Cardioplegia-induced cardiac arrest under cardiopulmonary bypass decreased nitric oxide production which induced cardiomyocytic apoptosis via nuclear factor kappa B activation.

Nitric oxide (NO) prevents the myocardial apoptosis and dysfunction resulting from cardioplegia-induced cardiac arrest (CCA) under cardiopulmonary bypass (CPB). Inasmuch as CCA-induced myocardial dysfunction is associated with acute ischemia/reperfusion (I/R) and inflammatory response, which activates nuclear factor kappaB (NF-kappaB) translocation, we assessed the hypothesis that the detrimental effects of CCA under CPB result from NO imbalance inducing NF-kappaB activation. New Zealand white rabbits (10 in each group, each 2.5-3.5 kg) received total CPB. Rabbits were weaned from CPB and reperfused for 4 h before the hearts were harvested. Blood was sampled at various time points. Nitric oxide donor or NO synthase inhibitor was added into the cardioplegic solution. The ascending aorta was cross-clamped for 60 min, whereas cold crystalloid cardioplegic solution was intermittently infused into the aortic root every 20 min. The myocardia of the reperfused hearts and control hearts were harvested and studied for evidence of apoptosis, I/R-induced proinflammatory gene expression, and inflammatory cytokine production by cardiomyocytes. Pretreatment of the cardiomyocytes with exogenous NO prevented the I/R-induced proinflammatory effects. The inflammatory and apoptotic responses of cardiomyocytes could be lessened by restoring NO concentration via modulation of the (1) nuclear translocation of NF-kappaB, (2) inducible NO synthase mRNA expression, (3) cytochrome c production, and (4) occurrence of apoptosis. Cardioplegia-induced cardiac arrest under CPB can decrease endogenous NO production, which can be restored with exogenous NO supplementation. Exogenous NO can ameliorate the myocardial inflammatory response by inhibition of NF-kappaB translocation, inflammatory gene expression, inducible NO synthase expression, and cytochrome c production.