Cardioprotective Effects of the Na + /H + Exchange Inhibitor Cariporide in Patients With Acute Anterior Myocardial Infarction Undergoing Direct PTCA

Abstract

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 Ca ²⁺ 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 (ie, 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 P 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.