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Expression of High Mobility Group Box 1 Protein
in a Polytrauma Model During Ground Transport and
Simulated High-Altitude Evacuation
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Jae Hyek Choi, PhD, DVSc ; Teryn R. Roberts, PhD ; Kyle Sieck, BS ;
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George T. Harea, BS ; Vitali Karaliou, MD ; Daniel S. Wendorff, BS ; Brendan M. Beely, RRT, BS ;
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Leopoldo C. Cancio, MD ; Valerie G. Sams, MD ; Andriy I. Batchinsky, MD 10
ABSTRACT
Background: We investigated the expression of high mobility capabilities carried out via drones are being developed. New
group box 1 (HMGB1) protein in a combat-relevant poly- critical care capabilities and diagnostic tools to help guide tri-
trauma/acute respiratory distress syndrome (ARDS) model. We age and management of casualties will need to be validated to
hypothesized that systemic HMGB1 expression is increased af- avoid increased mortality on future battlefields.
ter injury and during aeromedical evacuation (AE) at altitude.
Methods: Female Yorkshire swine (n =15) were anesthetized Among the injury mechanisms that are likely to cause increased
and cannulated with a 23Fr dual-lumen catheter. Venovenous mortality in future conflicts is chest trauma complicated by
extracorporeal life support (VV ECLS) was initiated via the ARDS. Data from the USAISR Joint Theater Trauma Reg-
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right jugular vein and carried out with animals uninjured on istry from 2003-2011 during Operations Enduring Freedom
day 1 and injured by bilateral pulmonary contusion on day and Iraqi Freedom (OEF/OIF) showed that among the 6,030
2. On both days, animals underwent transport and simulated thoracic injuries, pneumothorax and pulmonary contusions
AE. Systemic HMGB1 expression was measured in plasma were the most common (51.8% and 50.2%, respectively).
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by ELISA. Plasma-free Hb (pfHb) was measured with the use Pulmonary contusion (PC) is one of the common consequences
of spectrophotometric methods. Results: Plasma HMGB1 on of thoracic trauma and may lead to early-onset ARDS. 5,7,8 PC
day 1 was transiently higher at arrival to the AE chambers, is an independent risk factor for pneumonia and ARDS and
increased significantly after injury, reaching highest values at carries a 10%–25% mortality, as well as the possibility of sig-
8,000 ft on day 2, after which levels decreased but remained nificant long-term disability. 9,10
elevated versus baseline at each time point. pfHb decreased on
day 1 at 30,000 ft and significantly increased on day 2 at 8,000 Diagnosis of injury severity following PC and during early
ft and postflight. Conclusions: Systemic HMGB1 demonstrated ARDS is a challenging task especially for combat medics and
sustained elevation after trauma and altitude transport and may Special Operations Forces (SOF). To ease diagnosis of injury se-
provide a useful monitoring capability during en route care. verity for SOF, a novel metric, HMGB1 protein, has been identi-
fied as a mediator of ARDS and is expressed in blood following
Keywords: acute respiratory distress syndrome; polytrauma; activation of damaged cells after chest trauma or smoke inhala-
evacuation; altitude physiology; HMGB1 tion injury. 11–13 In this study, we investigate HMGB1 expression
in systemic blood samples obtained from uninjured and injured
animals that undergo ECLS and AE as part of a larger combat
relevant study. This is the first report of HMGB1 analysis from
Introduction
a severely injured animal model, which mimics human combat
Ground and high-altitude evacuation of combat casualties is injuries and subsequent AE with extracorporeal life support
at the forefront of military research as it presents therapeu- (ECLS). This marker may enable the SOF medic to grade injury
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tic and logistical challenges. Future anti-access area denial severity and prognosis of possible multiorgan failure (MOF) at
operations will prohibit immediate evacuation of casualties or near the point of injury or while in transit during evacuation.
because of contested airspace. This delay in evacuation, ne- This first report aims to inform future efforts toward mobile
cessitating extended care-in-place for combat casualties may laboratory capability, potentially down to a “lab-on-a-chip” for
last from hours to days and mandate changes in practice, far-forward use by SOF. We aim to eventually provide the SOF
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to include prolonged field care (PFC) of casualties. Deliv- medic with this vital tool to monitor injury severity and inflam-
ery of medical supplies to PFC environments and evacuation matory reaction of patients during PFC scenarios.
*Correspondence to Jae Hyek Choi, PhD, DVSc, The Geneva Foundation, 2509 Kennedy Circle, Building 125, San Antonio, TX 78235 or
jae-hyek.choi.ctr@mail.mil
1 Dr Choi is affiliated with the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Insti-
tute of Surgical Research, JBSA Ft. Sam Houston, TX. Dr Roberts is affiliated with the Autonomous Reanimation and Evacuation Program,
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The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX. Mr Sieck is affiliated with
The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX. Mr Harea is affiliated with the
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Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA. Dr Karaliou is affiliated with University of Texas
Health Science Center at San Antonio, Department of Surgery, San Antonio, TX. Mr Wendorff is affiliated with the Autonomous Reanimation
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and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX. Mr
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Beely is affiliated with the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute
of Surgical Research, JBSA Ft. Sam Houston, TX. COL (Ret) Cancio is affiliated with US Army Institute of Surgical Research, JBSA Ft. Sam
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Houston, TX. Lt Col Sams is affiliated with San Antonio Military Medical Center, JBSA Ft. Sam Houston, TX. Dr Batchinsky is affiliated with
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the Autonomous Reanimation and Evacuation Program, The Geneva Foundation, Tacoma, WA; and US Army Institute of Surgical Research,
JBSA Ft. Sam Houston, TX
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