Imaging Hypoxic Pulmonary Vasoconstriction in the Aging Lung with Proton MRI

使用质子 MRI 对老化肺部的缺氧性肺血管收缩进行成像

• 批准号: 9000558
• 负责人: Susan R Hopkins
• 金额: $ 59.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9000558
• 关键词: Acute; Affect; Age; Aging; Aircraft; Albuterol; Alveolar; Attenuated; Blood; Blood Circulation; Blood flow; Breathing; Bronchoconstriction; Bronchodilation; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Data; Disease; Effectiveness; Elderly; Ensure; Environmental air flow; Equilibrium; Exposure to; Figs - dietary; Financial compensation; Flying body movement; Gases; Goals; Health; Heart; Heart failure; Heterogeneity; Hyperoxia; Hypoxia; Image; Imaging Techniques; Individual; Lung; Lung diseases; Magnetic Resonance Imaging; Measurement; Measures; Methods; Morbidity - disease rate; Obstructive Sleep Apnea; Older Population; Oxygen; Partial Pressure; Pathologic; Patients; Pattern; Perfusion; Phenotype; Protons; Pulmonary Circulation; Pulmonary Gas Exchange; Pulmonary Hypertension; Role; Spatial Distribution; Stimulus; Subjects Selections; Techniques; Testing; Vasodilator Agents; Work; age effect; age group; aged; arteriole; attenuation; cost; drug discovery; healthy aging; human subject; lung imaging; methacholine; mortality; normal aging; novel; pressure; research study; response; vasoconstriction

DESCRIPTION (provided by applicant): Goal: The pulmonary circulation is the only circulation that vasoconstricts when exposed to hypoxia, a phenomenon known as hypoxic pulmonary vasoconstriction (HPV). The goal of this work is to understand how healthy aging affects HPV. This is important because HPV is the major active mechanism ensuring efficient .. pulmonary gas exchange. HPV optimizes ventilation-perfusion (VA/Q ) matching by constricting arterioles in poorly ventilated (low PO2) regions, redistributing blood to well-ventilated lung, and defending PO2 Background: Ventilation heterogeneity is known to increases with age, but VA/Q mismatch also increases and arterial PO2 declines. Our prior studies found that healthy aging is associated with increased spatial heterogeneity in pulmonary blood flow, but also decreased arterial saturation. Together this suggests that some modulation by HPV is balancing a growing heterogeneity of ventilation, but that there is attenuation of HPV in some older subjects, affecting gas exchange efficiency and oxygenation. Hypothesis: We will test the hypotheses that the ability of HPV to modulate blood flow and thus compensate for ventilation heterogeneity is reduced in older compared to younger individuals. We propose recently developed proton MRI methods for quantitative measurement of the spatial distribution of perfusion, ventilation and VA/Q ratio to evaluate the pulmonary circulation. To test for the HPV activity in an individual, we use a 30% oxygen challenge: if local flow is reduced by HPV due to local hypoxia, breathing 30% O2 will release HPV, and increase flow in previously low flow regions. The result is overall flow heterogeneity decreases. Our preliminary data shows that 30% O2 decreases blood flow heterogeneity in subjects <30 y.o., as expected, but not in those aged >30 years. Aims: 1. Directly test for the presence of HPV with inhalation of 30% O in older subjects (45-75+y) and controls (18-30y). 2. In these subjects, quantify the spatial distribution of ventilation, VA/Q ratio and alveolar O2 in the entire lung and compare to the HPV activity, to assess the effectiveness of HPV in maintaining gas exchange and 3. Evaluate the ability of HPV to actively respond to an acute stimulus .inducing regional hypoxia. We predict that healthy older populations will show an attenuation of HPV affecting VA/Qmatching. Impact: Although beneficial for gas exchange, HPV may also be detrimental: During exposure to hypoxia such as during in patients with obstructive sleep apnea (OSA), HPV raises pulmonary arterial pressure and may contribute to pulmonary hypertension in OSA. HPV increases right heart strain and may worsen the clinical picture, particularly if heart failure is present. Establishing the extent f changes with normal aging is essential to evaluate the potential role of HPV in disease. If loss of HPV is a normal part of healthy aging, then testing for retained HPV may become part of a standard clinical workup in lung disease and OSA, and an important predictor of morbidity and mortality.

描述（由申请人提供）：目的：肺循环是暴露于缺氧时血管收缩的唯一循环，这种现象称为缺氧性肺血管收缩（HPV）。这项工作的目标是了解健康老龄化如何影响HPV。这一点很重要，因为HPV是确保有效的主要活性机制。肺气体交换HPV通过收缩通气不良（低PO 2）区域的小动脉，将血液重新分配到通气良好的肺，并保护肺组织，优化通气-灌注（VA/Q）匹配。 PO 2背景：已知通气异质性随年龄增加而增加，但VA/Q不匹配也增加，动脉PO 2下降。我们先前的研究发现，健康老龄化与肺血流的空间异质性增加有关，但也与动脉饱和度降低有关。总之，这表明HPV的一些调节正在平衡通气的日益增长的异质性，但在一些老年受试者中HPV减弱，影响气体交换效率和氧合。 假设：我们将测试的假设，即HPV的能力，以调节血流，从而补偿通气异质性是减少老年人相比，年轻人。我们建议最近开发的质子MRI方法定量测量的空间分布的灌注，通气和VA/Q比，以评估肺循环。为了测试个体中的HPV活性，我们使用30%的氧气挑战：如果由于局部缺氧而导致局部流量减少，则呼吸30%的O2将释放HPV，并增加先前低流量区域的流量。其结果是整体流动不均匀性降低。我们的初步数据显示，30% O2可降低<30岁受试者的血流异质性，如预期，但在年龄>30岁的患者中并非如此。 目的：1.在老年受试者（45-75岁）和对照组（18- 30岁）中吸入30% O直接检测HPV的存在。2.在这些受试者中，量化整个肺中通气量、VA/Q比和肺泡O2的空间分布，并与HPV活性进行比较，以评估HPV在维持气体交换方面的有效性。评估HPV对急性刺激的积极反应能力。诱导局部缺氧。我们预测，健康的老年人群将显示HPV的衰减影响VA/Q匹配。 影响力：虽然对气体交换有益，但HPV也可能是有害的：在暴露于缺氧期间，如阻塞性睡眠呼吸暂停（OSA）患者，HPV会升高肺动脉压，并可能导致OSA的肺动脉高压。HPV会增加右心压力，并可能使临床症状恶化，特别是在存在心力衰竭的情况下。确定正常衰老的变化程度对于评估HPV在疾病中的潜在作用至关重要。如果损失 HPV是健康衰老的正常组成部分，那么残留HPV的检测可能成为肺部疾病和阻塞性睡眠呼吸暂停综合症标准临床检查的一部分，也是发病率和死亡率的重要预测因素。