MORPHOLOGICAL CORRELATES OF AIRWAY CONTRACTION

气道收缩的形态相关性

• 批准号: 3349903
• 负责人: ALAN Richard LEFF
• 金额: $ 8.43万
• 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 1986-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349903
• 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; 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.

气管内径的原位变化与体外变化的关系 对收缩的气道平滑肌力的测量仍不清楚。 这些调查的目的是确定 慢性阻塞性肺疾病致气道内径原位改变的相互关系 生理和药理刺激以及体外生理学， A)等长平滑肌的生化和形态测量 收缩，b)受体密度，c)平滑肌质量，以及d) 肺内力。将进行三组实验。1) 对药物和生理刺激的分级反应曲线将 在麻醉犬身上产生，经丹那胺支气管造影术评估为 第0代到第5代的同时改变呼吸道口径(DAW) 在每一级刺激下。同样的呼吸道将被切除 术中测量的准确位置的等距固定 支气管镜检查。浓度-反应曲线将在体外产生 与来自同一只狗的DAW的变化相关。2)在 单独的实验，从第0代到第5代的呼吸道部分将 最初切除，并对呼吸道反应进行等长测量 乙酰甲胆碱、组胺、5-羟色胺、肾上腺素和氯化钾 是在体外产生的。来自每个呼吸道的连续组织将固定在 福尔马林用于计算机形态计量学测定支气管平滑 肌肉发达。每个呼吸道的收缩力将被评估为 肌群功能：收缩力。此外，地区性 受体密度的差异，肺相互依赖的作用和 将确定气道口径净变化时的气道弹性，并 与第一节中获得的现场数据相关联。几何 将评估每一代呼吸道的肌肉方向，并 与平滑肌收缩的力度和效率有关。3)在 最后一组实验，将获得连续的支气管条 在第2节中，用于通过配基结合和 放射自显影技术。受体密度与 现场生理反应将被确定为平滑的函数 肌肉发达。从这些研究中得出的数据将定义生理学 以及这些相关性的药理学意义 肺的阻力支气管炎。形态测量和生化数据将 从呼吸道角度进一步定义支气管收缩的效率 平滑肌质量和气道平滑肌的几何取向。 这些数据将阐明决定支气管运动张力的机制。 正常人和哮喘患者。