A Murine Liver Laceration Model Simplifying Quantification of Trauma-Induced Hemorrhage Coagulopathy, Inflammation,...

Uncontrolled hemorrhage remains a leading cause of preventable death in trauma patients, and trauma-induced coagulopathy (TIC) is a major determinant of early mortality. Experimental models that reliably recapitulate hemorrhage and associated coagulopathic responses are essential for mechanistic studies and evaluation of targeted interventions. Here, we describe a standardized murine model of profound hemorrhage using reproducible liver laceration (LL) causing hemorrhage, which can be quantified precisely, while also tracking simultaneously systemic coagulopathy, inflammatory markers, and mortality. Mice undergo a standardized midline laparotomy followed by LL, and blood loss is quantified by blood-soaked sponges. Systemic markers of coagulation, fibrinolysis, and inflammation markers are collected by retro-orbital blood draw prior to and at pre-specified, serial intervals post-procedure. LL with blood loss reliably produces TIC (characterized by activated partial thromboplastin time (aPTT) prolongation, thrombin-antithrombin (TAT) complex increase, selective depletion of coagulation factors (F) V and VIII with activation of fibrinolysis). In parallel, inflammatory activation is evidenced by increased interleukin-6 (IL-6). Moreover, the model further allows survival analyses after midline incision repair. As a translational application, rhFVIIa and TXA are used to prove that the model is sensitive to bleed rescue with pharmacologic modulation of coagulation and fibrinolytic parameters. Compared to large-animal models, this murine system offers an economical, versatile, and easily scalable opportunity to study innovative, targeted interventions for traumatic hemorrhage.