IMPROVEMENT OF CARDIAC-FUNCTION BY ALLOPURINOL IN PATIENTS UNDERGOINGCARDIAC-SURGERY

Allopurinol reduces formation of cytotoxic free radicals during myocar dial ischemia/reperfusion in animals. To evaluate the effect of allopu rinol on cardiac performance and metabolism after coronary bypass in h umans, we divided 33 patients into two groups: 15 patients (controls) received no allopurinol and 18 patients received 200 mg allopurinol in travenously (i.v.) 1 h preoperatively. Hemodynamic measurements were m ade with a triple-lumen thermodilution pulmonary artery catheter befor e cardiopulmonary bypass (CPB), 30 min after completion of CPB and 6 h later in the intensive care unit (ICU). A catheter placed into the co ronary sinus was used for blood sampling for measurement of lactate an d creatine phosphokinase MB. Peripheral blood was obtained for measure ment of xanthine oxidase activity (XO), uric acid, and thiol groups. A myocardial biopsy was taken for measurement of thiol group content an d XO before CPB and after heparin neutralization with protamin (a few minutes after CPB). Treated patients had better recovery of cardiac ou tput (CO) and left ventricular stroke work (LVSW) 30 min and 6 h after completion of CPB than did controls. Allopurinol significantly reduce d plasma XO. Plasma concentrations of uric acid increased significantl y in both groups 30 min after completion of CPB, but the increase in c ontrols was greater (p < 0.02) than with allopurinol. Thiol group leve ls increased (p < 0.05) only in controls. Our results demonstrate impr ovement of cardiac function in coronary artery bypass surgery with all opurinol that is related to its metabolic effects consistent with prot ection against XO catalyzed free radical-mediated injury.