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IMPACT OF ANTIOXIDATIVE TREATMENT ON MYOCARDIAL NUCLEAR FACTOR KAPPA-B REGULATION IN PATIENTS SUBJECTED TO CABG

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F10. IMPACT OF ANTIOXIDATIVE TREATMENT ON MYOCARDIAL NUCLEAR FACTOR KAPPA-B REGULATION IN PATIENTS SUBJECTED TO CABG
Uwe M Fischer, Paschalis Tossios, Albert Antonyan, Reza Raji, Hans Joachim Geissler, Wilhelm Bloch, Uwe Mehlhorn; Cologne, Germany

Objective: Nuclear factor kappa-B (NFkB), a transcription factor, has been indicated to play a role in the development of numerous pathological states such as myocardial ischemia-reperfusion (I/R), apoptosis, and ischemic preconditioning. As both myocardial ischemia and reperfusion (by reactive-oxygen intermediates) can activate NFkB we investigated the impact of the antioxidant N-Acetylcysteine (NAC) on NFkB-regulation in patients subjected to cardioplegic arrest (CA) on cardiopulmonary bypass (CPB).
Methods:
Forty coronary artery surgery patients (66±9[SD] years, 9 women and 31 men) subjected to cardiopulmonary bypass (CPB) and cardioplegic arrest were randomized in a double-blind fashion to receive either NAC (100 mg/kg into CPB prime followed by infusion at 20 mg/kg/h; n=20) or Placebo (n=20). We collected transmural LV biopsies prior to CPB (baseline) and at CPB-end. LV specimen were immuno-cytochemically stained against active NFkB and phosphorylated IkBα (activates NFkB). Staining was quantitatively determined using densitometry and the number of positive capillaries per viewfield (cpv) was counted.
Results:
At CPB-end both NFkB and IkBα were unchanged in endothelial cells of controls compared to baseline (45.6±7.6 vs 49.9±7.1 and 36.8±6.1 vs 47.5±8.6 cpv, p>0.05, respectively). In NAC, NFkB and IkBα in endothelial cells were significantly decreased at CPB-end (19.8±1.7 vs 39.1±4.1 cpv, p<0.001, and 22.1±1.9 vs 38.3±4.4 cpv, p=0.006). In cardiomyocytes, however, there were no changes observed in either group.
Conclusions:
Our data show that antioxidative treatment with NAC decreases NFkB-activity follwing I/R in endothelial cells but not in cardiomyocytes. As NFkB-activity post I/R appears to be mediated by free radicals, antioxidative treatment protects coronary endothelium during CA.


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