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

实验性急性呼吸窘迫综合征自主呼吸所致肺损伤的分布及机制：保护性机械通气改善的综合研究

• 批准号: 158129290
• 负责人: Professor Dr. Marcelo Gama de Abreu
• 金额: --
• 依托单位: Klinik und Poliklinik für Anästhesiologie und Intensivtherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/158129290?language=en
• 关键词: Distribution; mechanisms; lung; injury; induced

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.

急性呼吸窘迫综合征（ARDS）患者机械通气期间的自发呼吸会影响肺损伤。在以前的项目中，我们表明，在中等的ARDS中，自发呼吸减轻了肺部的全球压力和应变，有助于改善气体交换并减少肺部损伤。相比之下，其他人也观察到，在严重的ARDS中，已经提出自发呼吸会使肺功能和损害恶化，但是这种作用的机制只能理解不足。在这个延续项目中，我们旨在调查应力与晶体与时间产物和斜率如何调节肺泡上皮细胞中两次介导蛋白和炎症介质的机械敏感反应。同样，我们将研究自发呼吸对胸膜内压力和炎症区域分布的影响，在末端爆炸时具有稳定且不稳定的肺单位的实验模型中。我们假设，在严重的ARDS机械通气期间，自发呼吸对肺功能和损伤的影响取决于应力和应变与肺泡上皮细胞的时间产物和斜率，以及在末端呼吸时的肺单位的稳定性。这项调查可能有助于改善ARDS中的肺部保护通气策略。