Pulmonary disposition of lipophilic amine compounds in the isolated perfused rabbit lung

Audi, S. H., C. A. Dawson, J. H. Linehan, G. S. Krenz, S. B. Ahlf, and D. L. Roerig. Pulmonary disposition of lipophilic aminecompounds in the isolated perfused rabbit lung. J. Appl. Physiol. 84(2): 516-530, 1998.We measured the pulmonaryvenous concentration vs. time curves for [³H]alfentanil,[¹⁴C]lidocaine, and [³H]codeine after thebolus injection of each of these lipophilic amine compounds (LAC) and avascular-reference indicator (fluorescein isothiocyanate-dextran) intothe pulmonary artery of isolated perfused rabbit lungs. A range offlows and perfusate albumin concentrations was studied. To evaluate theinformation content of the data, we developed a kinetic modeldescribing the pulmonary disposition of these LAC that was based onindicator dilution theory, and we sought a robust approach forinterpreting the estimated model parameters. We found that thedistribution of the kinetic model rate constants of the lipophilicamine-tissue interactions can be described by ,, and ,where is a measure of the capacity of the rapidlyequilibrating interactions between the lipophilic amineand the tissue; is a measure of the equilibrium capacity of the slowly equilibrating interactions between the lipophilic amine and the tissue; and isthe mean sojourn time. The values of , , andwere 0.8 ± 0.1 (SE), 0.6 ± 0.1, and 1.6 ± 0.5 s; 1.9 ± 0.1, 5.3 ± 0.4, and 5.6 ± 0.5 s; and 1.1 ± 0.1, 9.8 ± 0.4, and 4.7 ± 0.2 s for alfentanil, lidocaine, and codeine, respectively.These values for , , andreveal the relative dominance of the slowly equilibrating interactions for lidocaine and codeine in comparison with alfentanil. This approachto data analysis may have utility for the potential use of LAC toreveal and to quantify changes in lung tissue composition associatedwith lung disease.