LAUSR

BACKGROUND Aeromedical evacuation can expose traumatically injured patients to low pressure (hypobaria) and hypoxia. Here we sought to assess the impact of hypobaria on inflammation, organ injury, and mortality in a mouse model of polytrauma. METHODS Eight to 12 week-old male C57BL/6J mice were subjected to sham or polytrauma consisting of bowel ischemia by superior mesenteric artery (SMA) occlusion, hindlimb muscle crush, and tibia fracture. Two hours after injury, animals were randomized to undergo either 6 hours of hypobaria or sea-level, room air conditions. At 8 or 24 hours after injury, transthoracic echocardiography was performed. Acute kidney injury (AKI) biomarkers were measured by qRT-PCR. Plasma cytokine and endothelial injury markers were determined by ELISA. RESULTS Eight hours after traumatic injury, mice exhibited a marked increase in plasma IL-6 (57 vs. 1216 pg/ml), AKI with increased Ngal and Kim-1, and endothelial injury as evidenced by significantly increased plasma hyaluronic acid (96 vs.199 ng/ml), thrombomodulin (23.2 vs. 58.9 ng/ml), syndecan-1 (0.99 vs. 4.34 ng/ml), and E-selectin (38.6 vs. 62.7 ng/ml). The trauma mice also developed cardiac dysfunction with decreased cardiac output and stroke volume at 8 hours post-injury. Hypobaric exposure after polytrauma led to decreased ejection fraction (81.0 vs. 74.2%, p < 0.01) and increased plasma hyaluronic acid (199 vs. 260 ng/ml, p < 0.05), thrombomodulin (58.9 vs. 75.4 ng/ml, p < 0.05), and syndecan-1 (4.34 vs. 8.33 ng/ml, p < 0.001) at 8 hours post-injury. CONCLUSIONS Hypobaria exposure appeared to worsen cardiac dysfunction and endothelial injury following polytrauma and thus may represent a physiological "second hit" following traumatic injury.