title: High oxygen concentrations predispose mouse lungs to the deleterious effects of high stretch ventilation.
abstract: Mechanical ventilation is a necessary intervention for patients with acute lung injury. However, mechanical ventilation can propagate acute lung injury and increase systemic inflammation. The exposure to >21% oxygen is often associated with mechanical ventilation yet has not been examined within the context of lung stretch. We hypothesized that mice exposed to >90% oxygen will be more susceptible to the deleterious effects of high stretch mechanical ventilation. C57B1/6 mice were randomized into 48-h exposure of 21 or >90% oxygen; mice were then killed, and isolated lungs were randomized into a nonstretch or an ex vivo, high-stretch mechanical ventilation group. Lungs were assessed for compliance and lavaged for surfactant analysis, and cytokine measurements or lungs were homogenized for surfactant-associated protein analysis. Mice exposed to >90% oxygen + stretch had significantly lower compliance, altered pulmonary surfactant, and increased inflammatory cytokines compared with all other groups. Our conclusion is that 48 h of >90% oxygen and high-stretch mechanical ventilation deleteriously affect lung function to a greater degree than stretch alone.
authors.affiliation: Departments of Physiology and Pharmacology, Obstetrics and Gynaecology, and Medicine, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada N6A 4V2. tbailey2@uwo.ca
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Bailey
authors.forename: Erica L
authors.initials: EL
authors.lastname: Martin
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism*; D008170:Lung Compliance / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000008:administration & dosage / Q000633:toxicity*; D010101:Oxygen Consumption / Q000502:physiology*; D010713:Phosphatidylcholines / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012121:Respiration, Artificial / Q000009:adverse effects*; D007507:Therapeutic Irrigation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen