Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Anesthesiology. 2011 Sep;115(3):474-82. doi: 10.1097/ALN.0b013e318229a640.
The interaction between neutrophils and activated endothelium is essential for the development of multiple organ dysfunction in patients with hemorrhagic shock (HS). Mechanical ventilation frequently is used in patients with HS. The authors sought to investigate the consequences of mechanical ventilation of mice subjected to HS on microvascular endothelial activation in the lung and kidney.
Anesthetized wild type C57BL/6 male mice were subjected to controlled hemorrhage; subgroups of mice were mechanically ventilated during the HS insult. To study the effect of acute hypoxia on the mice, the animals were housed in hypoxic cages. Gene expression levels was assessed by quantitative real-time polymerase chain reaction. Protein expression was assessed by immunohistochemistry and enzyme-linked immunosorbent assay.
Ninety minutes after the shock induction, a vascular bed-specific, heterogeneous proinflammatory endothelial activation represented by E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 expression was seen in kidney and lung. No differences in adhesion molecules between the spontaneously breathing and mechanically ventilated mice were found. Concentrations of the proinflammatory cytokines chemokine (C-X-C motif) ligand 1 (11.0-fold) and interleukin-6 (21.7-fold) were increased after 90 min of HS. Two hours of 6% oxygen did not induce the expression of E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 in the kidneys and the lung.
Hemorrhagic shock leads to an early and reversible proinflammatory endothelial activation in kidney and lung. HS-induced endothelial activation is not changed by mechanical ventilation during the shock phase. Hypoxia alone does not lead to endothelial activation. The observed proinflammatory endothelial activation is mostly ischemia- or reperfusion-dependent and not related to hypoxia.
中性粒细胞与激活的内皮细胞之间的相互作用对于失血性休克（HS）患者多器官功能障碍的发展至关重要。机械通气经常用于 HS 患者。作者试图研究 HS 小鼠机械通气对肺和肾微血管内皮激活的影响。
麻醉的野生型 C57BL/6 雄性小鼠接受控制性出血；亚组小鼠在 HS 损伤期间接受机械通气。为了研究急性缺氧对小鼠的影响，将动物置于缺氧笼中。通过定量实时聚合酶链反应评估基因表达水平。通过免疫组织化学和酶联免疫吸附试验评估蛋白表达。
在休克诱导 90 分钟后，在肾脏和肺部观察到血管床特异性、不均匀的促炎内皮激活，表现为 E-选择素、血管细胞黏附分子 1 和细胞间黏附分子 1 的表达。在自主呼吸和机械通气的小鼠之间，黏附分子没有差异。趋化因子（C-X-C 基序）配体 1（11.0 倍）和白细胞介素-6（21.7 倍）的促炎细胞因子浓度在 HS 90 分钟后增加。2 小时 6%氧气不会诱导肾脏和肺部 E-选择素、血管细胞黏附分子 1 和细胞间黏附分子 1 的表达。
失血性休克导致肾脏和肺部早期和可逆的促炎内皮激活。HS 诱导的内皮激活在休克阶段不受机械通气的影响。单独缺氧不会导致内皮激活。观察到的促炎内皮激活主要与缺血再灌注有关，与缺氧无关。
