Responses of Contracted Airways and Parenchyma to Stretch in Vivo

体内收缩气道和实质对拉伸的反应

• 批准号: 7312427
• 负责人: Wayne Mitzner
• 金额: $ 45.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7312427
• 关键词: asthma; bronchomotion; clinical research; dogs; mechanical stress; pulmonary respiration; respiratory muscles; respiratory pharmacology; sheep; smooth muscle

It has been suggested that the airway contractile response of asthmatic subjects to a deep inspiration, compared to normal airway dilation seen in healthy subjects, reflects an intrinsic pathophysiology of this disease. Although it is clear that properties of airway smooth muscle must be involved in this functional difference, the properties of the parenchyma that surround the airways may be equally important. This fact suggests that a significant problem in asthma may be related to airway smooth muscle behavior in its dynamic parenchymal environment. This proposal will evaluate mechanisms that underlie this parenchymal-airway interaction, particularly focused on the response to lung inflation and deep inspiration with contracted smooth muscle. This project contains several unique approaches to provide new information on how the lung responds to distension in vivo. First we use a novel method of challenging individual airways that allows us to separate the effects of agonist stimulation on individual airways, the entire airway tree, or the lung parenchyma. Second, by simultaneously using CT imaging with lung impedance measurements, we will be able to completely characterize the airway and dynamic parenchymal viscous and elastic responses. Third, by using a novel challenge method to anesthetize local airway nerves, we can determine how these nerves interact to determine whether the airway will respond with a contraction or relaxation following a deep inspiration. Specific aims of this proposal are designed to test two primary hypotheses related to this airway-parenchymal interaction in vivo: 1) The resultant behavior of airways following lung inflation depends on a balance between opposing physical and chemical effects on the smooth muscle; 2) parenchymal contraction can limit the ability of airways to narrow with pharmacologic or inflation stresses.

已经提出，与在健康受试者中看到的正常气道扩张相比，哮喘患者的气道收缩反应反映了这种疾病的内在病理生理学。尽管很明显，气道平滑肌的特性必须与这种功能差异有关，但围绕气道的实质的特性可能同样重要。这一事实表明，在动态实质环境中，哮喘中的一个重大问题可能与气道平滑肌行为有关。该提案将评估这种实质互动的基础的机制，尤其是针对肺通胀的反应和与合同平滑的深层灵感 肌肉。该项目包含几种独特的方法，以提供有关肺对体内膨胀的反应的新信息。首先，我们使用一种挑战单个气道的新方法，使我们能够将激动剂刺激对单个气道，整个气道树或肺实质的影响分开。其次，通过同时将CT成像与肺阻抗测量值一起使用，我们将能够完全表征气道和动态实质粘性和弹性反应。第三，通过使用一种新颖的挑战方法来麻醉局部气道神经，我们可以确定这些神经如何相互作用以确定 呼吸道是否会在深刻的灵感之后以收缩或放松的方式做出反应。该提案的具体目的旨在测试与这种气道 - 帕克姆相互作用相关的两个主要假设：1）肺通胀后气道的结果行为取决于对平滑肌的物理和化学作用相反的平衡； 2）实质收缩可以限制气道通过药理或通货膨胀应力狭窄的能力。