Buerke M, Rupprecht H J, vom Dahl J, Terres W, Seyfarth M, Schultheiss H P, Richardt G, Sheehan F H, Drexler H
II. Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany.
Am J Cardiol. 1999 May 20;83(10A):19G-22G. doi: 10.1016/s0002-9149(99)00316-1.
Activation of Na+/H+ exchange and subsequent calcium overload in cardiac myocytes appear to play an important role in myocardial tissue injury following ischemia and reperfusion. Results of several in vitro studies in isolated myocytes and heart preparations and in vivo studies in pigs and rats have suggested that inhibition of Na+/H+ exchange is an effective means to prevent lethal reperfusion injury, arrhythmia, and improve myocardial contractile dysfunction. In patients with acute myocardial infarction (MI), any preventive agent is administered immediately before or shortly after reperfusion, rather than before the occurrence of coronary occlusion. The direct interventional approach to treating acute MI provides the opportunity to see if reperfusion has already occurred; if not, a protective agent prior to mechanical reperfusion by percutaneous transluminal coronary angioplasty (PTCA) can be administered to limit reperfusion injury. In a multicenter, randomized, placebo-controlled clinical trial, we tested the hypothesis that inhibition of Na+/H+ exchange with cariporide (HOE 642) could limit infarct size and improve myocardial function in patients with acute transmural MI treated with direct PTCA. Patients were randomized to receive placebo or cariporide given as a 40-mg intravenous bolus prior to reperfusion. Global and regional left ventricular function were analyzed via paired contrast left ventriculograms performed before direct PTCA and after 21 days. Myocardial enzymes (i.e., creatine kinase [CK], CK-MB, and lactate dehydrogenase) as markers for myocardial tissue injury were evaluated as well. The results of this pilot study suggested that the Na+/H+ exchange inhibition could be of benefit to prevent reperfusion injury in patients with acute anterior MI treated with direct angioplasty.
心肌细胞中钠氢交换的激活及随后的钙超载似乎在缺血再灌注后的心肌组织损伤中起重要作用。多项针对分离心肌细胞、心脏标本的体外研究以及针对猪和大鼠的体内研究结果表明，抑制钠氢交换是预防致死性再灌注损伤、心律失常以及改善心肌收缩功能障碍的有效手段。在急性心肌梗死（MI）患者中，任何预防药物都是在再灌注之前或之后不久给药，而不是在冠状动脉闭塞发生之前。治疗急性MI的直接介入方法提供了一个机会，来观察再灌注是否已经发生；如果没有发生，可以在经皮腔内冠状动脉成形术（PTCA）进行机械再灌注之前给予一种保护剂，以限制再灌注损伤。在一项多中心、随机、安慰剂对照的临床试验中，我们检验了这样一个假设：对于接受直接PTCA治疗的急性透壁性MI患者，用卡立泊来德（HOE 642）抑制钠氢交换能够限制梗死面积并改善心肌功能。患者被随机分组，在再灌注前接受安慰剂或40毫克静脉推注的卡立泊来德。通过在直接PTCA之前和21天后进行的配对对比左心室造影分析整体和局部左心室功能。还评估了作为心肌组织损伤标志物的心肌酶（即肌酸激酶[CK]、CK-MB和乳酸脱氢酶）。这项初步研究的结果表明，抑制钠氢交换可能有助于预防接受直接血管成形术治疗的急性前壁MI患者的再灌注损伤。
