title: Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury.
abstract: OBJECTIVE
  Ventilator-induced lung injury (VILI) leads to airway epithelial cell apoptosis and lung inflammation. High tidal volume ventilation in vivo has been shown to induce MIP-2 production, lung neutrophil sequestration and apoptotic airway cell death. This study aimed to determine the effect of N-acetylcysteine (NAC), a scavenger of oxygen radicals, on lung inflammation and apoptosis in an in vivo model of VILI.
  
  
  METHODS
  Sprague-Dawley rats (n = 5 per group) were ventilated at low tidal volume (V(T) 7 mL/kg) or high tidal volume (V(T) 20 mL/kg) with or without administration of 140 mg/kg of intravenous NAC. Animals were ventilated for 30 min, 1 or 2 h, then allowed to recover for 2 h, at which time neutrophil infiltration, MIP-2, TNF-alpha and IL-6 in BAL fluid, as well as the percentage of apoptotic airway epithelial cells, were measured.
  
  
  RESULTS
  Ventilation at V(T) 20 mL/kg increased oxidant release, as measured by serum isoprostane, and decreased lung glutathione, the major antioxidant in the lung. NAC treatment during ventilation at V(T) 20 mL/kg prevented the decrease in lung glutathione and significantly lowered serum isoprostane levels, neutrophil infiltration, cytokines in the BAL and apoptosis in the airways as compared with animals ventilated at V(T) 20 mL/kg without NAC (P < 0.05).
  
  
  CONCLUSIONS
  These data point to an early role of oxidant-induced inflammation and apoptosis in VILI.
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA. osyrkina@partners.org
authors.forename: Olga
authors.initials: O
authors.lastname: Syrkina
authors.forename: Behrouz
authors.initials: B
authors.lastname: Jafari
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hales
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Quinn
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D016166:Free Radical Scavengers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione; D000111:Acetylcysteine