Abstract
Severe injury and shock remain major sources of morbidity and mortality worldwide. Immunologic dysregulation following trauma contributes to these poor outcomes. Few, if any, therapeutic interventions have benefited these patients, and this is due to our limited understanding of the host response to injury and shock. The Food and Drug Administration requires preclinical animal studies prior to any interventional trials in humans; thus, animal models of injury and shock will remain the mainstay for trauma research. However, adequate animal models that reflect the severe response to trauma in both the acute and subacute phases have been limited. Here we describe a novel murine model of polytrauma and shock that combines hemorrhagic shock, cecectomy, long bone fracture, and soft-tissue damage. This model produces an equivalent Injury Severity Score associated with adverse outcomes in humans, and may better recapitulate the human leukocyte, cytokine, transcriptomic, and overall inflammatory response following injury and hemorrhagic shock.