Distribution and mechanisms of lung injury induced by spontaneous breathing in experimental acute respiratory distress syndrome: A comprehensive investigation towards improvement of protective mechanical ventilation

急性呼吸窘迫综合征（ARDS）患者机械通气时的自主呼吸可影响肺损伤。在之前的一个项目中，我们发现在中度ARDS中，自发呼吸减少了肺部的整体压力和应变，有助于改善气体交换，减少肺损伤。相比之下，其他人和我们观察到，在严重的ARDS中，自发呼吸被认为会加重肺功能和损伤，但这种影响的机制尚不清楚。在这个后续项目中，我们的目标是研究应力-应变、时间产物和斜率如何调节肺泡上皮细胞中双调节蛋白和炎症介质的机械敏感反应。此外，我们将研究自主呼吸对严重急性呼吸窘迫综合征（ARDS）终末稳定和不稳定肺单元的实验模型胸膜内压力和炎症区域分布的影响。我们假设，在重型ARDS机械通气期间，自主呼吸对肺功能和损伤的影响是由肺泡上皮细胞的应力-应变与时间乘积和斜率以及肺脏单位在终末呼气时的稳定性决定的。本研究可能有助于改进ARDS患者的肺保护性通气策略。

Spontaneous breathing during mechanical ventilation in patients with the acute respiratory distress syndrome (ARDS) can affect lung injury. In a previous project, we showed that in moderate ARDS, spontaneous breathing decreases global stress and strain in the lungs, contributing to improve gas exchange and reduce lung injury. In contrast, others and we observed that in severe ARDS, spontaneous breathing has been suggested to worsen lung function and damage, but the mechanisms underlying such effects are only poorly understood. In this continuation project, we aim at investigating how stress-and-strain vs. time product and slope modulate the mechano-sensitive response of amphiregulin and inflammatory mediators in alveolar epithelial cells. Also, we shall investigate the effects of spontaneous breathing on intrapleural pressure and regional distribution of inflammation in an experimental model of severe ARDS with stable and unstable lung units at end-expiration. We hypothesize that, during mechanical ventilation in severe ARDS, the effects of spontaneous breathing on lung function and injury are determined by the stress-and-strain vs. time product and slope of alveolar epithelial cells, as well as the stability of lung units at end-expiration. This investigation may contribute to the improvement of lung protective ventilation strategies in ARDS.