Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format

S. David Cho, John B. Holcomb, Brandon H. Tieu, Michael S. Englehart, Melanie S. Morris, Z. Ayhan Karahan, Samantha A. Underwood, Patrick J. Muller, M. Dale Prince, Leticia Medina, Jill Sondeen, Christian Shults, Michael Duggan, Malek Tabbara, Hasan B. Alam, Martin A. Schreiber

Research output: Contribution to journalArticle

45 Scopus citations

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°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 overtime (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.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalShock
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Coagulopathy
  • Femur fracture
  • Multicenter
  • Preclinical trial
  • Resuscitation
  • Shock
  • Swine
  • Trauma

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format'. Together they form a unique fingerprint.

  • Cite this

    Cho, S. D., Holcomb, J. B., Tieu, B. H., Englehart, M. S., Morris, M. S., Karahan, Z. A., Underwood, S. A., Muller, P. J., Prince, M. D., Medina, L., Sondeen, J., Shults, C., Duggan, M., Tabbara, M., Alam, H. B., & Schreiber, M. A. (2009). Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format. Shock, 31(1), 87-96. https://doi.org/10.1097/SHK.0b013e3181777ffb