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Abstract
A novel method is described for the reproducible administration of known liquid quantities
to the peripheral airways of the isolated perfused rat lung. The basis of the technique
was to use a 25-microL metered dose of fluorocarbon propellant to expel liquid (as
a coarse spray) from an intratracheal dosing cartridge into the airways, while simultaneously
inflating the lungs with a fixed volume of gas. The methodology is illustrated by
administration of 100-microL volumes of aqueous disodium fluorescein solutions to
a series of lung preparations. The reproducibility and regional distribution of dosing
were determined by dissection, homogenization, and fluorimetric assay. Even though
the dye was distributed nonuniformly between the lung lobes, in a series of preparations,
65.9 +/- 4.8% of the recovered dose was still deposited in the lung periphery, the
site from which absorption is believed to occur. The method will enable the study
of airway-to-perfusate transfer kinetics for compounds administered in a variety of
different liquid formulations.