title: Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format.
abstract: We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. Yorkshire swine were anesthetized, intubated, and instrumented. They then underwent femur fracture, 60% total blood volume hemorrhage, a 30-min shock period, induced hypothermia to 33 degrees C, and hemorrhage volume replacement with 3:1 isotonic sodium chloride solution (NS) at each of three centers. Hemodynamic parameters were measured continuously. Thromboelastography, arterial blood gas, and laboratory values were collected at baseline, after the shock period, and after NS replacement. Thirty-seven animals were used for model development. Eight (21%) died before completion of the study period. Twenty-nine survivors were included in the analysis. MAP (+/-SEM) after the shock period was 32 +/- 2 mmHg and was similar between centers (P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 +/- 0.02, 8.20 +/- 0.65 mmol/L, and 5.29 +/- 0.44 mmol/L, respectively, after NS replacement. These were similar between centers (P > 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy (P < 0.02). Thromboelastography maximum amplitude values were similar among centers (P > 0.05) and demonstrated progressively weakened platelet interaction over time (P < 0.03). Hematocrit was similar after controlled hemorrhage (P = 0.15) and dilution (P = 0.9). The pH, lactate, base deficit, and coagulation tests reflect a severely injured state. A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model.
authors.affiliation: Division of Trauma and Critical Care, Oregon Health and Science University, Portland, Oregon 97239, USA. chos@ohsu.edu
authors.forename: S David
authors.initials: SD
authors.lastname: Cho
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Tieu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Englehart
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Morris
authors.forename: Z Ayhan
authors.initials: ZA
authors.lastname: Karahan
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Underwood
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Muller
authors.forename: M Dale
authors.initials: MD
authors.lastname: Prince
authors.forename: Leticia
authors.initials: L
authors.lastname: Medina
authors.forename: Jill
authors.initials: J
authors.lastname: Sondeen
authors.forename: Christian
authors.initials: C
authors.lastname: Shults
authors.forename: Michael
authors.initials: M
authors.lastname: Duggan
authors.forename: Malek
authors.initials: M
authors.lastname: Tabbara
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
mesh_terms: D000138:Acidosis / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000097:blood / Q000503:physiopathology*; D006400:Hematocrit; D006439:Hemodynamics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D007552:Isotonic Solutions / Q000494:pharmacology; D019344:Lactic Acid / Q000097:blood; D015337:Multicenter Studies as Topic; D015203:Reproducibility of Results; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology*; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D013916:Thrombelastography; D013997:Time Factors; D014857:Warfare
chemical_list: D007552:Isotonic Solutions; D019344:Lactic Acid; D012965:Sodium Chloride