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，自主呼吸减少了肺部的整体压力和应变，有助于改善气体交换和减少肺损伤。相反，我们和其他人观察到，在严重的ARDS中，自主呼吸被认为会使肺功能和损伤恶化，但这种影响的机制却知之甚少。在这个延续的项目中，我们的目的是调查如何应力和应变与时间的产品和斜率调节肺泡上皮细胞的双调蛋白和炎症介质的机械敏感性反应。此外，我们还将在一个呼气末肺单位稳定和不稳定的严重ARDS实验模型中研究自主呼吸对胸膜内压和炎症区域分布的影响。我们假设，在严重ARDS的机械通气过程中，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的乘积和斜率以及呼气末肺单位的稳定性决定的。本研究有助于完善ARDS患者的肺保护性通气策略。