HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yoshitaka Hayashi Yoshiki Sawa Motonobu Nishimura Hajime Ichikawa Shigeaki Ohtake Hikaru Matsuda Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hayashi, Y. Articles by Matsuda, H. Search for Related Content PubMed PubMed Citation Articles by Hayashi, Y. Articles by Matsuda, H. Related Collections Cardiac - pharmacology Extracorporeal circulation Mechanical Circulatory Assistance

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