HOE-642 (cariporide) alters pH(i) and diastolic function after ischemia during reperfusion in pig hearts in situ

The specific Na+/H+ exchange inhibitor HOE-642 prevents ischemic and reperf usion injury in the myocardium. Although this inhibitor alters H+ ion flux during reperfusion in vitro, this action has not been confirmed during comp lex conditions in situ. Myocardial intracellular pH (pH(i)) and high-energy phosphates were monitored using P-31 magnetic resonance spectroscopy in op en-chest pigs supported by cardiopulmonary bypass during 10 min of ischemia and reperfusion. Intravenous HOE-642 (2 mg/kg; n = 8) administered before ischemia prevented the increases in diastolic stiffness noted in control pi gs (n = 8), although it did not alter the postischemic peak-elastance or pr essure-rate product measured using a distensible balloon within the left ve ntricle. HOE-642 induced no change in pHi during ischemia but caused signif icant delays in intracellular realkalinization during reperfusion. HOE-642 did not alter phosphocreatine depletion and repletion but did improve ATP p reservation. Na+/H+ exchange inhibition through HOE-642 delays intracellula r alkalinization in the myocardium in situ during reperfusion in associatio n with improved diastolic function and high-energy phosphate preservation.