title: An Evolving Uncontrolled Hemorrhage Model Using Cynomolgus Macaques.
abstract: BACKGROUND
  Trauma-induced hemorrhagic shock produces hemodynamic changes that often result in a systemic inflammatory response that can lead to multiple organ failure and death. In this prospective study, the pathophysiology of a nonhuman primate uncontrolled hemorrhagic shock model is evaluated with the goal of creating an acute systemic inflammatory syndrome response and a reproducible hemorrhage.
  
  
  METHODS
  Nonhuman primates were divided into 2 groups. A laparoscopic left hepatectomy was performed in groups A and B, 60% and 80%, respectively, resulting in uncontrolled hemorrhage. Resuscitation during the prehospital phase lasted 120 min and included a 0.9% saline bolus at 20 mL/kg. The hospital phase involved active warming, laparotomy, hepatorrhaphy for hemostasis, and transfusion of packed red blood cells (10 mL/kg). The animals were recovered and observed over a 14-day survival period with subsequent necropsy for histopathology.
  
  
  RESULTS
  Baseline demographics and clinical parameters of the two groups were similar. Group A (n = 7) underwent a 57.7% ± 2.4% left hepatectomy with a 33.9% ± 4.0% blood loss and 57% survival. Group B (n = 4) underwent an 80.0% ± 6.0% left hepatectomy with 56.0% ± 3.2% blood loss and 75% survival. Group B had significantly lower hematocrit (P < 0.05) for all postinjury time points. Group A had significantly elevated creatinine on postoperative day 1. Nonsurvivors succumbed to an early death, averaging 36 h from the injury. Histopathologic evaluation of nonsurvivors demonstrated kidney tubular degeneration.
  
  
  CONCLUSIONS
  Nonhuman primates displayed the expected physiologic response to hemorrhagic shock due to liver trauma as well as systemic inflammatory response syndrome with resultant multiple organ dysfunction syndrome and either early death or subsequent recovery. Our next step is to establish a clinically applicable nonhuman primate polytrauma model, which reproduces the prolonged maladaptive immunologic reactivity and end-organ dysfunction consistent with multiple organ failure found in the critically injured patient.
authors.affiliation: *Department of Surgery, Walter Reed National Military Medical Center, Bethesda; and †Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring; ‡Department of Surgery, Uniformed Services, University of the Health Sciences, Bethesda, Maryland.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Bograd
authors.forename: Jason S
authors.initials: JS
authors.lastname: Radowsky
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vicente
authors.forename: Earl H
authors.initials: EH
authors.lastname: Lee
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.forename: Eric A
authors.initials: EA
authors.lastname: Elster
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000503:physiopathology* / Q000628:therapy*; D006498:Hepatectomy; D007249:Inflammation; D010535:Laparoscopy; D008099:Liver / Q000473:pathology / Q000601:surgery; D008252:Macaca fascicularis; D008297:Male; D011446:Prospective Studies; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*