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 degrees 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 (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 micromol/l, (3 h after CPB termination) Group-P vs C; 47.8+/-4.9 vs 51.7+/-5.3 micromol/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-.
Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. hayashi@surg1.med.osaka-u.ac.jp
Yoshitaka
Y
Hayashi
Yoshiki
Y
Sawa
Motonobu
M
Nishimura
Naoto
N
Fukuyama
Hajime
H
Ichikawa
Shigeaki
S
Ohtake
Hiroe
H
Nakazawa
Hikaru
H
Matsuda
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D016166:Free Radical Scavengers; D015850:Interleukin-6; D016209:Interleukin-8; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine