title: Regional gas exchange and cellular metabolic activity in ventilator-induced lung injury.
abstract: BACKGROUND
  Alveolar overdistension and repetitive derecruitment-recruitment contribute to ventilator-induced lung injury (VILI). The authors investigated (1) whether inflammatory cell activation due to VILI was assessable by positron emission tomography and (2) whether cell activation due to dynamic overdistension alone was detectable when other manifestations of VILI were not yet evident.
  
  
  METHODS
  The authors assessed cellular metabolic activity with [(18)F]fluorodeoxyglucose and regional gas exchange with [(13)N]nitrogen. In 12 sheep, the left ("test") lung was overdistended with end-inspiratory pressure of 50 cm H(2)O for 90 min, while end-expiratory derecruitment of this lung was either promoted with end-expiratory pressure of -10 cm H(2)O in 6 of these sheep (negative end-expiratory pressure [NEEP] group) or prevented with +10 cm H(2)O in the other 6 (positive end-expiratory pressure [PEEP] group) to isolate the effect of overdistension. The right ("control") lung was protected from VILI.
  
  
  RESULTS
  Aeration decreased and shunt fraction increased in the test lung of the NEEP group. [(18)F]fluorodeoxyglucose uptake of this lung was higher than that of the control lung and of the test lung of the PEEP group, and correlated with neutrophil count. When normalized by tissue fraction to account for increased aeration of the test lung in the PEEP group, [(18)F]fluorodeoxyglucose uptake was elevated also in this group, despite the fact that gas exchange had not yet deteriorated after 90 min of overdistension alone.
  
  
  CONCLUSIONS
  The authors could detect regional neutrophil activation in VILI even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting.
authors.affiliation: Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. gmusch@partners.org
authors.forename: Guido
authors.initials: G
authors.lastname: Musch
authors.forename: Jose G
authors.initials: JG
authors.lastname: Venegas
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bellani
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.forename: Tobias
authors.initials: T
authors.lastname: Schroeder
authors.forename: Bodil
authors.initials: B
authors.lastname: Petersen
authors.forename: R Scott
authors.initials: RS
authors.lastname: Harris
authors.forename: Marcos F Vidal
authors.initials: MF
authors.lastname: Melo
mesh_terms: D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007249:Inflammation / Q000209:etiology; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism*; D018375:Neutrophil Activation; D011175:Positive-Pressure Respiration; D049268:Positron-Emission Tomography; D011659:Pulmonary Gas Exchange; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D012756:Sheep; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D019788:Fluorodeoxyglucose F18