Pulmonary inflammation alters the lung disposition of lipophilic amine indicators

Many lipophilic amine compounds are rapidly extracted from the blood on pas sage through the pulmonary circulation. The extent of their extraction in n ormal lungs depends on their physical-chemical properties, which affect the ir degree of ionization, lipophilicity, and propensity for interacting with blood and tissue constituents. The hypothesis of the present study was tha t changes in the tissue composition that occur during pulmonary inflammatio n would have a differential effect on the pulmonary extraction of lipophili c amines having different properties. If so, measurement of the extraction patterns for a group of lipophilic amines, having different physical-chemic al properties, might provide a means for detecting and identifying lung tis sue abnormalities. To evaluate this hypothesis, we measured the pulmonary e xtraction patterns for four lipophilic amines, [C-14]diazepam, [H-3]alfenta nil, [C-14]lidocaine, and [C-14]codeine, along with two hydrophilic compoun ds, (HOH)-H-3 and [C-14]phenylethylamine, after the bolus injection of thes e indicators into the pulmonary artery of isolated lungs from normal rabbit s and from rabbits with pulmonary inflammation induced by an intravenous in jection of complete Freund's adjuvant. The pulmonary extraction patterns, p arameterized using a previously developed mathematical model, were, in fact , differentially altered by the inflammatory response. For example, the tis sue sequestration rate, k(seq) (ml/s), per unit (HOH)-H-3 accessible extrav ascular lung water volume significantly increased for diazepam and lidocain e, but not for codeine and alfentanil. The results are consistent with the above hypothesis and suggest the potential for using lipophilic amines as i ndicators for detection and quantification of changes in lung tissue compos ition associated with lung injury and disease.