Imaging Hypoxic Pulmonary Vasoconstriction in the Aging Lung with Proton MRI

描述(申请人提供)：目的：肺循环是暴露在低氧环境下血管收缩的唯一循环，这种现象被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是确保高效的主要主动机制。肺内气体交换。HPV通过收缩通风不良(低PO2)区域的小动脉，将血液重新分配到通风良好的肺，以及预防 PO2背景：众所周知，通气量的异质性随着年龄的增长而增加，但VA/Q不匹配也会增加，动脉血氧分压也会下降。我们先前的研究发现，健康的衰老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的某种调制正在平衡日益增长的通风异质性，但在一些老年受试者中，HPV存在衰减，影响气体交换效率和氧合。假设：我们将检验这样的假设，即与年轻个体相比，老年患者HPV调节血流从而补偿通气量异质性的能力降低。我们提出了最近发展起来的质子磁共振方法，用于定量测量肺血流、通气量和VA/Q比值的空间分布，以评估肺循环。为了测试个体的HPV活性，我们使用了30%的氧气挑战：如果局部缺氧导致HPV减少局部血流量，呼吸30%的氧气将释放HPV，并增加先前低流量区域的血流量。结果是整体流动的非均质性降低。我们的初步数据显示，30%的氧气降低了30岁以上受试者的血流不均一性，但在30岁以上的受试者中并非如此。目的：1.老年人(45~75岁)和对照组(18~30岁)吸入30%O直接检测HPV的存在。2.在这些受试者中，量化全肺的通气量、VA/Q比值和肺泡O2的空间分布，并与HPV的活性进行比较，以评估HPV在维持气体交换方面的有效性。3.评估HPV对急性刺激、诱发局部缺氧的主动反应能力。我们预测，健康的老年人群将表现出影响VA/Q匹配的HPV减弱。影响：虽然HPV有利于气体交换，但也可能是有害的：在暴露于低氧期间，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患者的肺动脉高压。HPV会增加右心的压力，并可能使临床症状恶化，特别是在存在心力衰竭的情况下。确定正常衰老时HPV变化的程度对于评估HPV在疾病中的潜在作用至关重要。如果丢失了 HPV是健康衰老的正常组成部分，那么检测残留的HPV可能成为肺部疾病和OSA的标准临床检查的一部分，并成为发病率和死亡率的重要预测因子。

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.