Development and validation of 4 different rat models of uncontrolled hemorrhage

IMPORTANCE: Hemorrhage is the leading cause of death in military trauma and second leading cause of death in civilian trauma. Although many well-established animal models of hemorrhage exist in the trauma and anticoagulant literature, few focus on directly quantitating blood loss. OBJECTIVE: To establish and validate a reproducible rodent model of uncontrolled hemorrhage to serve as the foundation for developing therapies for noncompressible torso trauma. DESIGN, SETTINGS, AND SUBJECTS: We developed and evaluated 4 different hemorrhage models using male Sprague-Dawley rats (6 rats/model), aged 10 to 14 weeks and weighing 330 to 460 g, at the Department of Surgery, Northwestern University. INTERVENTIONS: We used tail-cut (4 cm), liver punch biopsy (12 mm), liver laceration (3.0 × 1.5 cm), and spleen transection models. All animals underwent invasive hemodynamic monitoring. MAIN OUTCOMES AND MEASURES: Blood loss, expressed as a percentage of total blood volume (TBV), mean arterial pressure, and heart rate, which were recorded at 2- to 5-minute intervals. RESULTS: The tail-cut model resulted in a mean (SD) TBV loss of 15.4%(6.0%) with hemodynamics consistent with class I hemorrhagic shock. The liver punch biopsy model resulted in a mean (SD) TBV loss of 16.7%(3.3%) with hemodynamics consistent with class I hemorrhagic shock. The liver laceration model resulted in a mean (SD) TBV loss of 19.8% (3.0%) with hemodynamics consistent with class II hemorrhagic shock. The spleen transection model resulted in the greatest blood loss (P <.01), with a mean (SD) TBV loss of 27.9%(3.4%) and hemodynamics consistent with class II hemorrhagic shock. The liver laceration and punch biopsy models resulted in most of the blood loss within the first 2 minutes, whereas the spleen transection and tail-cut models resulted in a steady loss during 10 minutes. The liver laceration and spleen transection models resulted in the greatest degree of hemodynamic instability (mean [SD] arterial pressure decreases of 25 [1] and 41 [11]mmHg, respectively). One-hour survival was 100% in all 4 models. CONCLUSIONS AND RELEVANCE: We established and validated the reproducibility of 4 different rat models of uncontrolled hemorrhage. These models provide a foundation to design novel nonsurgical therapies to control hemorrhage, and the different degrees of hemorrhagic shock produced from these models allow for flexibility in experimental design.