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

S. H. Audi*, C. A. Dawson, J. H. Linehan, G. S. Krenz, S. B. Ahlf, D. L. Roerig

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

We measured the pulmonary venous concentration vs. time curves for [3H]alfentanil, [14C]lidocaine, and [3H]codeine after the bolus injection of each of these lipophilic amine compounds (LAC) and a vascular-reference indicator (fluorescein isothiocyanatedextran) into the pulmonary artery of isolated perfused rabbit lungs. A range of flows and perfusate albumin concentrations was studied. To evaluate the information content of the data, we developed a kinetic model describing the pulmonary disposition of these LAC that was based on indicator dilution theory, and we sought a robust approach for interpreting the estimated model parameters. We found that the distribution of the kinetic model rate constants of the lipophilic amine- tissue interactions can be described by α, H, and Ψ, where α is a measure of the capacity of the rapidly equilibrating interactions between the lipophilic amine and the tissue; H is a measure of the equilibrium capacity of the slowly equilibrating interactions between the lipophilic amine and the tissue; and Ψ is the mean sojourn time. The values of α, H, and Ψ 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 values for α, H, and Ψ reveal the relative dominance of the slowly equilibrating interactions for lidocaine and codeine in comparison with 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.

Original languageEnglish (US)
Pages (from-to)516-530
Number of pages15
JournalJournal of applied physiology
Volume84
Issue number2
DOIs
StatePublished - Feb 1998

Keywords

  • Alfentanil
  • Codeine
  • Lidocaine
  • Multiple-indicator dilution method

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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