TY-12533, a novel Na+/H+ exchange inhibitor, prevents myocardial stunning in dogs

Anesthetized open-chest dogs were subjected to 15-min myocardial ischemia f ollowed by 2-h reperfusion to induce myocardial stunning. A novel Na+/H+ ex change inhibitor 6,7,8,9-tetrahydro-2-methyl-5H-cyclohepta[b]pyridine-3-car bonylguanidine maleate (TY-12533), administered 10 min before or 10 min aft er start of ischemia (3 mg/kg/10 min, i.v.), did not affect reductions in r egional myocardial wall thickening, blood flow and pH during ischemia, but it significantly improved recovery of the wall thickening and blood flow af ter reperfusion. These results indicate that TY-12533, even when administer ed during ischemia, could prevent myocardial stunning without affecting myo cardial dysfunction or acidosis induced by brief ischemia. (C) 2001 Elsevie r Science B.V. All rights reserved.