Impact of antioxidative treatment on nuclear factor kappa-B regulation during myocardial ischemia-reperfusion

Abstract

Nuclear factor kappa-B (NFκB), a transcription factor, plays a role in 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 NFκB, we investigated the impact of the antioxidant N-acetylcysteine (NAC) on NFκB-regulation in patients subjected to cardioplegic arrest (CA) on cardiopulmonary bypass (CPB). Seventeen coronary artery surgery patients (66±9[S.D.] years) 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=9) or placebo (n=8). Transmural LV biopsies were collected prior to CPB (baseline) and at CPB-end and immuno-cytochemically stained against active NFκB and phosphorylated IκBα (activates NFκB). At the end of CPB both NFκB and IκBα 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 counts per viewfield (cpv), P>0.05, respectively). In NAC, NFκB and IκBα 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. Antioxidative treatment with NAC decreases NFκB-activity follwing I/R in endothelial cells. We conclude that NFκB-activity post I/R is mediated by free radicals rather than ischemia alone. © 2006 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.