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（肺泡水肿的前驱）影响肺气体交换的机制。肺中的肺间质性水肿作为健康的“干燥”状态与其中存在肺泡泛液的肺之间的过渡的一部分而发生。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，可逆的变化，在肺通气的不均匀性导致1小时的30度头低位倾斜（HDT），伴随着肺灌注的分布变化，并通过增加在肺中的水的总量确定从功能性MRI研究的肺。通气和灌注的这种变化有可能破坏肺中的气体交换。迄今为止的证据表明，这些变化是由于HDT引起的肺液体平衡改变所致。我们提出了一系列协调的生理和功能成像研究，以检验这一假设，即急性改变导致肺间质性水肿的肺液体平衡，在人类将导致通气灌注比，肺含水量，气体混合在肺的周边，和肺血流量的变化，这些变化可以有效地使用我们采用的技术特点。使用30度头低位倾斜模型快速引起肺液体含量的急性增加，我们将：1）使用多种惰性气体消除技术和使用呼吸内VA/Q的非侵入性测量来测量肺中通气-灌注比（VA/Q）分布的改变。2)确定当30度HDT增加肺水时，通气分布、肺气体交换和肺力学变化之间的关系。3)使用功能性磁共振成像（fMRI）和X射线技术定义和量化肺血流异质性和肺水含量变化之间的关系。

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.