AIRWAY RESPONSE: MECHANICAL DETERMINANTS AND MATURATION

气道反应：机械决定因素和成熟度

• 批准号: 3367624
• 负责人: Robert S. Tepper
• 金额: $ 24.02万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-13 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3367624
• 关键词: asthma; basement membrane; bronchospasm; elastin; growth /development; immature animal; laboratory rabbit; lung alveolus; lung injury; mature animal; methacholine; muscle contraction; myosins; respiratory airway pressure; respiratory airway volume; respiratory function; respiratory muscles; respiratory pharmacology; smooth muscle

The long term objectives of this project are to understand the mechanisms that contribute to the decline in airway reactivity between infancy and adolescence, and the presence of heightened airway reactivity in infants and older children following lung injury early in life. Normal infants and adult asthmatics demonstrate greater maximal airway narrowing in response to bronchoconstrictors than do normal adults. Mechanical forces in the airways and the lung parenchyma, and the interdependence between these forces, are significant determinants of the decrease in airway caliber that occurs in response to bronchoconstrictors. We hypothesize that the balance between these forces change with the maturation of the lung, and that an alteration of these forces early in life results in heightened airway reactivity in older children and adults. The specific aims of this project are 1) to determine the extent of age-related differences in the responses of airway resistance and tissue resistance to methacholine using an animal model, 2) to compare airway-parenchymal interdependence in the immature and mature animal, 3) to determine the effects of parenchymal lung injury early in life on airway reactivity in the mature animal, and 4) to compare the static and the dynamic contractile properties of immature and mature rabbit airway smooth muscle. An alveolar capsule technique will be used to partition pulmonary resistance into airway and tissue components. Physiologic measurements in mature and immature animals will be correlated with morphometric assessments of airway caliber, airway wall thickness, quantity of airway smooth muscle, elastin, and alveolar size and shape. Airway-parenchymal interdependence will be evaluated through physiologic and morphometric assessments of airway narrowing at different lung volumes. Parenchymal injury in the immature animal will be produced with intra-tracheal elastase and collagenase, and when the animals are mature, physiologic and morphometric measurements will be obtained.

该项目的长期目标是了解其机制 导致婴儿期和婴儿期之间气道反应性下降 青春期和婴儿气道反应性增强 以及早年遭受肺损伤的年龄较大的儿童。 正常婴儿 成人哮喘患者表现出更大的最大气道狭窄 对支气管收缩药的反应比正常成年人要好。 机械力 在气道和肺实质中，以及它们之间的相互依赖性 这些力是气道减少的重要决定因素 响应支气管收缩剂而发生的口径。 我们假设 这些力量之间的平衡随着技术的成熟而改变 肺，并且这些力量在生命早期的改变会导致 年长儿童和成人气道反应性增强。 具体的 该项目的目标是 1) 确定与年龄相关的程度 气道阻力和组织阻力反应的差异 使用动物模型与乙酰甲胆碱比较，2) 比较气道实质 未成熟和成熟动物的相互依赖性，3) 确定 生命早期肺实质损伤对气道反应性的影响 成熟动物，4）比较静态和动态 未成熟和成熟兔气道平滑的收缩特性 肌肉。 肺泡囊技术将用于分区 肺阻力进入气道和组织成分。 生理 成熟和未成熟动物的测量结果将与 气道口径、气道壁厚度的形态测量评估， 气道平滑肌、弹性蛋白的数量以及肺泡的大小和形状。 气道实质相互依赖性将通过生理学评估 不同肺部气道狭窄的形态测量评估 卷。 未成熟动物的实质损伤将由 气管内弹性蛋白酶和胶原酶，当动物成熟时， 将获得生理和形态测量。