Abstract
Tidal volume, intrapleural pressure and flow, measured in spontaneously breathing unanesthetized guinea pigs in a body plethysmograph, were processed by an analog computer to give a breath by breath write-out of airway resistance and dynamic lung compliance. This technique has been used to assess responses to isoproterenol or histamine. parenterally or aerosolized. Inulin aerosols were used to estimate the amounts of drug deposited in the lungs. There was a close relationship between exposure time to inulin aerosol and deposition of inulin; 10 mg/ml of inulin aerosolized deposited 1.8 µg of inulin per minute. Compliance decreases with histamine aerosols were dose related. Decreases of compliance by up to 50% were accompanied by small changes in tidal volume and little change in respiratory rate. Higher doses decreased respiratory rate. Resistance increased little after aerosols but markedly after i.v. infusions. A tracheotomy reduced or abolished this resistance increase. Aerosolized histamine reduced compliance in smaller doses than did i.v. histamine. Responses to doses given in random order were reproducible for many hours. The variability of position and slope of the response curves was less after i.v. administration than after aerosols. Responses to histamine, parenterally or aerosoiized, were reduced in animals anesthetized with urethane. Isoproterenol aerosols, in small doses, had minimal effects except in constricted animals when resistance markedly decreased and compliance increased. Isoproterenol i.v. increased flow and slightly increased tidal volunme and compliance but markedly decreased resistance. The results validate use of our methods for the quantitative assessment of responses to bronchoactive agents under physiologicai conditions.
Footnotes
- Received May 27, 1971.
- Accepted September 13, 1971.
- © 1972, by The Williams & Wilkins Company
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