Silbaugh S A, Stengel P W, Dillard R D, Bemis K G
Department of Connective Tissue & Pulmonary Research, Lilly Research Laboratories, Indianapolis, IN 46285.
J Pharmacol Methods. 1987 Dec;18(4):295-303. doi: 10.1016/0160-5402(87)90061-1.
Airway constriction produced by bronchoconstrictive aerosols in vivo can result in substantial postmortem pulmonary gas trapping in the guinea pig. In order to use gas trapping responses for the evaluation of potential antiasthma agents, we developed a multiple animal inhalation exposure apparatus and an accurate system for quantitating excised lung gas volumes in the guinea pig. Aerosols of histamine, methacholine, and leukotriene D4 were shown to produce gas trapping responses that were inhibited in a dose-dependent fashion by appropriate antagonists. The approach described provides an objective and sensitive measure of the severity of airway obstruction, does not require surgery or anesthesia, and allows excellent control of unwanted sources of experimental variation.
体内支气管收缩气雾剂产生的气道收缩可导致豚鼠死后肺部大量气体潴留。为了利用气体潴留反应来评估潜在的抗哮喘药物，我们开发了一种多动物吸入暴露装置以及一种精确的系统，用于定量豚鼠切除肺的气体体积。组胺、乙酰甲胆碱和白三烯D4气雾剂均显示出能产生气体潴留反应，且这些反应能被适当的拮抗剂以剂量依赖的方式抑制。所描述的方法提供了一种客观且灵敏的气道阻塞严重程度测量方法，无需手术或麻醉，并且能很好地控制不必要的实验变异来源。
