ALLOPURINOL-ENHANCED POSTISCHEMIC RECOVERY IN THE ISOLATED PAT HEART INVOLVES REPLETION OF HIGH-ENERGY PHOSPHATES

The effects of allopurinol (AP) on functional and metabolic recovery o f the isolated rat heart after global ischemia were studied. Hearts we re subjected to aerobic perfusion (30 min), cardioplegic infusion (5 m in), normothermic ischemia (37 min), and reperfusion (50 min) which wa s started with secondary cardioplegic infusion (10 min). AP was inject ed into rats (44 mg/kg body wt ip 2 h before heart excision) and added to cardioplegic solution (2 mM) prior and after ischemia. AP treatmen t significantly improved postischemic recovery of the function and red uced the leakage of lactate dehydrogenase from reperfused hearts. Thes e beneficial effects were accompanied by a better preservation of tiss ue content of ATP, the total adenine nucleotides, phosphocreatine, and the total creatine at the end of reperfusion. Inhibition of xanthine oxidase by AP substantially de creased pre- and postischemic release o f xanthine and uric acid and increased postischemic release of hypoxan thine into the coronary effluent. Despite this, AP treated hearts did not exhibit a reduction in hydroxyl radical adduct formation in the ef fluents at reperfusion assessed by the spin-trap measurements. The res ults suggest that AP may protect the heart from ischemia/reperfusion i njury due to enhanced energy provision rather than by prevention of ox ygen-derived free radical formation. (C) 1994 Academic Press, Inc.