title: Evaluating lung injury at increasing time intervals in a murine brain death model.
abstract: BACKGROUND
  Only 15%-25% of brain death (BD) donors match the ideal donor criteria for lung transplantation. Lung injury may evolve in the hours after onset of brain death, but the evolution over time has not been well studied in lung. The aim of this study was to evaluate lung injury at different time points after BD using a murine model.
  
  
  METHODS
  Male C57BL6/J mice (8-10 wk) were anesthetized, tracheotomized, and mechanically ventilated. Mice were randomly assigned to six groups (n=8/group): 1 h, 3 h, and 6 h sham ([SH1], [SH3], [SH6]) and 1 h, 3 h, and 6 h brain death ([BD1], [BD3], [BD6]). BD was gradually induced by a subdural balloon catheter. Heart rate and mean arterial pressure were continuously monitored. At the end of the experiment, bronchoalveolar lavage was performed and the left lung was excised for histopathologic analysis.
  
  
  RESULTS
  The Cushing reflex was characterized by a rapid increase in heart rate and mean arterial pressure after balloon inflation in BD animals. An increase in percentage of neutrophils was seen with a longer follow-up period (P<0.05). Interleukin 6 and interleukin 10 levels in bronchoalveolar lavage progressively increased with longer time intervals after BD ([BD1] versus [BD6]; P<0.01). Histologic signs of lung injury (congestion, hemorrhage, and neutrophilic influx) were more pronounced in [BD3] and [BD6] compared with the other groups; however, this difference did not reach statistical significance.
  
  
  CONCLUSIONS
  Three hours after brain death, significant signs of inflammation and lung injury were seen compared with sham-operated animals. This murine BD model gives us opportunities for further mechanistic studies regarding treatment of BD-related donor lung injury.
authors: Laboratory for Experimental Thoracic Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Shana
authors: S
authors: Wauters
authors: Jana
authors: J
authors: Somers
authors: Stephanie
authors: S
authors: De Vleeschauwer
authors: Erik
authors: E
authors: Verbeken
authors: Geert M
authors: GM
authors: Verleden
authors: Johannes
authors: J
authors: van Loon
authors: Dirk E M
authors: DE
authors: Van Raemdonck
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001926:Brain Death / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000032:analysis; D006439:Hemodynamics; D008168:Lung / Q000473:pathology*; D055370:Lung Injury / Q000209:etiology* / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011180:Postmortem Changes; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018925:Chemokines