An isolated perfused rat lung preparation for the study of aerosolized drug deposition and absorption.

The isolated, perfused rat lung preparation was modified to allow characterized solid aerosol delivery. Deposition and airway-to-perfusate transfer of disodium fluorescein from 3-4 micron dae solid aerosols were studied under different ventilatory regimes. The lungs inhaled from an aerosol stream of constant concentration via a tracheal cannula. Air displacement from a sealed artificial thorax housing the lungs provided the driving force for inhalation. The lungs were suspended in a physiologically normal position and both left and right sides of the heart were cannulated for constant rate perfusate flow. Fractional deposition was inversely proportional to respiratory frequency implying that sedimentation was the primary deposition mechanism. Increasing tidal volumes similarly enhanced the ratio of amount deposited/amount administered. Fluorescein transfer to the perfusate occurred from the lung regions containing intact vasculature, was apparent first-order, and independent of perfusate flow. The average rate constant for transfer was 0.057 +/- 0.02 min-1 (t1/2 = 12.2 +/- 4.2 min-1). The ratio of transferable amount/amount deposited appeared to indicate the depth of aerosol penetration. This increased at high respiratory frequency and tidal volume, while decreasing with increasing aerosol particle size. Potential applications of the model are discussed in the light of these results.