The Effect of Pulmonary Interstitial Edema on Gas Exchange

描述(申请人提供)：我们的总体目标是了解肺间质水肿的机制，肺间质水肿是肺泡水肿的先兆，它影响肺气体交换。肺间质水肿是在健康的“干燥”状态和出现肺泡淹水的肺之间的过渡过程中发生的。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，30度头低位倾斜(HDT)1小时引起的肺通气不均的可逆变化，伴随着肺血流分布的变化，以及肺功能MRI研究确定的肺内总水量的增加。这种通气量和灌注量的变化都有可能扰乱肺部的气体交换。到目前为止的证据表明，这些变化是由于HDT引起的肺液平衡的改变。我们提出了一系列协调的生理和功能成像研究，以检验这样一种假设，即导致人类肺间质水肿的肺液体平衡的急性变化将导致呼吸-灌流比、肺水含量、肺周围气体混合和肺血流量的变化，并且这些变化可以利用我们所使用的技术来有效地表征。利用30度头低位倾斜模型快速引起肺内液体含量的急剧增加，我们将：1)使用多次惰性气体排出技术测量肺内通风/灌流比(VA/Q)分布的变化，并使用无创性测量呼吸内VA/Q。2)确定当肺水量增加30度HDT时，肺内通风分布、肺气体交换和肺力学改变之间的关系。3)应用功能磁共振成像(FMRI)和X线技术确定并量化肺血流异质性改变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.