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  • Title: Identification and description of a novel murine model for polytrauma and shock.
    Author: Gentile LF, Nacionales DC, Cuenca AG, Armbruster M, Ungaro RF, Abouhamze AS, Lopez C, Baker HV, Moore FA, Ang DN, Efron PA.
    Journal: Crit Care Med; 2013 Apr; 41(4):1075-85. PubMed ID: 23399937.
    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. DESIGN: Pre-clinical controlled in vivo laboratory study. SETTING: Laboratory of Inflammation Biology and Surgical Science. SUBJECTS: Six- to 10-week-old C57BL/6 (B6) mice. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.
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