Robley Rex Veterans Affairs Medical Center , Louisville, Kentucky.
Department of Surgery, University of Louisville , Louisville, Kentucky.
Am J Physiol Lung Cell Mol Physiol. 2018 Sep 1;315(3):L339-L347. doi: 10.1152/ajplung.00183.2017. Epub 2018 May 3.
Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is intravenous blood and fluids. CR restores central hemodynamics, but vital organ flow can drop, causing hypoperfusion, hypoxia, damage-associated molecular patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus direct peritoneal resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male Sprague-Dawley rats were randomized to groups ( n = 8/group) in one of two sets: 1) sham (no HS, CR, or DPR), 2) HS/CR (HS = 40% mean arterial pressure (MAP) for 60 min, CR = shed blood + 2 volumes normal saline), or 3) HS/CR + DPR. The first set underwent whole lung blood flow by colorimetric microspheres. The second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung, including cytokines, hyaluronic acid (HA), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 protein (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). Statistics were by ANOVA and Tukey-Kramer test with a priori P < 0.05. HS/CR increased serum LPS, HA, HMGB1, and some cytokines [interleukin (IL)-1α, IL-1β, IL-6, and interferon-γ]. Lung TLR4 and MYD88 were increased but not TRIF compared with Shams. HS/CR + DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared with HS/CR. The data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity and mortality by downregulating the systemic DAMP response.
传统的失血性休克（HS）复苏（CR）是静脉输血和补液，这是创伤性死亡率的主要原因。CR 恢复了中心血流动力学，但重要器官的血流可能会下降，导致灌注不足、缺氧、损伤相关分子模式（DAMPs）和远隔器官功能障碍（即肺）。CR 加直接腹膜复苏（DPR）可预防肠和肝灌注不足。我们假设 DPR 通过改变 DAMPs 来预防 HS/CR 中的肺损伤。麻醉雄性 Sprague-Dawley 大鼠随机分为两组（每组 8 只）：1）假手术（无 HS、CR 或 DPR），2）HS/CR（HS=40%平均动脉压（MAP）持续 60 分钟，CR=失血+2 倍生理盐水），或 3）HS/CR+DPR。第一组通过比色微球进行全肺血流测量。第二组进行组织采集，用于 Luminex、ELISA 和组织病理学检查。血清和/或肺中测量脂多糖（LPS）和 DAMPs，包括细胞因子、透明质酸（HA）、高迁移率族蛋白 B1（HMGB1）、Toll 样受体 4（TLR4）、髓样分化初级反应 88 蛋白（MYD88）和 TIR 结构域包含衔接诱导干扰素-β（TRIF）。统计学分析采用方差分析和 Tukey-Kramer 检验，事先 P<0.05。HS/CR 增加了血清 LPS、HA、HMGB1 和一些细胞因子[白细胞介素（IL）-1α、IL-1β、IL-6 和干扰素-γ]。与 Sham 相比，肺 TLR4 和 MYD88 增加，但 TRIF 没有增加。与 HS/CR 相比，HS/CR+DPR 降低了 LPS、HA、细胞因子、HMGB1、TLR4 和 MYD88 水平，但没有改变 TRIF。数据表明，肠道来源的 DAMPs 可以通过辅助 DPR 来调节，以防止肺 TLR-4 介导的过程激活。此外，DPR 还改善了肺血流并减少了肺组织损伤。HS/CR 中的辅助 DPR 通过下调全身 DAMP 反应，有可能改善发病率和死亡率。
