AIR CONDITIONING BY THE TRACHEA--STIMULI AND MECHANISMS

锻炼和在冷干空气中过度换气(CDA)是很重要的 触发哮喘发作，影响80%的哮喘患者。 正常人CDA过度换气后也可见支气管收缩 受试者和实验动物。运动性哮喘和哮喘的主要刺激因素 CDA引起的支气管痉挛是指呼吸道的热量和水分流失， 从而导致呼吸道衬里液体的冷却和高张。AS 通气量增加，气管成为热量的主要来源 调节吸入空气所需的水。呼吸道反应 对于干燥的空气通风，寒冷和高渗刺激较差 明白了。这些反应对于我们理解 哮喘的病理生理学和条件反射的正常过程 空气。这些研究将检验：1)反应和2)死亡机制 麻醉犬气管内冷刺激和高渗刺激3) 水从血管系统进入气流的决定因素 在气管调节空气的过程中，以及4)运动 高渗气管壁中的大分子穿透 解决办法。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。温度为38、26或18摄氏度的液体，以及 将325,900或1800毫微米的渗透压注入气管 细分市场。特别是，对答复的质量差异在 不同的渗透压，以及冷却和高渗之间的任何协同作用 我们将寻找刺激因素。系列2将探讨涉及到的机制 这些反应，着眼于神经控制和几类 调解人。在系列3中，犬的原位气管将暴露在38 空气以恒定的流量向一个方向流动，与水在一起 含量从46毫克/升(100%饱和)到0毫克/升。这水 流向气流、温度以及血管和平滑肌的流量 将在这些明确定义的条件下监测反应。这个 控制水通量速率的因素，特别是 将检查上皮离子泵和气管血流量。在……里面 系列4大分子在气管上皮和气管内的运动 血管系统将在体内和体外雪貂气管中进行研究。在……里面 特别是，将寻找上皮通透性的标志物， 这些标志物在暴露于高渗溶液期间的行为将是 学习。从这些研究中，我们对干燥空气的影响有了更清晰的了解， 以及它的成分刺激，将会出现。这可能会提高我们的理解 对哮喘的治疗，并导致我们对运动诱导的治疗的改进 哮喘。

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.