Cardioplegic effect of Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor against ischemia-reperfusion myocardial injury in cardiac surgery

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Ischemic-reperfusion injury has been one of the most serious problem even in current cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury by preventing energy depletion associated with oxidative stress. The purpose of our study was to evaluate the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest.Isolated rat hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution (St.Thomas solution) given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n=8) were perfused with a standard cardioplegic solution and terminal warm cardioplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis.During reperfusion, the 3-AB(+) group showed significantly higher (P=0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK ; P=0.003 GOT ; P<0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P<0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P=0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group.In conclusion, cardioplegic solution supplemented with PARS inhibitor provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress.