title: Pulmonary inflammation alters the lung disposition of lipophilic amine indicators.
abstract: Many lipophilic amine compounds are rapidly extracted from the blood on passage through the pulmonary circulation. The extent of their extraction in normal lungs depends on their physical-chemical properties, which affect their degree of ionization, lipophilicity, and propensity for interacting with blood and tissue constituents. The hypothesis of the present study was that changes in the tissue composition that occur during pulmonary inflammation would have a differential effect on the pulmonary extraction of lipophilic amines having different properties. If so, measurement of the extraction patterns for a group of lipophilic amines, having different physical-chemical properties, might provide a means for detecting and identifying lung tissue abnormalities. To evaluate this hypothesis, we measured the pulmonary extraction patterns for four lipophilic amines, [(14)C]diazepam, [(3)H]alfentanil, [(14)C]lidocaine, and [(14)C]codeine, along with two hydrophilic compounds, (3)HOH and [(14)C]phenylethylamine, after the bolus injection of these indicators into the pulmonary artery of isolated lungs from normal rabbits and from rabbits with pulmonary inflammation induced by an intravenous injection of complete Freund's adjuvant. The pulmonary extraction patterns, parameterized using a previously developed mathematical model, were, in fact, differentially altered by the inflammatory response. For example, the tissue sequestration rate, k(seq) (ml/s), per unit (3)HOH accessible extravascular lung water volume significantly increased for diazepam and lidocaine, but not for codeine and alfentanil. The results are consistent with the above hypothesis and suggest the potential for using lipophilic amines as indicators for detection and quantification of changes in lung tissue composition associated with lung injury and disease.
authors.affiliation: Biomedical Engineering Department, Marquette University, Milwaukee 53201-1881, Medical College of Wisconsin, Milwaukee 53201-1881, USA. audis@vms.csd.mu.edu
authors.forename: S H
authors.initials: SH
authors.lastname: Audi
authors.forename: D L
authors.initials: DL
authors.lastname: Roerig
authors.forename: S B
authors.initials: SB
authors.lastname: Ahlf
authors.forename: W
authors.initials: W
authors.lastname: Lin
authors.forename: C A
authors.initials: CA
authors.lastname: Dawson
mesh_terms: D000465:Algorithms; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001784:Blood Gas Analysis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003911:Dextrans; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005620:Freund's Adjuvant; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010627:Phenethylamines / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits
chemical_list: D000588:Amines; D003911:Dextrans; D010627:Phenethylamines; C015219:fluorescein isothiocyanate dextran; D005620:Freund's Adjuvant; D053148:Caspase 3; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate