title: Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia.
abstract: BACKGROUND
  Mechanical ventilation using tidal volumes around 10 ml/kg and zero positive end-expiratory pressure is still commonly used in anesthesia. This strategy has been shown to aggravate lung injury and inflammation in preinjured lungs but not in healthy lungs. In this study, the authors investigated whether this strategy would result in lung injury during transient endotoxemia in the lungs of healthy animals.
  
  
  METHODS
  Volume-controlled ventilation with a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was applied in two groups of anesthetized-paralyzed rabbits receiving either intravenous injection of 5 mug/kg Escherichia coli lipopolysaccharide (n = 10) or saline (n = 10) 2 h after the start of mechanical ventilation. The third group consisted of 10 spontaneously breathing anesthetized animals receiving lipopolysaccharide. Anesthesia was then continued for 4 h in the three groups while the ventilatory modes were maintained unchanged. Lung injury was studied using blood gases, respiratory physiologic variables, analysis of the bronchoalveolar lavage cell counts, and cytokine concentrations and lung pathologic examination.
  
  
  RESULTS
  Significant histologic lung alterations, hypoxemia, and altered lung mechanics were observed in rabbits treated with mechanical ventilation and intravenous lipopolysaccharide but not in the mechanically ventilated animals injected with saline or in spontaneously breathing animals treated with lipopolysaccharide. Endotoxemic ventilated animals also had significantly more lung inflammation as assessed by the alveolar concentration of neutrophils, and the concentrations of the chemokines interleukin 8 and growth-related oncogen alpha.
  
  
  CONCLUSIONS
  These results showed that positive-pressure mechanical ventilation using a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was harmful in the setting of endotoxemia, suggesting that the use of this ventilator strategy in the operating room may predispose to lung injury when endotoxemia occurs.
authors.affiliation: Laboratoire de Physiopathologie Respiratoire (EA 2201) Institut Jean Roche, Faculté de Médecine, Université de la Méditerranée, and Centre Hospitalier Universitaire (CHU) Nord, Marseille, France. fabienne.bregeon@ap.hm.fr
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brégeon
authors.forename: Stéphane
authors.initials: S
authors.lastname: Delpierre
authors.forename: Bruno
authors.initials: B
authors.lastname: Chetaille
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: Amapola
authors.initials: A
authors.lastname: Autillo-Touati
authors.forename: Yves
authors.initials: Y
authors.lastname: Jammes
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pugin
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology*; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D012129:Respiratory Function Tests
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides