Sodium-hydrogen exchange inhibition: Novel strategy to prevent myocardial injury following ischemia and reperfusion

Activation of Na+/H+ exchange and subsequent calcium overload in cardiac my ocytes appear to play an Important sole in myocardial tissue injury followi ng ischemia and reperfusion. Results of several in vitro studies in isolate d myocytes and heart preparations and in vivo studies in pigs and ruts have suggested that inhibition of Na+/H+ exchange is an effective means to prev ent lethal reperfusion injury, arrhythmia, and improve myocardial contracti le dysfunction. In patients with acute myocardial infarction (MI), any prev entive agent is administered immediately before or shortly after reperfusio n, rather than before the occurrence of coronary occlusion. The direct inte rventional approach to treating acute MI provides the opportunity to see if reperfusion has already occurred; if not, a protective agent prior to mech anical reperfusion by percutaneous transluminal coronary angioplasty (PTCA) can be administered to limit reperfusion injury. In a multicenter, randomi zed, placebo-controlled clinical trial, we tested the hypothesis that inhib ition of Na+/H+ exchange with cariporide (HOE 642) could limit infarct size and improve myocardial function in patients with acute transmural MI treat ed with direct PTCA. Patients were randomized to receive placebo or caripor ide given as a 40-mg intravenous bolus prior to reperfusion. Global and reg ional left ventricular function were analyzed via paired contrast left vent riculograms performed before direct PTCA and after 21 days. Myocardial enzy mes (i.e., creatine kinase[CK], CK-MB, and lactate dehydrogenase) as marker s for myocardial tissue injury were evaluated as well. The results of this pilot study suggested that the Na+/ H+ exchange inhibition could be of bene fit to prevent reperfusion injury in patients with acute anterior MI treate d with direct angioplasty.. (C) 1999 by Excerpta Medica, Inc.