title: Mild endotoxemia during mechanical ventilation produces spatially heterogeneous pulmonary neutrophilic inflammation in sheep.
abstract: BACKGROUND
  There is limited information on the regional inflammatory effects of mechanical ventilation and endotoxemia on the production of acute lung injury. Measurement of F-fluorodeoxyglucose (F-FDG) uptake with positron emission tomography allows for the regional, in vivo and noninvasive, assessment of neutrophilic inflammation. The authors tested whether mild endotoxemia combined with large tidal volume mechanical ventilation bounded by pressures within clinically acceptable limits could yield measurable and anatomically localized neutrophilic inflammation.
  
  
  METHODS
  Sheep were mechanically ventilated with plateau pressures = 30-32 cm H2O and positive end-expiratory pressure = 0 for 2 h. Six sheep received intravenous endotoxin (10 ng x kg x min), whereas six did not (controls), in sequentially performed studies. The authors imaged with positron emission tomography the intrapulmonary kinetics of infused N-nitrogen and F-FDG to compute regional perfusion and F-FDG uptake. Transmission scans were used to assess aeration.
  
  
  RESULTS
  Mean gas fraction and perfusion distribution were similar between groups. In contrast, a significant increase in F-FDG uptake was observed in all lung regions of the endotoxin group. In this group, F-FDG uptake in the middle and dorsal regions was significantly larger than that in the ventral regions. Multivariate analysis showed that the F-FDG uptake was associated with regional aeration (P < 0.01) and perfusion (P < 0.01).
  
  
  CONCLUSIONS
  Mild short-term endotoxemia in the presence of heterogeneous lung aeration and mechanical ventilation with pressures within clinically acceptable limits produces marked spatially heterogeneous increases in pulmonary neutrophilic inflammation. The dependence of inflammation on aeration and perfusion suggests a multifactorial basis for that finding. F-FDG uptake may be a sensitive marker of pulmonary neutrophilic inflammation in the studied conditions.
authors.affiliation: Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Eduardo L V
authors.initials: EL
authors.lastname: Costa
authors.forename: Guido
authors.initials: G
authors.lastname: Musch
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.forename: Tobias
authors.initials: T
authors.lastname: Schroeder
authors.forename: R Scott
authors.initials: RS
authors.lastname: Harris
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Jones
authors.forename: Jose G
authors.initials: JG
authors.lastname: Venegas
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Vidal Melo
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D019446:Endotoxemia / Q000000981:diagnostic imaging / Q000473:pathology*; D019788:Fluorodeoxyglucose F18; D007249:Inflammation / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D007958:Leukocyte Count; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D009590:Nitrogen Radioisotopes; D010477:Perfusion; D011014:Pneumonia / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D011175:Positive-Pressure Respiration; D049268:Positron-Emission Tomography; D011652:Pulmonary Circulation / Q000502:physiology; D019275:Radiopharmaceuticals; D012121:Respiration, Artificial / Q000009:adverse effects*; D012756:Sheep
chemical_list: D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18