Effect of hypobaria and hyperoxia during sepsis on survival and energy metabolism

BACKGROUND Injured warfighters air evacuated to tertiary medical care facilities are subjected to many stresses that may promote the development of sepsis. In this study we tested the hypothesis that exposure to “in-flight” hypobaria and/or hyperoxia within 24 hr after onset of intra-abdominal infection in rats accelerates the development and/or severity of sepsis and neurologic injury in survivors. METHODS Sprague-Dawley rats underwent cecal ligation/puncture (CLP) or sham procedures. Twenty-four hr later, rats were then placed in hypobaric chambers for 6 hrs and assigned to normobaric conditions and maintained at either 21% or 100% O2, or under hypobaric conditions (pressure equivalent to an altitude of 8,000 ft) but maintained under either 28% or 100% O2. Two days after CLP or sham blood samples were obtained for cytokine levels, and mitochondria were isolated from the brain and heart of a subset of animals for analysis of mitochondrial oxygen consumption. Animals were also evaluated for neuromotor impairment before and 15 days post-surgery. RESULTS Among the 70 rats studied 16.7% of CLP but none of the sham-treated rats died. All of the CLP but none of the sham rats had evidence of peritonitis at 2 days. Twenty percent (6/30) CLP rats undergoing hypobaria vs. 12.5% (3/24) of CLP rats exposed to normobaria died (p=0.715) while 12% (3/25) of CLP rats exposed to hyperoxia vs. 20.7% (6/29) of CLP rats exposed to normoxia died (p=0.48). The ratio of mitochondrial ATP-generating O2consumption to resting respiration was higher in the CLP plus hypobaria under 100% compared to shams. The only difference in H2O2 production was observed in mitochondria from CLP rats exposed to hyperoxia under normobaric conditions. Composite neurologic scores obtained 15 days post-injury were lower than those at baseline for shams. CONCLUSION We conclude that neither “in-flight” hyperoxia nor hypobaria exacerbate sepsis or neurologic injury. Address for reprints: Alan S. Cross, MD, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA; email: across@som.umaryland.edu This study was presented at the 2017 annual meeting of the Military Health Sciences Research Symposium, August 27-30, 2017, in Kissimmee, Florida © 2018 Lippincott Williams & Wilkins, Inc.

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