Available online 15 September 2022

ABSTRACTINTRODUCTION

Traumatic brain injuries (TBI) represent a significant percentage of critical injuries in military conflicts. Following injury, wounded warfighters are often subjected to multiple aeromedical evacuations (AE) and associated hypobaria, yet the impact in TBI patients remains to be characterized. This study evaluated the impact of two consecutive simulated AEs in a fluid-percussion TBI model in swine to characterize these effects.

METHODS

Following instrumentation, anesthetized Yorkshire swine underwent a frontal TBI via fluid-percussion. A hypobaric chamber was then used to simulate AE at simulated cabin pressure equivalent to 8000ft (hypobaria) in a 6 hour initial flight on day 3, followed by a 9 hour flight on day 6, and were monitored for 14 days. Animals in the normobaria group were subjected to the same steps at sea level while Sham animals in both groups were instrumented but not injured. Parameters measured included physiologic response, intracranial pressure (ICP), hematology, chemistry, and serum cytokines. Histopathology of brain, lung, intestine, and kidney was performed, as well as fluorojade staining to evaluate neurodegeneration. All animals were divided into sub-groups by block randomization utilizing a 2-way ANOVA to analyze independent variables.

RESULTS

Survival was 100% in all groups. Physiologic parameters were largely similar across groups as well during both 6 and 9 hour AE. Animals exposed to hypobaria in both the TBI and Sham groups had elevated heart rate (HR) during the 6 hour flight (p<0.05). Three animals in the TBI hypo group demonstrated leukocytosis with histologic evidence of meningeal inflammatory response. Expression of serum cytokines was low across all groups. No significant neuronal degeneration was identified in areas away from the site of injury.

CONCLUSION

Aeromedical evacuation in swine was not associated with significant differences in physiologic measures, cytokine expression or levels of neuronal degeneration. Histological examination revealed higher risk of meningeal inflammatory response and leucocytosis in swine exposed to hypobaria.

Section snippetsINTRODUCTION

Traumatic brain injury (TBI) accounts for up to 60% of modern warfare injuries[1], [2], [3], [4], [5], and represents a significant percentage of potentially survivable critical injuries sustained by service members[6]. Current military evacuation practice utilizes Critical Care Air Transport Teams (CCATT) during conflicts to evacuate combat casualties rapidly and effectively to higher levels of care[3], [7], [8], [9], [10]. Traditionally, this rapid transport to higher level of care via

MATERIAL AND METHODS

The study protocol was reviewed and approved by the Institutional Animal Care and Use Committee in compliance with all applicable Federal regulations governing the protection of animals in research. These experiments reported herein were conducted in compliance with the Animal Welfare Act and per the principles set forth in the “Guide for Care and Use of Laboratory Animals,” Institute of Laboratory Animals Resources, National Research Council, National Academy Press, 2011.

Twenty-four male

Instrumentation and TBI

Survival was 100% in all groups for the entirety of the 14-day experimental period. The average weight of the study animals was 33.3 ± 3.6 kg (mean ± standard deviation) with no significant variation between groups.

During the instrumentation period on Day 1, animals assigned to the TBI groups were noted to have a higher baseline MAP compared to the animals in the Sham groups during the first 150 minutes of the experiment (p < 0.05) (Fig. 2A). In the TBI groups, the forehead fluid-percussion

DISCUSSION

The purpose of this study was to evaluate the effects of two consecutive long haul aeromedical evacuations in the setting of traumatic brain injury in swine. Other studies suggested that alterations in physiologic and biochemical parameters have a deleterious effect on the test subjects, however, this has not been evaluated in a large animal TBI model in a realistic military casualty evacuation scenario[18], [24], [25], [26].

During development of this experiment, we sought to decrease the

Author Contributions

The following authors contributed to this manuscript in the following manner: Anke Scultetus (secured funding, study design, data collection, data analysis and interpretation, manuscript editing), Francoise Arnaud (study design, experimental procedure, data collection, data analysis, data interpretation, writing manuscript), Ashraful Haque (Experimental procedures, data collection and analysis), Jordan Hubbell (Experimental procedures, data collection and analysis), Natalie Coschigano

Declaration of Competing Interest

None of the authors have any commercial associations that might create a conflict of interest nor do any of the authors have any financial interests or personal relationships with other people or organizations that would represent a conflict of interest.

ACKNOWLEDGEMENTS

The authors thank Dr. Richard McCarron for his help in acquiring funding for this study. Noemy Carballo and Andrea White for assistance with animal procedures, Drs. Ye Chen, Ming Gu, and Mr. Mike Hammett for laboratory assistance.

Funding

This work was supported/funded by the United States Air Force, 59th HPW, work unit number 6115HP.2380.001.A1304.

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