title: Identification and description of a novel murine model for polytrauma and shock.
abstract: OBJECTIVE
  To develop a novel polytrauma model that better recapitulates the immunologic response of the severely injured patient by combining long-bone fracture, muscle tissue damage, and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically used murine trauma-hemorrhage models.
  
  
  METHODS
  Pre-clinical controlled in vivo laboratory study.
  
  
  METHODS
  Laboratory of Inflammation Biology and Surgical Science.
  
  
  METHODS
  Six- to 10-week-old C57BL/6 (B6) mice.
  
  
  METHODS
  Mice underwent 90 minutes of shock (mean arterial pressure 30 mm Hg) and resuscitation via femoral artery cannulation followed by laparotomy (trauma-hemorrhage), hemorrhage with laparotomy and femur fracture, or laparotomy with cecetomy and femur fracture with muscle tissue damage (polytrauma). Mice were euthanized at 2 hours, 1 day, and 3 days postinjury.
  
  
  RESULTS
  The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing polytrauma exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared with traditional models. Polytrauma was the only model to induce neutrophilia (Ly6G (+)CD11b(+) cells) on days 1 and 3 (p<0.05). Polytrauma, as compared to trauma-hemorrhage and hemorrhage with laparotomy and femur fracture, induced a loss of circulating CD4(+) T cell with simultaneous increased cell activation (CD69(+) and CD25(+)), similar to human trauma. There was a prolonged loss of major histocompatibility complex class II expression on monocytes in the polytrauma model (p<0.05). Results were confirmed by genome-wide expression analysis that revealed a greater magnitude and duration of blood leukocyte gene expression changes in the polytrauma model than the trauma-hemorrhage and sham models.
  
  
  CONCLUSIONS
  This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock.
authors: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors: Lori F
authors: LF
authors: Gentile
authors: Dina C
authors: DC
authors: Nacionales
authors: Alex G
authors: AG
authors: Cuenca
authors: Michael
authors: M
authors: Armbruster
authors: Ricardo F
authors: RF
authors: Ungaro
authors: Amer S
authors: AS
authors: Abouhamze
authors: Cecelia
authors: C
authors: Lopez
authors: Henry V
authors: HV
authors: Baker
authors: Frederick A
authors: FA
authors: Moore
authors: Darwin N
authors: DN
authors: Ang
authors: Philip A
authors: PA
authors: Efron
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001930:Brain Injuries / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000276:immunology* / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009104:Multiple Trauma / Q000276:immunology* / Q000473:pathology; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000473:pathology
chemical_list: D016207:Cytokines
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