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 (+ or -SEM) after the shock period was 32 + or - 2 mmHg and was similar between centers ( P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 + or - 0.02, 8.20 + or - 0.65 mmol/L, and 5.29 + or - 0.44 mmol/L, respectively, after NS replacement. These were similar between centers ( P greater than 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy ( P less than 0.02). Thromboelastography maximum amplitude values were similar among centers ( P greater than 0.05) and demonstrated progressively weakened platelet interaction over time ( P less than 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2009
- Accession Number
- ADA627464
Entities
People
- Brandon H. Tieu
- John B Holcomb
- Leticia Medina
- M. D. Prince
- Melanie S. Morris
- Michael S. Englehart
- Patrick J. Muller
- S. D. Cho
- Samantha A. Underwood
- Z. A. Karahan
Organizations
- United States Army Institute of Surgical Research