Does Increased Non-Linear Behavior Caused by Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?

急性肺损伤（ALI）是由各种不同的损伤引起的，无论是直接对肺还是对身体的其他部位。大约50%的患者死亡。ALI的特征在于通常将血液与空气间隔开的屏障的泄漏增加。因此充满空气空间的流体不仅使患者难以充分获得氧气，而且通过改变肺内的表面力而显著增加呼吸功。因此，患者必须进行机械通气。然而，使用正压使肺膨胀的行为通常会通过塌陷组织的反复打开和闭合或通过其过度扩张而造成进一步的损伤。据估计，呼吸机诱导的肺损伤（VILI）本身导致约30%的死亡率。最大限度减少VILI的最佳方法是通过使用小的程控呼吸，以便不过度充气肺，同时仍然允许足够的气体交换，叠加在背景压力上，以便预充气肺并防止它们反复塌陷。一个遗留的问题是，就像橡皮筋在拉伸时改变其弹性一样，肺在扩张时也会改变其机械特性。此外，肺要复杂得多，因为不同的区域具有不同的弹性，随着空气流入和流出，弹性会发生不同的变化。气流反过来又取决于区域差异的位置，大小和数量的传导气道。事实上，我们最近首次表明，尽管使用安全的通气方式，肺力学的动态变化可能有助于患者的VILI。本申请提出在动物模型中检查肺力学的动态变化对VILI的贡献程度，作为旨在改善死亡率的更昂贵的大规模临床试验的前奏。

Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.