Identification and Description of a Novel Murine Model for Polytrauma and Shock

• Published in: Critical care medicine Vol. 41; no. 4; pp. 1075 - 1085
• Main Authors: Gentile, Lori F, Nacionales, Dina C, Cuenca, Alex G, Armbruster, Michael, Ungaro, Ricardo F, Abouhamze, Amer S, Lopez, Cecelia, Baker, Henry V, Moore, Frederick A, Ang, Darwin N, Efron, Philip A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 01-04-2013; Lippincott Williams & Wilkins
• Subjects: Acute Kidney Injury - immunology; Acute Kidney Injury - pathology; Animals; Biological and medical sciences; Brain Injuries - immunology; Brain Injuries - pathology; CD4-Positive T-Lymphocytes; Cytokines - blood; Disease Models, Animal; Fractures, Bone - immunology; Fractures, Bone - pathology; Liver Diseases - immunology; Liver Diseases - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Multiple trauma; Multiple Trauma - immunology; Multiple Trauma - pathology; Shock, Hemorrhagic - immunology; Shock, Hemorrhagic - pathology; Spleen - pathology; Traumas. Diseases due to physical agents; Shock; Femur; Diseases of the osteoarticular system; Rodentia; Fracture; Identification; Inflammation; Gene expression; Hemorrhage; Trauma; Vertebrata; Immunosuppression; Mammalia; Mouse; Animal; Models; immune suppression; Multiple injury; femur fracture
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/CCM.0b013e318275d1f9

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 (Ly6GCD11b 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.