Detection of changes in lung tissue properties with multiple-indicator dilution

We evaluated the potential utility of a group of indicators, each of which targets a particular tissue property, as indicators in the multiple-indicat or dilution method to detect and to identify abnormalities in lung tissue p roperties resulting from lung injury models. We measured the pulmonary veno us outflow concentration vs. time curves of [C-14]diazepam, (HOH)-H-3, [C-1 4]phenylethylamine, and a vascular reference indicator following their bolu s injection into the pulmonary artery of isolated perfused rabbit lungs und er different experimental conditions, resulting in changes in the lung tiss ue composition. The conditions included granulomatous inflammation, induced by the intravenous injection of complete Freund's adjuvant (CFA), and intr atracheal fluid instillation, each of which resulted in similar increases i n lung wet weight. Each of these conditions resulted in a unique pattern am ong the concentration vs. time outflow curves of the indicators studied. Th e patterns were quantified by using mathematical models describing the pulm onary disposition of each of the indicators studied. A unique model paramet er vector was obtained for each condition, demonstrating the ability to det ect and to identify changes in lung tissue properties by using the appropri ate group of indicators in the multiple-indicator dilution method. One chan ge that was particularly interesting was a CFA-induced change in the dispos ition of diazepam, suggestive of a substantial increase in peripheral-type benzodiazepine receptors in the inflamed lungs.