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

• Published in: Journal of applied physiology (1985) 1998-02, Vol.84 (2), p.516-530
• Main Authors: Audi, S. H, Dawson, C. A, Linehan, J. H, Krenz, G. S, Ahlf, S. B, Roerig, D. L
• Format: Article
• Language: English
• Subjects: Air breathing; Alfentanil - administration & dosage; Alfentanil - pharmacokinetics; Animals; Biological and medical sciences; Codeine - administration & dosage; Codeine - pharmacokinetics; Female; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Indicator Dilution Techniques; Injections, Intra-Arterial; Lidocaine - administration & dosage; Lidocaine - pharmacokinetics; Lung - metabolism; Male; Models, Biological; Perfusion; Pulmonary Artery; Rabbits; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Serum Albumin, Bovine - metabolism; Tissue Distribution; Vertebrates: respiratory system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1998.84.2.516

Departments of 1  Biomedical Engineering and of 2  Mathematics, Statistics and Computer Science, Marquette University, Milwaukee, 53201-1881; Departments of 3  Physiology and of 4  Anesthesiology and Pharmacology/Toxicology, Medical College of Wisconsin, Milwaukee, 53226; and 5  Department of Veterans Affairs, Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 Audi, S. H., C. A. Dawson, J. H. Linehan, G. S. Krenz, S. B. Ahlf, and D. L. Roerig. Pulmonary disposition of lipophilic amine compounds in the isolated perfused rabbit lung. J. Appl. Physiol. 84(2): 516-530, 1998. We measured the pulmonary venous concentration vs. time curves for [ 3 H]alfentanil, [ 14 C]lidocaine, and [ 3 H]codeine after the bolus injection of each of these lipophilic amine compounds (LAC) and a vascular-reference indicator (fluorescein isothiocyanate-dextran) 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 , , and , where is a measure of the capacity of the rapidly equilibrating interactions between the lipophilic amine and the tissue; is a measure of the equilibrium capacity of the slowly equilibrating interactions between the lipophilic amine and the tissue; and is the mean sojourn time. The values of , , and 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 , , and 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. codeine; alfentanil; lidocaine; multiple-indicator dilution method The Journal of Applied Physiology 84(2):516-530 8750-7587/98 $5.00 Copyright © 1998 the American Physiological Society