title: Development and validation of 4 different rat models of uncontrolled hemorrhage.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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] mm Hg, respectively). One-hour survival was 100% in all 4 models.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Morgan
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Prakash
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Vercammen
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, Ohio3Institute for Military Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Timothy
authors.initials: T
authors.lastname: Pritts
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois4Editor, JAMA Surgery.
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics; D006470:Hemorrhage; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D015996:Survival Rate