title: Postoperative hyperoxia (60%) worsens hepatic injury in mice.
abstract: BACKGROUND
  Liver damage by ischemia and reperfusion injury is a risk factor for morbidity and mortality after liver surgery. Postoperative oxygen treatment is routinely applied in the postanesthesia and intensive care unit after liver surgery. The risks of aggravating the injury by increasing inspiratory oxygen from 21 to 60% in the postoperative period were investigated in mice.
  
  
  METHODS
  Parameters of liver injury were compared after induction of hepatic ischemia-reperfusion injury, by clamping the left liver lobe for 45 min, and reperfusion for 24 h either under normoxic (21% oxygen) or hyperoxic (60% oxygen) conditions (n=22 per group). The extent of tissue injury and oxidative responses was analyzed in the presence or absence of polymorphonuclear leukocytes, functional Kupffer cells, and the p47phox unit of the nicotinamide adenine dinucleotide phosphate oxidase (n=6 to 11 per group).
  
  
  RESULTS
  Compared with postoperative normoxic conditions, hyperoxia increased cell damage (glutamate-pyruvate transaminase: 1,870 [±968 SD] vs. 60% 2,981 [±1,038 SD], 21 vs. 60% oxygen, in U/l as mean±SD; P<0.01), liver weights (341±52 vs. 383±44, 21 vs. 60% oxygen, in mg as mean±SD; P=0.02), damage scores (1.9±0.8 vs. 3.1±1.0, 21 vs. 60% oxygen, score as mean±SD; P=0.02), and reactive oxygen species (15.0±12.0 vs. 30.4±19.2, 21 vs. 60% oxygen, in μmol/l as mean±SD; P<0.05). The aggravation of the tissue damaging effects as a result of hyperoxia was not seen in mice with depletions of polymorphonuclear leukocytes or Kupffer cells, or with nonfunctioning nicotinamide adenine dinucleotide phosphate oxidase.
  
  
  CONCLUSIONS
  Liver injury after ischemia was significantly aggravated by hyperoxia as a consequence of immune cell-mediated oxidative burst. Further studies are needed to elucidate whether routine delivery of high inspirational oxygen concentrations postoperatively should be limited.
authors.affiliation: From the University Hospital of the Ludwig- Maximilians-University, Department of Anesthesiology, Klinikum Grosshadern, Munich, Germany (Q.Z., A.M., I.K., A.C.); National Institute on Minority Health and Health Disparities, National Institutes of Health, Division of Intramural Research, Bethesda, Maryland (S.H.J.); National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland (A.O., D.L., J.M.W., M.S., A.C.); New England Inflammation and Tissue Protection Institute Consortium at Northeastern University, Boston, Massachusetts (A.O., D.L., M.S.); Mouse Imaging Facility, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland (B.K.); and Department of Anaesthesiology and Intensive Care, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (M.T.).
authors.forename: Quirin
authors.initials: Q
authors.lastname: Zangl
authors.forename: André
authors.initials: A
authors.lastname: Martignoni
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Jackson
authors.forename: Akio
authors.initials: A
authors.lastname: Ohta
authors.forename: Brenda
authors.initials: B
authors.lastname: Klaunberg
authors.forename: Ines
authors.initials: I
authors.lastname: Kaufmann
authors.forename: Dimitry
authors.initials: D
authors.lastname: Lukashev
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
authors.forename: Michail
authors.initials: M
authors.lastname: Sitkovsky
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
authors.forename: Alexander
authors.initials: A
authors.lastname: Choukèr
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology*; D000818:Animals; D022781:Hepatocytes / Q000473:pathology; D018496:Hyperoxia / Q000150:complications* / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000032:analysis; D011183:Postoperative Complications / Q000473:pathology*; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D010100:Oxygen