New Na+-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart

Abstract

Background: Experiments were carried out using the new Na+-H+ exchange inhibitor (3-methylsulfonyI-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na+-H+ exchange in myocardial ischemic and reperfusion injury. Methods and Results: Three groups of rabbit hearts (n=5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37°C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 μmol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2±8.5 mm Hg in group 1 to 17.6±4.5 mm Hg in group 2, P