BACKGROUND:Traumatic brain injury (TBI) is common in civilians and military personnel. No potential therapeutics have been evaluated to prevent secondary injury induced by the hypobaric hypoxia (HH) environment integral to postinjury aeromedical evacuation (AE).We examined the role of allopurinol, propranolol, adenosine/lidocaine/magnesium (ALM), or amitriptyline administration prior to simulated flight following murine TBI. METHODS:Mice underwent TBI and were given allopurinol, propranolol, amitriptyline, or ALM prior to simulated AE or normobaric normoxia (NN) control. Heart rate (HR), respiratory rate, and oxygen saturation (SpO 2 ) were recorded throughout simulated AE. Mice were sacrificed at 24 hours, 7 days, or 30 days. Serum and cerebral cytokines were assessed by enzyme-linked immunosorbent assay. Motor function testing was performed with Rotarod ambulation. Immunohistochemistry was conducted to examine phosphorylated tau (p-tau) accumulation in the hippocampus at 30 days. RESULTS:While all treatments improved oxygen saturation, propranolol, amitriptyline, and allopurinol improved AE-induced tachycardia. At 24 hours, both propranolol and amitriptyline reduced tumor necrosis factor alpha levels while allopurinol and ALM reduced tumor necrosis factor alpha levels only in NN mice. Propranolol, amitriptyline, and ALM demonstrated lower serum monocyte chemoattractant protein-1 7 days after AE. Both amitriptyline and allopurinol improved Rotarod times for AE mice while only allopurinol improved Rotarod times for NN mice. Propranolol was able to reduce p-tau accumulation under both HH and NN conditions while ALM only reduced p-tau in hypobaric hypoxic conditions. CONCLUSION:Propranolol lowered post-TBI HR with reduced proinflammatory effects, including p-tau reduction. Amitriptyline-induced lower post-TBI HR and improved functional outcomes without affecting inflammatory response. Allopurinol did not affect vital signs but improved late post-TBI systemic inflammation and functional outcomes. Adenosine/lidocaine/magnesium provided no short-term improvements but reduced p-tau accumulation at 30 days in the HH cohort. Allopurinol may be the best of the four treatments to help prevent short-term functional deficits while propranolol may address long-term effects.
Background Bacterial growth in soft tissue and open fractures is a known risk factor for tissue loss and complications in contaminated musculoskeletal wounds. Current care for battlefield casualties with soft tissue and musculoskeletal wounds includes tactical and strategic aeromedical evacuation (AE). This exposes patients to a hypobaric, hypoxic environment. In the present study, we sought to determine whether exposure to AE alters bacterial growth in contaminated complex musculoskeletal wounds and whether supplemental oxygen had any effect on wound infections during simulated AE. Methods A caprine model of a contaminated complex musculoskeletal wound was employed. Complex musculoskeletal wounds were created and inoculated with bioluminescent Pseudomonas aeruginosa. Goats were divided into three experimental groups: ground control, simulated aeromedical evacuation (AE), and simulated AE with supplemental oxygen (AE+O2). Simulated AE was induced in a hypobaric chamber pressurized to 8800 feet for 7 hours. Bacterial luminescence was measured using a photon counting camera at three timepoints: preflight (20 hours post surgery), postflight (7 hours from preflight and 27 hours post-surgery), and necropsy (24 hours from preflight and 44 hours post surgery). Results There was a significant increase in bacterial growth in the AE group compared to the ground control group measured postflight and at necropsy. Simulated AE induced hypoxia with oxygen saturation less than 93%. Supplemental oxygen corrected the hypoxia and significantly reduced bacterial growth in wounds at necropsy. Conclusions Hypoxia induced during simulated AE enhances bacterial growth in complex musculoskeletal wounds which can be prevented with the application of supplemental oxygen to the host.
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