Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, 3584 EA, The Netherlands.
Crit Care. 2009;13(6):R182. doi: 10.1186/cc8168. Epub 2009 Nov 16.
Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.
Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH2O positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC).
Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.
Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.
临床研究的结果为白细胞-内皮细胞相互作用在肺部疾病（如急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS））以及全身性疾病（如败血症和多器官衰竭（MOF））的发病机制中的重要性提供了证据。本研究旨在探讨机械通气（MV）引起的肺泡膨胀是否会导致健康小鼠的内皮激活和炎症，不仅在肺部，而且在肺部以外的器官。
健康雄性 C3H/HeN 小鼠麻醉、气管切开并机械通气 1、2 或 4 小时。为了研究肺泡伸展在体内的影响，我们应用了一种 MV 策略，即导致肺组织过度伸展，即 20cmH2O 峰吸气压（PIP）和 0cmH2O 呼气末正压（PEEP）。未通气的假手术动物作为参考组（未通气对照，NVC）。
MV 引起的肺泡膨胀不仅导致肺内新合成的粘附分子，而且在肺以外的器官，如肝脏和肾脏，也导致粘附分子的合成。在大脑中没有观察到激活。此外，我们还证明 MV 后肺、肝和肾组织中的细胞因子和趋化因子表达增加，同时这些器官中的粒细胞募集增加。
我们的数据表明，MV 导致无预先存在的肺损伤的小鼠的内皮激活和炎症，不仅在肺部，而且在远处的器官。
