Wagner Julie, Strosing Karl M, Spassov Sashko G, Lin Ziwei, Engelstaedter Helen, Tacke Sabine, Hoetzel Alexander, Faller Simone
Department of Anesthesiology and Critical Care Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Veterinary Clinical Sciences, Clinic for Small Animal-Surgery, Justus-Liebig-University Giessen, Giessen, Germany.
PLoS One. 2018 Feb 22;13(2):e0192896. doi: 10.1371/journal.pone.0192896. eCollection 2018.
Mechanical ventilation is a life-saving clinical treatment but it can induce or aggravate lung injury. New therapeutic strategies, aimed at reducing the negative effects of mechanical ventilation such as excessive production of reactive oxygen species, release of pro-inflammatory cytokines, and transmigration as well as activation of neutrophil cells, are needed to improve the clinical outcome of ventilated patients. Though the inhaled anesthetic sevoflurane is known to exert organ-protective effects, little is known about the potential of sevoflurane therapy in ventilator-induced lung injury. This study focused on the effects of delayed sevoflurane application in mechanically ventilated C57BL/6N mice. Lung function, lung injury, oxidative stress, and inflammatory parameters were analyzed and compared between non-ventilated and ventilated groups with or without sevoflurane anesthesia. Mechanical ventilation led to a substantial induction of lung injury, reactive oxygen species production, pro-inflammatory cytokine release, and neutrophil influx. In contrast, sevoflurane posttreatment time dependently reduced histological signs of lung injury. Most interestingly, increased production of reactive oxygen species was clearly inhibited in all sevoflurane posttreatment groups. Likewise, the release of the pro-inflammatory cytokines interleukin-1β and MIP-1β and neutrophil transmigration were completely prevented by sevoflurane independent of the onset of sevoflurane administration. In conclusion, sevoflurane posttreatment time dependently limits lung injury, and oxidative and pro-inflammatory responses are clearly prevented by sevoflurane irrespective of the onset of posttreatment. These findings underline the therapeutic potential of sevoflurane treatment in ventilator-induced lung injury.
机械通气是一种挽救生命的临床治疗方法，但它可诱发或加重肺损伤。需要新的治疗策略来减少机械通气的负面影响，如活性氧过度产生、促炎细胞因子释放、中性粒细胞的迁移和激活，以改善机械通气患者的临床结局。尽管已知吸入麻醉药七氟烷具有器官保护作用，但关于七氟烷治疗呼吸机诱导性肺损伤的潜力却知之甚少。本研究聚焦于延迟应用七氟烷对机械通气的C57BL/6N小鼠的影响。分析并比较了未通气组、通气组以及通气且接受或未接受七氟烷麻醉组的肺功能、肺损伤、氧化应激和炎症参数。机械通气导致肺损伤、活性氧产生、促炎细胞因子释放和中性粒细胞浸润显著增加。相比之下，七氟烷后处理可使肺损伤的组织学特征呈时间依赖性减轻。最有趣的是，所有七氟烷后处理组中活性氧的产生增加均明显受到抑制。同样，七氟烷可完全抑制促炎细胞因子白细胞介素-1β和巨噬细胞炎性蛋白-1β的释放以及中性粒细胞迁移，且与七氟烷给药时间无关。总之，七氟烷后处理可使肺损伤呈时间依赖性减轻，且无论后处理何时开始，七氟烷均可明显抑制氧化和促炎反应。这些发现凸显了七氟烷治疗呼吸机诱导性肺损伤的治疗潜力。
