Impact of Hypobaria and Hypoxia Exposure on Mortality, Inflammation, and Coagulopathy in an Animal Model of Polytrauma

Abstract Introduction Following traumatic injury, both the inflammatory and hemostatic systems are activated. Patients experience a systemic increase in circulating cytokines and coagulation leading to a greater risk of organ dysfunction. Post-trauma aeromedical evacuation exposes patients to hypobaria and potential hypoxia. We sought to assess the impact of hypobaria and hypoxic (H/H) on mortality, coagulation, and inflammation in a mouse model of polytrauma. Materials and Methods Eight- to 12-week-old male C57BL/6J mice were subjected to sham or polytrauma operation with the latter consisting of bowel ischemia via laparotomy and superior mesenteric artery (SMA) occlusion, gastrocnemius muscle crush, and tibia fracture. Sham mice were subjected to laparotomy only. Immediately post SMA reperfusion, animals were randomized to (1) 6 hours at sea level with normobaria and normoxia (N/N) conditions or (2) simulated aeromedical evacuation with H/H conditions. At 6 hours post SMA reperfusion, mice were subjected to general anesthesia, cardiac puncture blood draw, and bronchioalveolar lavage (BAL). Global coagulation was measured by rotational thromboelastometry (ROTEM), and plasma mediators were measured by enzyme-linked immunosorbent assay (ELISA) and Luminex. Extracellular vesicles (EVs) were isolated for treatment of mouse macrophages and naive mouse blood. Results Compared to sham-operated mice, polytrauma mice under N/N conditions exhibited marked hypothermia (38.86 vs. 29.97 °C), systemic inflammation, and platelet activation as evidenced by an increase in plasma MIP-2, IL-6, and P-selectin, and developed alveolar inflammation with increases in BAL MIP-2 and IL-6 6 hours after traumatic injury. Extracellular vesicles isolated from polytrauma mice stimulated a greater release of both MIP-2 and IL-6 from mouse macrophages compared to EVs from sham mice. Polytrauma mice also demonstrated a decrease in platelets and an increase in maximum clot firmness (MCF) compared to sham. In polytrauma mice, H/H exposure significantly worsened hypothermia (N/N trauma vs. H/H trauma; 28.34 °C vs. 26.32 °C) and increased inflammation with elevated plasma levels of MIP-2 andIL-6, and higher MIP-2 in BAL samples. At higher concentrations, EVs isolated from H/H polytrauma mice stimulated a greater release of both MIP-2 and IL-6 from mouse macrophages compared to N/N polytrauma EVs. However, coagulation appeared to not be affected by the simulated aeromedical evacuation. Platelet count and MCF did not differ between H/H and N/N groups after polytrauma. Finally, polytrauma mice with H/H exposure had an increased mortality rate at 6 hours compared to those at sea level (N/N trauma vs. H/H trauma; 7.69% vs. 31.82%). Conclusions The polytrauma model induces marked circulatory dysfunction, systemic inflammation, thrombocytopenia, and hypercoagulation in mice. Hypobaria and hypoxia exposure further increased mortality, circulatory dysfunction, and inflammation following polytrauma.