Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response

Objective: Cardiopulmonary bypass (CPB) is known to induce post-bypass systemic inflammatory response. Peroxynitrite (ONOO-) is a potent oxidant formed by a rapid reaction between nitric oxide (NO) and superoxide anion. We hypothesized that ONOO- plays a role in the development of post-bypass systemic inflammatory response and examined the efficacy of ONOO- scavenger in a rat-CPB model. Methods: Adult Sprague-Dawley rats underwent 60 min of CPB (100 ml/kg per min, 34 T). Group-P (n = 10) received 50 mg/kg of ONOO- scavenger, quercetin, intraperitoneally 24 It before the initiation of CPB, and Group-C (n = 10) served as controls. Results: There were significant time-dependent changes in plasma nitrate + nitrite (NOx), the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr: an indicator of ONOO- formation), interleukin (IL)-6, IL-8, and respiratory index (RI). There were significant differences in %NO2-Tyr between the groups both at CPB termination (Group-P vs C; 0.26 +/- 0.07 vs 0.55 +/- 0.11%, P < 0.01) and 3 h after CPB termination (0.65 +/- 0.14 vs 1.46 +/- 0.25%, P < 0.01); whereas there were no significant differences in NOx between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6 +/- 4.3 vs 32.7 +/- 4.1 mumol/l, (3 h after CPB termination) Group-P vs C; 47.8 +/- 4.9 vs 51.7 +/- 5.3 mumol/l). Group-P showed significantly lower plasma IL-6 (176.8 +/- 44.3 vs 302.4 +/- 78.1 pg/ml, P < 0.01), IL-8 (9.45 +/- 1.78 vs 16.42 +/- 2.53 ng/ml, P < 0.01) and RI (1.07 +/- 0.19 vs 1.54 +/- 0.25, P < 0.01) 3 h after CPB termination, though there were no significant differences between the groups at CPB termination. Conclusions: These results suggest that ONOO- plays a crucial role in the development of post-bypass systemic inflammatory response and the pretreatment with quercetin has a potential benefit to avoid deleterious effects of ONOO-. (C) 2004 Elsevier B.V. All rights reserved.