MORPHOLOGICAL CORRELATES OF AIRWAY CONTRACTION

气道收缩的形态相关性

• 批准号: 3349907
• 负责人: ALAN Richard LEFF
• 金额: $ 8.27万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349907
• 关键词: autoradiography; bronchoconstrictors; bronchomotion; electrostimulus; epinephrine; histamine; histology; methacholine; muscle contraction; neural information processing; piperazines; respiratory airway pressure; respiratory muscles; respiratory pharmacology; smooth muscle; trachea; tritium; vagotomy

The relationship between in situ changes in airway caliber and in vitro measurements of force of airway smooth muscle contracted remains unknown. The objective of these investigations is to determine the interrelationships between in situ changes in airway caliber induced by physiological and pharmacological stimuli and in vitro physiological, biochemical and morphological measurements of a) isometric smooth muscle contraction, b) receptor density, c) smooth muscle mass, and d) intrapulmonary forces. Three sets of experiments will be performed. 1) Graded response curves to pharmacological and physiological stimuli will generated in anesthetized dogs and assessed by tanatalum bronchography as change in airway caliber (Daw) simultaneously for generations 0 through 5 at each level of stimulation. The same airways will be excised for isometric fixation at the exact site measured during tantalum bronchography. Concentration-response curves will be generated in vitro and correlated to changes in Daw derived from the same dogs. 2) In separate experiments, sections of airway from generations 0 through 5 will be excised initially, and isometric measurements of airway response to methacholine, histamine, serotonin, epinephrine and potassium chloride will be generated in vitro. Contiguous tissue from each airway will be fixed in formalin for compuuterized morphometric determination of bronchial smooth muscle mass. Force of contraction for each airway will be assessed as a function of muscle mass: contractile force. Additionally, regional differences in receptor density, the role of lung interdependence and airway elastance on net changes in airway caliber will be determined and correlated with in situ data derived in Section 1. The geometric orientation of muscle for each generation of airway will be assessed and related to force and efficiency of smooth muscle contraction. 3) In a final set of experiments, contiguous strips of bronchus will be obtained as in section 2 for analysis of receptor density by ligand binding and autoradiographic techniques. Correlation of receptor density to physiological response in situ will be determined as a function of smooth muscle mass. Data derived from these studies will define the physiological and pharmacological significance of these correlates for the major resistance bronchi of the lung. Morphometric and biochemical data will define further the efficiency of bronchial contraction in terms of airway smooth muscle mass and geometric orientation of airway smooth muscle. These data will elucidate mechanisms that determine bronchomotor tone in normal and asthmatic humans.

气道内径的原位变化与体外实验的关系 气道平滑肌收缩力的测量仍然未知。 这些调查的目的是确定 诱发的气道口径原位变化之间的相互关系 生理和药理学刺激以及体外生理， a）等长平滑肌的生物化学和形态学测量 收缩，B）受体密度，c）平滑肌质量，和d） 肺内力 将进行三组实验。 第一章 对药理学和生理学刺激的分级反应曲线将 在麻醉的狗中产生，并通过tanatalum支气管造影评估为 第0代至第5代同时发生气道口径（Daw）变化 在每一个刺激水平。 相同的气道将被切除， 钽电极植入期间测量的准确部位的等长固定 支气管造影 将在体外生成浓度-响应曲线 并与来自相同犬的Daw变化相关。 2)在 单独的实验中，从第0代到第5代的气道部分将 首先切除，并等距测量气道反应， 乙酰甲胆碱，组胺，血清素，肾上腺素和氯化钾将 在体外产生。 将每个气道的接触组织固定在 福尔马林法测定支气管平滑肌的计算机形态学 肌肉质量. 每个气道的收缩力将被评估为 肌肉质量的功能：收缩力。 此外，区域 受体密度的差异，肺相互依赖的作用， 将确定气道弹性对气道口径净变化的影响， 与第1节中得出的原位数据相关。 几何 将评估每一代气道的肌肉方向， 与平滑肌收缩的力和效率有关。 3)中 在最后一组实验中，将获得连续的支气管条带， 在第2节中，通过配体结合分析受体密度， 放射自显影技术。 受体密度与 原位生理反应将被确定为平滑的函数， 肌肉质量. 从这些研究中获得的数据将定义生理 和药理学意义，这些相关的主要 肺的阻力支气管。 形态测量和生化数据将 进一步定义支气管收缩的气道效率 平滑肌质量和气道平滑肌的几何方向。 这些数据将阐明决定支气管张力的机制， 正常人和哮喘患者。