title: Dose-related effects of hyperoxia on the lung inflammatory response in septic rats.
abstract: We evaluated the effects of hyperoxia on pulmonary inflammatory changes in sepsis induced by cecal ligation and puncture (CLP) in rats. Seven groups were studied: sham-operated rats breathing air for 20 or 48 h; CLP breathing air for 20 or 48 h; and CLP + 100% oxygen for 20 h, or 70% oxygen for 48 h, or 100% oxygen intermittently (6 h/d) for 48 h. Video microscopy was used to monitor lung macromolecular leak, microvascular flow velocity, and shear rates, and lung morphometry was used for leukocyte infiltration and solid tissue area. Cell counts, tumor necrosis factor α, and nitrites were determined in peripheral blood and lung lavage fluid. Expression of adhesion molecules in blood leukocytes was evaluated by flow cytometry. Cecal ligation and puncture induced inflammation manifested in leukopenia, left shift, thrombocytopenia, increased expression of L selectin and CD11, increased serum and lavage fluid tumor necrosis factor α and leukocytes, and increased lung tissue area, macromolecular leak, and sequestration of leukocytes. Inhalation of 100% oxygen for 20 h increased nitrites (P < 0.01) and decreased leukocyte count in lavage fluid (P < 0.05) and attenuated lung macromolecular leak and changes in solid tissue area (P < 0.01). Inhalation of 70% oxygen (48 h) attenuated expression of adhesion molecules (P < 0.001) but failed to attenuate markers of lung inflammation. In contrast, intermittent 100% oxygen exerted favorable effects on markers of inflammation, attenuated leukocyte expression of L selectin and CD11 (P < 0.01), decreased pulmonary sequestration of leukocytes (P < 0.001), and ameliorated changes in macromolecular leak (P < 0.01) and lung solid tissue area (P < 0.05). Our data support the beneficial effects of safe subtoxic regimens of normobaric hyperoxia on the systemic and pulmonary inflammatory response following CLP.
authors.affiliation: Department of Neonatology, Carmel Medical Center and The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Waisman
authors.forename: Vera
authors.initials: V
authors.lastname: Brod
authors.forename: Michal A
authors.initials: MA
authors.lastname: Rahat
authors.forename: Bat-Chen
authors.initials: BC
authors.lastname: Amit-Cohen
authors.forename: Nitza
authors.initials: N
authors.lastname: Lahat
authors.forename: Doron
authors.initials: D
authors.lastname: Rimar
authors.forename: Hanni
authors.initials: H
authors.lastname: Menn-Josephy
authors.forename: Miriam
authors.initials: M
authors.lastname: David
authors.forename: Ophir
authors.initials: O
authors.lastname: Lavon
authors.forename: Yuval
authors.initials: Y
authors.lastname: Cavari
authors.forename: Haim
authors.initials: H
authors.lastname: Bitterman
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D018496:Hyperoxia / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019041:L-Selectin / Q000096:biosynthesis / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009573:Nitrites / Q000276:immunology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D010100:Oxygen