Estimation of the pulmonary capillary transport function in isolated rabbit lungs

Recently, we presented a method for estimating the pulmonary capillary volume and transport function based on the use of a reference indicator and two or more indicators that rapidly equilibrate (radially) with the tissue (i.e., the concentrations in the vascular and extravascular spaces at a given axial location are in equilibrium) during transit through the capillaries in a bolus-injection indicator dilution method (S. H. Audi, G. S. Krenz, J. H. Linehan, D. A. Rickaby, and C. A. Dawson. J. Appl. Physiol. 77:332-351, 1994). The objectives of the present study were 1) to determine whether [14C]diazepam and [3H]alfentanil equilibrate sufficiently rapidly between the vascular space and tissue and with sufficiently different pulmonary extra-vascular mean residence times to be used in a single bolus to estimate the pulmonary capillary volume and transport function using this method and 2) to estimate the pulmonary capillary volume and transit time distribution in isolated perfused rabbit lungs. Both [14C]diazepam and [3H]alfentanil were found to be rapidly equilibrating indicators by the criteria that, over a wide range of flow rates, their respective venous effluent concentration curves were nearly congruent on a time scale normalized to the lung mean transit time for the reference indicator (fluorescein isothiocyanate dextran). In addition, at a given plasma albumin concentration, [14C]diazepam had a significantly longer extravascular mean residence time than [3H]alfentanil, e.g., at 6% plasma albumin concentration, the extravascular mean residence time of [14C]diazepam was more than twice that of [3H]alfentanil. On average, the estimated pulmonary capillary volume for a 2.7-kg was approximately 4.2 ml or approximately 44% of the total pulmonary vascular volume (9.5 ml). The relative dispersion of the pulmonary capillary transport function of the rabbit was approximately 90%.