Charité-Universitätsmedizin Berlin, Department of Infectious Diseases and Pulmonary Medicine, Charitéplatz 1, D-10117 Berlin, Germany.
Thorax. 2010 Dec;65(12):1077-84. doi: 10.1136/thx.2010.135996. Epub 2010 Oct 22.
Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro and in vivo.
In untreated mice (female C57/Bl6 mice, 11-15 weeks old) and animals treated with adrenomedullin, lung permeability, local and systemic inflammation and markers of distal organ function were assessed following 2 or 6 h of mechanical ventilation with 100% oxygen and protective or moderately injurious ventilator settings, respectively.
Adrenomedullin dramatically reduced lung permeability in VILI in mice, leading to improved oxygenation. Adrenomedullin treatment reduced myosin light chain phosphorylation, attenuated the accumulation of leucocytes in the lung and prevented the increase in lactate and creatinine levels in mice ventilated with high tidal volumes. Moreover, adrenomedullin protected against VILI even when treatment was initiated 2 h after the beginning of mechanical ventilation in a 6 h VILI mouse model.
Adjuvant treatment with adrenomedullin may be a promising new pharmacological approach to attenuate VILI.
机械通气（MV）是急性呼吸衰竭时的一种救命干预措施，没有其他替代方法。然而，即使应用最小机械应激的保护性通气策略也可能引起呼吸机相关性肺损伤（VILI）。除了保护性通气外，还缺乏辅助药理学策略来减轻 VILI。肾上腺髓质素在体外和体内具有稳定血管内皮屏障的特性。
在未治疗的小鼠（雌性 C57/Bl6 小鼠，11-15 周龄）和接受肾上腺髓质素治疗的动物中，在 100%氧气和保护性或中度损伤性通气设置下分别进行 2 或 6 小时机械通气后，评估肺通透性、局部和全身炎症以及远端器官功能标志物。
肾上腺髓质素可显著降低 VILI 小鼠的肺通透性，从而改善氧合。肾上腺髓质素治疗可降低肌球蛋白轻链磷酸化，减少肺白细胞积聚，并防止高潮气量通气小鼠乳酸和肌酐水平升高。此外，即使在 6 小时 VILI 小鼠模型中机械通气开始 2 小时后开始治疗，肾上腺髓质素也能预防 VILI。
辅助治疗用肾上腺髓质素可能是一种有前途的新的药理学方法，可减轻 VILI。
