title: Regional aeration and perfusion distribution in a sheep model of endotoxemic acute lung injury characterized by functional computed tomography imaging.
abstract: OBJECTIVE
  Sepsis-related lung injury is the most common and morbid form of acute lung injury. The objective of this study was to develop an ovine model of septic acute lung injury and characterize its pathophysiology regarding its recruitability and changes in regional aeration and perfusion distributions at injury and during injury evolution.
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  University hospital research laboratory.
  
  
  METHODS
  Adult sheep.
  
  
  METHODS
  Twenty-one anesthetized and mechanically ventilated sheep received intravenous Escherichia coli endotoxin infusion until severe hypoxemia was obtained. Inspiratory- and expiratory-gated computed tomography images of the entire lung were acquired in six subjects at baseline, during endotoxin infusion, and at injury. Perfusion images were obtained at apex and base locations at baseline and injury. Computed tomography images were analyzed for total, air, and tissue lung volumes and axial and vertical aeration and perfusion gradients. Lung recruitability was studied in a subgroup of subjects after injury.
  
  
  RESULTS
  Computed tomography imaging showed a patchy, progressive decrease in air volume as injury evolved, partially replaced by an increase in tissue volume. Perfusion showed a nondependent-to-dependent gradient at baseline that remained relatively unchanged with injury. Perfusion to poorly aerated lung regions was unchanged or increased after injury. Aeration and perfusion distributions at baseline were primarily dorsal or dependent. After injury, the heterogeneity of perfusion and aeration increased and the effect of gravity decreased. Recruitment maneuvers and changes in positive end-expiratory pressure resulted in no improvement in aeration or oxygenation.
  
  
  CONCLUSIONS
  The severe hypoxemia, moderate volume loss, and perfusion patterns are consistent with an injury model in which hypoxemia is exacerbated by endotoxin-mediated failure of hypoxic pulmonary vasoconstriction.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ana.fernandez-bustamante@ucdenver.edu
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Bustamante
authors.forename: R Blaine
authors.initials: RB
authors.lastname: Easley
authors.forename: Matthew
authors.initials: M
authors.lastname: Fuld
authors.forename: Daniel
authors.initials: D
authors.lastname: Mulreany
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.forename: Brett A
authors.initials: BA
authors.lastname: Simon
mesh_terms: D055371:Acute Lung Injury / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides; D008297:Male; D011175:Positive-Pressure Respiration; D011187:Posture; D011652:Pulmonary Circulation; D055425:Respiratory-Gated Imaging Techniques; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D014057:Tomography, X-Ray Computed; D014661:Vasoconstriction
chemical_list: D008070:Lipopolysaccharides