PULMONARY DISPOSITION OF LIPOPHILIC AMINE COMPOUNDS IN THE ISOLATED-PERFUSED RABBIT LUNG

We measured the pulmonary venous concentration vs. time curves for [H- 3]alfentanil, [C-14]lidocaine, and [H-3]codeine after the bolus inject ion of each of these lipophilic amine compounds (LAG) and a vascular-r eference indicator (fluorescein isothiocyanatedextran) into the pulmon ary artery of isolated perfused rabbit lungs. A range of flows and per fusate albumin concentrations was studied. To evaluate the information content of the data, we developed a kinetic model describing the pulm onary disposition of these LAC that was based on indicator dilution th eory, and we sought a robust approach for interpreting the estimated m odel parameters. We found that the distribution of the kinetic model r ate constants of the lipophilic amine-tissue interactions can be descr ibed by alpha, H, and psi, where alpha is a measure of the capacity of the rapidly equilibrating interactions between the lipophilic amine a nd the tissue; A is a measure of the equilibrium capacity of the slowl y equilibrating interactions between the Lipophilic amine and the tiss ue. and psi is the mean sojourn time. The values of alpha, H, and psi were 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 va lues for alpha, H, and psi reveal the relative dominance of the slowly equilibrating interactions for lidocaine and codeine in comparison wi th alfentanil. This approach to data analysis may have utility for the potential use of LAC to reveal and to quantify changes in lung tissue composition associated with lung disease.