The Effect of Pulmonary Interstitial Edema on Gas Exchange

描述（由申请人提供）：我们的总体目标是了解肺间质水肿（肺泡水肿的前体）影响肺气体交换的机制。肺间质性水肿是健康“干”状态和肺泡泛洪状态之间过渡的一部分。然而，肺间质水肿的早期诊断是有问题的。我们的初步数据显示，1小时30度头向下倾斜（HDT）导致的肺通气不均匀性的可逆变化，伴随着肺灌注分布的变化，以及肺部功能MRI研究确定的肺部总水量的增加。这种通气和灌注的变化有可能破坏肺部的气体交换。迄今为止的证据表明，这些变化是由HDT引起的肺液平衡改变引起的。我们提出了一系列协调的生理和功能成像研究，以验证以下假设：导致肺间质水肿的肺液体平衡的急性改变将导致通气灌注比、肺含水量、肺周围气体混合和肺血流的变化，并且这些变化可以使用我们采用的技术有效地表征。使用30度头部向下倾斜模型快速引起肺部液体含量的急性增加，我们将：1)使用多重惰性气体消除技术测量肺部通气灌注比（VA/Q）分布的变化，并使用无创测量呼吸内VA/Q。2)确定肺水增加30度HDT时通气分布、肺气体交换和肺力学变化的关系。3)使用功能磁共振成像（fMRI）和x线技术定义和量化肺血流异质性变化与肺水含量之间的关系。

DESCRIPTION (provided by applicant): Our overall goal is to understand the mechanisms by which pulmonary interstitial edema, the precursor to alveolar edema, affects pulmonary gas exchange. Pulmonary interstitial edema in the lung occurs as part of the transition between a healthy "dry" state, and a lung in which alveolar flooding is present. However, the early diagnosis of pulmonary interstitial edema is problematic. Our preliminary data show reversible changes in the inhomogeneity of pulmonary ventilation resulting from 1 hour of 30 degrees head-down tilt (HDT), accompanied by changes in the distribution of pulmonary perfusion, and by an increase in the total amount of water in the lungs determined from functional MRI studies of the lung. Such changes in both ventilation and perfusion have the potential to disrupt gas exchange in the lung. The evidence to date suggests that these changes result from alterations in lung fluid balance resulting from HDT. We propose a coordinated series of physiological, and functional imaging studies to test the hypothesis that the acute alterations in the fluid balance of the lung that result in pulmonary interstitial edema in humans will result in changes in ventilation-perfusion ratio, lung water content, gas mixing in the periphery of the lung, and pulmonary blood flow, and that these changes can be usefully characterized using the techniques we employ. Using a 30 degree head-down tilt model to rapidly provoke an acute increase in fluid content of the lung we will: 1) Measure alterations in the distribution of ventilation-perfusion ratio (VA/Q) in the lung using the multiple inert gas elimination technique, and using non-invasive measurements of intra-breath VA/Q. 2) Determine the relationship between alterations in ventilation distribution, pulmonary gas exchange and pulmonary mechanics as lung water is increased by 30 degree HDT. 3) Define and quantify the relationship between alterations in the heterogeneity of pulmonary blood flow and lung water content using functional magnetic resonance imaging (fMRI) and X-ray techniques.