Pulmonary disposition of lipophilic amine compounds (LAC) in the isolated perfused rabbit lung (IPL)

The lung is a significant reservoir for LAC which associate with different cell types and constituents. The multiple indicator dilution method has the potential for taking advantage of these associations for detecting changes in lung tissue composition. To begin examination of this concept, we measured the pulmonary venous concentration (cone) versus time curves for three LAC, alfentanil (Alf), lidocaine (Lid) and codeine (Cod) after the bolus injection of each amine and a vascular reference indicator into the pulmonary artery of the IPL over a range of flows (F) and perfusate albumin cone ([BSA]). Increasing F decreased the pulmonary extraction (E) of both Cod and Lid, but had little effect on the E of Alf. Increasing [BSA] decreased the E of Alf and Lid, but had virtually no effect on the E of Cod. To evaluate the information content of these data, we developed a kinetic model which interprets the data in terms of amine-tissue interactions. The model parameters reveal rapidly (relative to lung capillary transit rime) equilibrating amine-tissue interactions for Alf, and a combination of rapidly and slowly equilibrating interactions for Cod and Lid. The kinetic parameters descriptive of these interactions were correlated (±) with pKa, lipophilicity, and albumin binding of LAC, consistent with the possibility that such compounds may be used to detect changes in physical-chemical properties of the lung tissue.