AIR CONDITIONING BY THE TRACHEA--STIMULI AND MECHANISMS

气管调节空气——刺激和机制

• 批准号: 3082750
• 负责人: Mark E Deffebach
• 金额: $ 7.99万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3082750
• 关键词: asthma; body water; body water dehydration; cold temperature; dogs; electron microscopy; exercise; ferrets; fluid flow; fluorescence microscopy; fluorescence spectrometry; heat; ion transport; membrane permeability; neural information processing; pathology; pulmonary respiration; respiratory airflow measurement; respiratory airway pressure; respiratory circulation; respiratory epithelium; respiratory muscles; sports medicine; trachea; ultraviolet spectrometry; vascular smooth muscle; vascular smooth muscle nervous control

Exercise and hyperventilation with cold dry air (CDA) are important triggers of an asthmatic attack that affects 80% of asthmatics. Bronchoconstriction is also seen after CDA hyperventilation in normal subjects and experimental animals. The major stimuli of exercise asthma and CDA induced bronchospasm are heat and water loss from the airways, resulting in cooling and hypertonicity of the airway lining fluid. As ventilation increases, the trachea becomes a major source of the heat and water required for the conditioning of inspired air. The airway responses to dry air ventilation, and cold and hypertonic stimuli are poorly understood. These responses are important for our understanding of the pathophysiology of asthma, and the normal process of conditioning inspired air. These studies will examine: 1) the responses and 2) die mechanisms of cold and hypertonic stimuli in the trachea of anesthetized dogs, 3) the determinants of water movement from the vasculature into the airstream during the conditioning of air by the trachea, and 4) the movement of macromolecules through the tracheal wall during exposure to hypertonic solutions. In series 1 and 2 the trachea will be isolated in-situ with monitoring of the smooth muscle and vascular tone, and selected epithelial functions. Fluid with temperatures of 38, 26, or 18 degrees C, and osmolalities of 325,900, or 1800 mosM are instilled into the tracheal segment. In particular, qualitative differences to the responses at different osmolalities, and any synergy between the cooling and hypertonic stimuli will be looked for. Series 2 will probe the mechanisms involved in these responses, looking at nervous control and several classes of mediators. In series 3 the in-situ canine trachea will be exposed to 38 degrees C air flowing in one direction at constant flow, with the water content varied from 46 mg/liter (100% saturated), to 0 mg/liter. The water flux into the airstream, temperature, and vascular and smooth muscle responses will be monitored under these well defined conditions. The factors which control the rate of water flux, particularly the role of epithelial ion pumping and the tracheal blood flow , will be examined. In series 4 the movement of macromolecules across the tracheal epithelium and vasculature will be studied in the in-vivo and in-vitro ferret trachea. In particular, markers for epithelial permeability will be looked for, and the behavior of these markers during exposure to hypertonic solutions will be studied. From these studies a clearer picture of the effects of dry air, and its component stimuli, will emerge. This may improve our understanding of asthma, and lead to improvements in our therapy of exercise induced asthma.

运动和冷干空气（CDA）的过度通气很重要 80%的哮喘患者都是哮喘发作的诱因 正常人CDA过度通气后也可见支气管收缩。 实验对象和实验动物。运动性哮喘的主要刺激因素 CDA引起的支气管痉挛是气道的热量和水分损失， 导致气道衬里流体的冷却和高渗。作为 通风增加，气管成为主要的热源， 调节吸入空气所需的水。气道反应 干燥的空气通风，冷和高渗刺激是差 明白这些反应对于我们理解 哮喘的病理生理学和正常的调节过程 空气这些研究将检查：1）反应和2）死亡机制 冷和高渗刺激麻醉犬的气管，3） 水从脉管系统进入气流的决定因素 在通过气管调节空气的过程中，以及4） 暴露于高渗时大分子通过气管壁 解决方案在系列1和2中，气管将被原位分离， 监测平滑肌和血管张力，以及选定的上皮细胞 功能协调发展的温度为38、26或18摄氏度的流体，以及 将325，900或1800 mosM的渗透压浓度滴入气管 片段特别是，在质量上的差异， 不同的渗透压，以及冷却和高渗之间的任何协同作用 将寻找刺激。系列2将探讨涉及的机制， 这些反应，着眼于神经控制和几类 调解员在系列3中，原位犬气管将暴露于38 摄氏度的空气以恒定的流量沿一个方向流动， 含量从46毫克/升（100%饱和）变化到0毫克/升。水 进入气流的流量、温度、血管和平滑肌 将在这些明确规定的条件下监测反应。的 控制水通量速率的因素，特别是 上皮细胞离子泵和气管血流将被检查。在 系列4大分子穿过气管上皮的运动， 将在体内和体外雪貂气管中研究脉管系统。在 特别是，将寻找上皮渗透性的标志物， 这些标记物在暴露于高渗溶液期间的行为将 研究了从这些研究中可以更清楚地看到干燥空气的影响， 及其组成刺激，就会浮现出来。这可能会增进我们对 哮喘，并导致改善我们的治疗运动引起的 哮喘