Inhibition of NF-κB activation can attenuate ischemia/reperfusion-induced contractility impairment via decreasing cardiomyocytic proinflammatory gene up-regulation and matrix metalloproteinase expression

Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, proinflammatory genes arc up-regulated, and nuclear factor (NF)-kappa B is involved in this regulation. We studied whether inactivation of NF-kappa B could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB, attenuate matrix metalloproteinase (NIMP) activation, and prevent cardiac mechanical dysfunction. Rabbits received normal saline (group 1) or curcurnin (70 and 7 mu mol/kg in groups 2 and 3) injection 2 hours before CPB. Total CPB was initiated, and myocardial protection was delivered every 20 minutes for 60 minutes of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 hours before the hearts were harvested. Blood was sampled at various time points. Postoperative expression of myocardial mRNA levels of interleukin 6, monocyte chemoattractant protein-1, and tumor necrosis factor-a, postreperfusion plasma level of troponin 1, and cardiac mechanical dysfunction were significantly decreased in the curcumin groups. The myocardial levels of activated MMP-2 and -9 were also significantly reduced compared with the control group. In conclusion, by inhibiting NF-kappa B activation, the up-regulation of cardiac proinflammatory genes can be ameliorated, and the activation of MMPs can be decreased during CPB, thereby lessening severity of cardiac mechanical dysfunction after global cardiac ischemia/reperfusion injury.