s0002-9149(99)00246-5.
Prevention of myocardial necrosis in acute coronary syndromes is the immediate goal of therapy. Decreasing myocardial oxygen needs is of marginal value. Improving oxygen delivery by mechanical or thrombolytic reperfusion is more successful but still leaves much to be desired in terms of time to reperfusion before damage occurs due to reperfusion itself. During ischemia, there is a metabolic mismatch between glycolysis and glucose oxidation that results in accumulation of hydrogen ions, which, in turn, activates the Na+/H+ exchange system (NHE-1), leading to Na+ and Ca2+ overload and cell death. Blocking NHE-1 is a new strategy designed to prevent or delay cell death. Cariporide, a potent inhibitor of the NHE-1 system, is currently under investigation. Other agents under investigation are designed to modify proton generation, modify proton effects, and attenuate necrosis progression. Also under study are agents designed to mediate preconditioning (adenosine agonists and adenosine triphosphate-sensitive potassium channel openers). Other approaches to minimize cell injury include use of antioxidants and free-radical scavengers, complement inhibitors, selectin blockers, and glycoprotein (GP) IIb/IIIa antagonists.
预防急性冠状动脉综合征中的心肌坏死是治疗的直接目标。降低心肌需氧量的价值不大。通过机械或溶栓再灌注改善氧输送更为成功，但就再灌注损伤发生前的再灌注时间而言，仍有很大的改进空间。在缺血期间，糖酵解和葡萄糖氧化之间存在代谢不匹配，导致氢离子积累，进而激活钠/氢交换系统（NHE-1），导致钠和钙超载以及细胞死亡。阻断NHE-1是一种旨在预防或延迟细胞死亡的新策略。卡里波罗德是一种强效的NHE-1系统抑制剂，目前正在研究中。正在研究的其他药物旨在改变质子生成、改变质子效应并减轻坏死进展。正在研究的还有旨在介导预处理的药物（腺苷激动剂和三磷酸腺苷敏感性钾通道开放剂）。其他尽量减少细胞损伤的方法包括使用抗氧化剂和自由基清除剂、补体抑制剂、选择素阻滞剂和糖蛋白（GP）IIb/IIIa拮抗剂。
