AIRWAY RESPONSE--MECHANICAL DETERMINANTS AND MA TURATION

气道反应——机械决定因素和成熟度

• 批准号: 3367623
• 负责人: Robert S. Tepper
• 金额: $ 24.84万
• 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/3367623
• 关键词: asthma; basement membrane; bronchospasm; elastin; growth /development; immature animal; laboratory rabbit; lung alveolus; 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机制 这有助于婴儿期和婴儿期之间的反应性下降 青春期，婴儿的气道反应性提高 和年龄较大的儿童生命早期肺部受伤。 正常婴儿 成人哮喘患者表现出更大的最大气道在 对支气管收缩的反应比正常成年人的反应。 机械力 在气道和肺实质中，以及 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 这些力之间的平衡随着成熟的成熟而改变 肺，这些力量早期的改变导致 大龄儿童和成人的气道反应性提高。 具体 该项目的目的是1）确定与年龄有关的程度 气道电阻和组织电阻的响应差异 使用动物模型到甲基苯胺，2）比较气道范围 在未成熟和成熟动物中相互依存，3）确定 实质性肺损伤早期生命早期对气道反应性的影响 成熟的动物和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。 牙槽胶囊技术将用于分割 对气道和组织成分的肺耐药性。 生理 成熟和未成熟动物的测量将与 气道口径，气道壁厚度的形态计算评估， 气道平滑肌，弹性蛋白以及牙槽大小和形状的数量。 气道 - 范式相互依存将通过生理评估 和对气道狭窄的形态计量计算在不同的肺部 卷。 未成熟动物的实质损伤将与 气体内弹性酶和胶原酶，当动物成熟时， 将获得生理和形态计量测量。