AIRFLOW-INDUCED RESPONSES IN THE LUNG PERIPHERY

肺周围气流引起的反应

基本信息

批准号：
3471627
负责人：
Arthur N Freed
金额：
$ 12.03万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 1993-08-31
项目状态：
已结题

项目摘要

The goal of the proposed research is to investigate the mechanisms through which increased airflow alters the collateral system resistance (Rcs) in the canine lung periphery. The central hypothesis is that the collateral system response to increased airflow is a direct function of evaporative water loss. The underlying mechanism may involve either airway cooling or airway drying (i.e., changes in the osmotic environment of the pulmonary mucosa). These changes could trigger a cascade of events that lead to a number of alternative pathways that affect Rcs. Each pathway could act simultaneously and synergistically to stimulate mediator release, trigger muscarinic or adrenergic activity, or directly affect airway smooth muscle and epithelium. Experiments are described in which an animal model is used to examine various mechanisms that may be involved in exercise, cold air, and hyperventilation induced bronchospasm. The specific objectives of this research are to: 1) Define the stimulus responsible for airflow induced bronchospasm (AIB); 2) Determine the effect of AIB on peripheral airway reactivity; 3) Administer pharmacologic agents that modify the response of the collateral system to challenge with dry air; 4) Determine the role of pulmonary and bronchial circulations in AIB; 5) Examine in vivo/in vitro correlations of AIB; and 6) Characterize delayed or late responses to dry air challenge. Experiments will utilize 1) the wedged bronchoscope technique to monitor Rcs, deliver aerosols, and challenge the lung periphery with increased rates of airflow; 2) specially designed thermisters and probes to monitor airway wall temperature (Taw) and the osmolarity of airway fluids, respectively; 3) bronchoalveolar lavage to examine the effect of high flow on cell profiles and mediator release; and 4) various pharmacologic and nonpharmocologic agents in an attempt to alter in vivo responses to increased airflow, and alter in vitro responses of smooth muscle and parenchyma following a variety of challenges. The response of the peripheral lung to increased airflow is of particular interest considering the fact that many asthmatics exhibit small airways obstruction following a period of exercise. The results of this study should provide a more complete understanding of the underlying mechanisms responsible for airflow-induced responses of the airways.

拟议研究的目标是调查增加气流改变抵押品的机制犬肺周围的系统阻力（Rcs）。中央假设是抵押系统对增加的反应气流是蒸发水损失的直接函数。这潜在机制可能涉及气道冷却或气道干燥（即，渗透环境的变化肺粘膜）。这些变化可能会引发一连串的导致许多影响替代途径的事件参考资料。每个途径可以同时协同作用刺激介质释放，触发毒蕈碱或肾上腺素能活动，或直接影响气道平滑肌和上皮。描述了使用动物模型来进行的实验检查运动中可能涉及的各种机制，冷空气和过度换气引起的支气管痉挛。具体的本研究的目标是： 1) 定义刺激负责气流诱发的支气管痉挛（AIB）； 2）确定 AIB 对周围气道反应性的影响； 3）管理改变抵押反应的药物用干燥空气挑战的系统； 4）确定角色 AIB 中的肺和支气管循环； 5）检查 AIB 的体内/体外相关性； 6) 表征延迟或对干燥空气挑战的反应迟缓。实验将利用1) 楔形支气管镜技术可监测 Rcs，提供气溶胶，并以增加的速率挑战肺周围空气流动; 2）专门设计的热敏电阻和探头来监测气道壁温度 (Taw) 和气道渗透压分别为液体； 3）支气管肺泡灌洗检查高流量对细胞特征和介质释放的影响；和 4) 尝试各种药物和非药物制剂改变体内对气流增加的反应，并改变体外平滑肌和实质细胞在各种变化后的反应的挑战。周围肺对增加的反应考虑到许多哮喘患者在一段时间后会表现出小气道阻塞锻炼。这项研究的结果应该提供更多完全理解负责的底层机制用于气流引起的气道反应。