低气压和高氧环境对脓毒症生存和能量代谢的影响。

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

机构信息

From the Center for Vaccine Development, (M.C., K.A., A.S.C.) University of Maryland School of Medicine, Baltimore, Maryland, Department of Anesthesiology, and Shock, Trauma, and Anesthesiology Research Center (STAR) (P.T., J.L.P., A.M., P.F.S., G.F.), and Department of Pathology (T.C.), University of Maryland School of Medicine, Baltimore, Maryland.

出版信息

J Trauma Acute Care Surg. 2018 Jul;85(1S Suppl 2):S68-S76. doi: 10.1097/TA.0000000000001909.

DOI:10.1097/TA.0000000000001909

PMID:29953420

Abstract

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 hours 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 hours later, rats were then placed in hypobaric chambers for 6 hours 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 postsurgery.

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 of 30) CLP rats undergoing hypobaria versus 12.5% (3 of 24) of CLP rats exposed to normobaria died (p = 0.715) while 12% (3 of 25) of CLP rats exposed to hyperoxia versus 20.7% (6 of 29) of CLP rats exposed to normoxia died (p = 0.48). The ratio of mitochondrial ATP-generating O2 consumption to resting respiration was higher in the CLP plus hypobaria under 100% compared with 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 postinjury were lower than those at baseline for shams.

CONCLUSION

We conclude that neither "in-flight" hyperoxia nor hypobaria exacerbate sepsis or neurologic injury.

摘要

背景

受伤的作战人员被空运到三级医疗护理机构，他们会受到许多压力，这些压力可能会促进败血症的发展。在这项研究中，我们检验了这样一个假设，即在大鼠腹腔感染发作后 24 小时内暴露于“飞行”低气压和/或高氧环境会加速败血症和幸存者神经损伤的发展和/或严重程度。

方法

Sprague-Dawley 大鼠接受盲肠结扎/穿刺（CLP）或假手术。24 小时后，大鼠被放置在低气压室中 6 小时，并被分配到常压条件下，并维持在 21%或 100%的 O2，或在低气压条件下（相当于 8000 英尺的高度），但维持在 28%或 100%的 O2。CLP 或假手术后两天，采集血液样本以测定细胞因子水平，并从一部分动物的大脑和心脏中分离出线粒体，用于分析线粒体耗氧量。动物还在手术前和 15 天后进行神经运动功能障碍评估。

结果

在研究的 70 只大鼠中，16.7%的 CLP 大鼠死亡，而无一只假手术大鼠死亡。所有的 CLP 大鼠都有腹膜炎的证据，而无一例假手术大鼠有此证据。接受低气压的 CLP 大鼠中有 20%（6 只中的 3 只）死亡，而接受常压的 CLP 大鼠中有 12.5%（24 只中的 3 只）死亡（p=0.715），而接受高氧的 CLP 大鼠中有 12%（25 只中的 3 只）死亡，而接受常氧的 CLP 大鼠中有 20.7%（29 只中的 6 只）死亡（p=0.48）。CLP 加低气压下 100%的线粒体产生 ATP 的 O2 消耗与静息呼吸的比值高于假手术组。仅在常压下接受高氧的 CLP 大鼠的线粒体中观察到 H2O2 生成的差异。损伤后 15 天获得的综合神经评分低于基线时的评分。