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

• DOI: 10.1161/01.cir.101.25.2902
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Hans-Jürgen Rupp...; Jürgen vom Dahl; Wolfram Terres; Karl Melchior Sey...; Gert Richardt; Heinz-Peter Schul...; Michael Buerke; Florence H. Sheehan; Helmut Drexler
• Keywords: Adult; Male; Sodium-Hydrogen Exchangers; Myocardium; Myocardial Infarction; Heart; Middle Aged; Guanidines; Ventricular Function, Left; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Humans; Female; Sulfones; Angioplasty, Balloon, Coronary; Aged

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 (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<0.05) and the end-systolic volume was lower (69.0 versus 97.0 mL;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.