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Eur J Cardiothorac Surg 2004;26:276-280
© 2004 Elsevier Science NL

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

^a Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
^b Second Department of Physiology, Tokai University School of Medicine, Isehara City, Kanagawa, Japan

Received 13 February 2004; received in revised form 21 March 2004; accepted 22 March 2004.

^* Corresponding author. Address: 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan. Tel.: +81-6-6879-3154; fax: +81-6-6879-3163
e-mail: hayashi{at}surg1.med.osaka-u.ac.jp

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 °C). Group-P (n=10) received 50 mg/kg of ONOO^– scavenger, quercetin, intraperitoneally 24 h before the initiation of CPB, and Group-C (n=10) served as controls. Results: There were significant time-dependent changes in plasma nitrate+nitrite (NO_x), 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 NO_x between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6±4.3 vs 32.7±4.1 µmol/l, (3 h after CPB termination) Group-P vs C; 47.8±4.9 vs 51.7±5.3 µmol/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^–

Key Words: Cardiopulmonary bypass • Nitric oxide • Peroxynitrite • Inflammatory response • Cytokines

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