Abstract

A study was made of the uptake and metabolism of various amines by isolated perfused rabbit lungs, artificially ventilated and perfused via the pulmonary artery with heparin-treated. autologous whole blood. Pulmonary hemodynamics remained constant and lung morphology was normal during 2 hours of perfusion. The basic amines (pK_a > 8.5) were accumulated to a much greater extent than the nonbasic amines (pK_a < 7.0). When added to the perfusion fluid in amounts of 0.2 to 100 µmol (2-1000 µM), chlorcyclizine. methadone, imipramine and amphetamine were highly accumulated (50-95% of a dose) by the lungs, whereas aniline, imidazole and propazine were poorly accumulated (10-20% of a dose). The uptake of all chemicals tested was rapid and a steady state was reached in 10 minutes. The quaternary ammonium compound paraquat was not accumulated by the lungs. but all concentrations used caused massive edema. The accumulation of the basic amines, chlorcyclizine, methadone, imipramine and amphetamine, involved a concentration-dependent uptake process, whereas the accumulation of the nonionized, neutral amines, aniline, imidazole and propazine, was nonsaturable and probably involved diffusion. None of the amines studied, except methadone, were apparently metabolized by the lungs during the 60 minutes of perfusion. The results indicate that rabbit lungs can be regarded as an important site of storage for basic amines and that the isolated perfused rabbit lung accumulated several basic chemicals and drugs that others have shown to localize or concentrate in lung tissue in vivo. The perfused rabbit lung may be useful in studying the mechanisms of such concentration of chemicals by the lung.