Lung Perfusion Heterogeneity and Mechanisms of Edema

肺灌注异质性和水肿机制

基本信息

批准号：
7781303
负责人：
Susan R Hopkins
金额：
$ 37.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7781303
关键词：
Acclimatization Acute Affect Altitude Anatomy Area Arts Blood Vessels Blood capillaries Blood flow Characteristics Chronic Confounding Factors (Epidemiology)Development Disease model Doctor of Philosophy Edema Exercise Exhibits Extravascular Lung Water Functional Magnetic Resonance Imaging Global Change Heterogeneity Hypoxia Imaging Techniques Individual Injury Investigation Liquid substance Location Lung Measures Mechanical Stress Organ failure Oxygen Pattern Perfusion Predisposition Process Pulmonary Edema Pulmonary artery structure Recording of previous events Regional Perfusion Reproducibility Research Personnel Resistance Rest Risk Sea Sepsis Spatial Distribution Spin Labels Stress Techniques Testing Time Venous Water Work capillary constriction experience insight interstitial lung injury pressure programs response vasoconstriction

项目摘要

This proposal seeks to understand how spatial heterogeneity in the distribution of pulmonary blood flow and increased pulmonary capillary pressures interact to affect the development of pulmonary edema. High altitude pulmonary edema (HAPE), an acute potentially fatal edema is used as a disease model, to allow investigation of mechanisms of pulmonary edema without confounding variables such as sepsis or multi- organ failure. Mechanical stress injury of the pulmonary capillaries has been shown to be important in the development of HAPE, but how the pulmonary capillaries are exposed to high pressure is unresolved. The overall hypothesis of this proposal is that increased susceptibility to HAPE requires both a hypoxia-induced increase in perfusion heterogeneity and increased pulmonary vascular pressures, resulting in edema in the lung regions of increased flow and pressure. Using a quantitative functional magnetic resonance imaging (fMRI) technique known as arterial spin labeling (ASL) we have previously shown that regional pulmonary blood flow becomes less uniform in a single isogravitational plane during normobaric hypoxia in HAPE suceptible subjects, a finding which is not observed in HAPE resistant subjects, supporting this idea. The effects of hypoxia and exercise on the spatial distribution of pulmonary blood flow will be measured in the entire lung at sea level, using state of the art quantitative fMRI-ASL, and changes related to increased regional extravascular fluid measured with a non-contrast multi echo MR I technique. This will allow insights into the mechanism of the edema, since if the uneven hypoxic pulmonary vasoconstriction is pre-capillary constriction, then the high capillary pressures (and fluid accumulation) will occur in the high flow (less constricted) regions, exposed to the high pulmonary artery pressure due to low arteriolar resistance. A finding of edema in lung regions of low flow would conversely implicate post capillary venoconstriction. The anatomic reproducibility of the pulmonary vascular response will be evaluated to determine whether the pattern of perfusion changes with hypoxia are regionally stable, or whether the regions of high flow change their anatomic location over time. If they are regionally reproducible, this would suggest that there are inherent structural abnormalities in some lung regions, while an anatomically variable response would suggest a predominantly dynamic interdependent process. Finally the effects of acclimatization, and exercise (important modulating factors for HAPE) on the development of increased perfusion heterogeneity and resultant fluid accumulation will be evaluated. The results of these studies may offer insights into how fluid accumulates in the lung under conditions of stress when the pressure in the lung blood vessels is increased and available oxygen is reduced. In particular, by evaluating the the relationship between blood flow and fluid formation in the lung, this work may allow the identification of a threshold for lung injury under certain conditions to be identified and the prediction of those who are at risk for pulmonary edema.

该提议旨在了解肺血流分布中的空间异质性和增加的肺毛细管压力相互作用以影响肺水肿的发展。高的海拔肺水肿（HAPE），一种急性致命水肿作为疾病模型，以允许研究肺水肿的机制，而没有混淆败血症或多种变量器官故障。肺毛细血管的机械应力损伤已被证明在 HAPE的发展，但是肺毛细血管如何暴露于高压。这该提议的总体假设是，增加对HAPE的敏感性需要缺氧引起的灌注异质性的增加和肺血管压力增加，导致水肿流量和压力增加的肺区域。使用定量功能磁共振成像（fMRI）被称为动脉自旋标记（ASL）的技术，我们先前已经表明了区域肺在HAPE中，在正态性缺氧期间，单个同批面的平面中的血流变得不那么均匀令人感知的主题，这是在抗Hape抗性主题中未观察到的发现，支持了这一想法。这缺氧和运动对肺血流的空间分布的影响将在使用最先进的fmri-ASL的状态，在海平面的整个肺部，与增加有关的变化用非对比度多回波MR I技术测量的区域血管外流体。这将允许见解进入水肿的机理，因为如果不均匀的低氧肺血管收缩为毛细血管前收缩，然后在高流量中发生高毛细管压力（和流体积累）（较少狭窄的区域，由于小动脉耐药性低而暴露于高肺动脉压力。一个在低流量的肺部地区发现水肿将暗示毛细血管静脉内收缩后。这将评估肺血管反应的解剖学可重复性，以确定是否是否缺氧的灌注变化模式在区域稳定，或者高流量的区域是否变化随着时间的流逝，他们的解剖位置。如果它们在区域可再现，这表明有某些肺部区域内固有的结构异常，而解剖上可变的反应将提出一个主要动态的相互依存过程。最后，适应性的影响，以及运动（HAPE的重要调节因素）关于灌注异质性增加的发展并将评估所得的液体积累。这些研究的结果可能会提供有关如何当肺血管中的压力是增加和可用的氧气减少。特别是，通过评估血液之间的关系肺中的流量和流体形成，这项工作可以识别在肺部损伤下的阈值某些条件要识别，并预测有肺水肿风险的人。