title: Hyperoxic condition promotes an inflammatory response during cardiopulmonary bypass in a rat model.
abstract: Systemic inflammatory responses in patients receiving cardiac surgery supported by cardiopulmonary bypass (CPB) significantly contribute to CPB-associated morbidity and mortality. We hypothesized that hyperoxia insufflation aggravates the inflammatory responses and organ damage during CPB. To verify this hypothesis, we investigated the inflammatory responses at high and normal levels of arterial pressure of oxygen (PaO2 ) in the rat CPB model. Rats were divided into a SHAM group, a hyperoxia CPB group (PaO2  > 400 mm Hg), and a normoxia CPB group (PaO2 : 100-150 mm Hg). We measured the serum cytokine levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and biochemical markers (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) before, 60, and 120 min after the initiation of CPB. We also measured the wet-to-dry weight (W/D) ratio of the left lung and performed dihydroethidium (DHE) stain reflecting superoxide generation in the lung and liver tissues 120 min after the CPB initiation. In the hyperoxia group, the pro-inflammatory cytokines and biochemical markers significantly increased during the CPB compared with the SHAM, but such increases were significantly suppressed in the normoxia group. However, the increase in anti-inflammatory cytokines was more suppressed in the hyperoxia group than in the normoxia group. The W/D ratio increased significantly more in the hyperoxia group than in the normoxia group. In addition, the DHE fluorescence predominantly increased in the hyperoxia group compared with that in the normoxia group. These data suggest that it is better to avoid too much oxygen insufflation for attenuating organ damage associated with the superoxide production and inflammatory responses during CPB.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan; Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Tsuchimochi
authors.forename: James T
authors.initials: JT
authors.lastname: Pearson
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takewa
authors.forename: Eisuke
authors.initials: E
authors.lastname: Tatsumi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Taenaka
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D013481:Superoxides
keywords: Cardiopulmonary bypass model; Cytokine; Hyperoxia; Superoxide; Systemic inflammation