Cardioprotective effects of the Na+/H+ exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA

Background-Activation of Na+/H+ exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na+/H+ exchange inhibitors can attenuate Ca2+ influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na+/H+ exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA, Methods and Results-One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na+/H+ exchange inhibitor cariporide (HOE 642) (n=49) before reperfusion, Global and regional left ventricular functions were analyzed by use of paired contrast left ventriculograms performed before and 21 days after PTCA and myocardial enzymes tie, creatine kinase [CK], CK-MB, and LDH) as markers for myocardial tissue injury were evaluated. At follow-up, the ejection fraction was higher (50% versus 40%; P<0.05) and the end-systolic volume was lower (69.0 versus 97.0 mt; P<0.05) in the cariporide group, Significant improvements in some indices of regional wall motion abnormalities were observed, such as the percentage of chords with hypokinesis < -2 SD (P=0.045) and the severity of hypokinesis in the border zone of the infarct region (P=0.052). In addition, CK, CK-MB, or LDH release was significantly reduced in the cariporide patients. Conclusions-Our findings suggest that inhibition of Na+/H+ exchange by cariporide may attenuate reperfusion injury and thereby improve the recovery from left ventricular dysfunction after MI.