New Na+-H+ Exchange Inhibitor HOE 694 Improves Postischemic Function and High-Energy Phosphate Resynthesis and Reduces Ca21 Overload in Isolated

Background Experiments were carried out using the new Na+-H+ exchange inhibitor (3-methylsulfonyl-4-piperidi-nobenzoyl)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,umol/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 dur-ing reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 start