An interpretation of14C-urea and14C-primidone extraction in isolated rabbit lungs

Abstract

We measured the venous concentration versus time curves of 14C-urea and 14C-primidone after rapid bolus injections of a vascular reference indicator, fluorescein isothiocyanate dextran, and one of the two 14C-labeled indicators in isolated rabbit lungs perfused with Krebs-Ringer bicarbonate solution containing 4.5% bovine serum albumin at flow rates (F) of 6.67, 3.33, 1.67, and 0.83 ml/sec and with nearly constant microvascular pressure and total lung vascular volume. When we calculated the permeability-surface area product, PS, from the 14C-urea and 14C-primidone outflow curves using the Crone model, the estimates of the PS product were directly proportional to F. However, the fractional change in the PS with flow was different for the two indicators. We also estimated the PS from the same 14C-urea and 14C-primidone data using an alternative model that includes perfusion heterogeneity, estimated in a previous study, and flow-limited and barrier-limited extravascular volumes accessible to both urea and primidone. This model was able to fit the outflow curves of either 14C-urea or 14C-primidone at all four flows studied with one flow-independent PS for each indicator. The ability of the new model to explain the 14C-urea and 14C-primidone data with no flow-dependent change in PS suggests that a change in PS with F estimated using other models such as the Crone model is not sufficient for capillary surface area recruitment.

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

“…The experiments were performed by using an isolated rabbit lung preparation, as previously described (1,2,5). New Zealand White rabbits of either sex were given chlorpromazine hydrochloride (25 mg/kg im), followed by pentobarbital sodium (20-25 mg/kg) via an ear vein, and then were heparinized (1,200 IU/kg) and exsanguinated via a carotid artery catheter.…”

“…The pulmonary artery, vein, and trachea were cannulated, and a ligature was secured around the ventricles. The lungs were removed from the chest and attached to the perfusion system primed with a perfusate containing a PSS (in g/l: 0.35 KCl, 0.37 CaCl 2 ·2H 2 O, 0.29 MgSO 4 ·7H 2 O, 0.16 KH 2 PO 4 , 6.9 NaCl, 1 glucose, and 2.1 NaHCO 3 ) with 45 g/l of BSA (1,2,5). The perfusion system included a heated perfusate reservoir and a Master Flex roller pump, which pumped perfusate at a constant mean flow of 3.33 ml/s from the reservoir into the pulmonary artery, with the left atrial pressure set equal to atmospheric (pleural) pressure by adjusting the height of the venous outflow into the recirculation reservoir.…”

“…The 3 HOH was used to trace the perfused extravascular water volume and the [ 14 C]PEA, which is extracted by the endothelial cells (6,18), was used as an indicator of perfused endothelial surface. The MID experiments were carried out on isolated perfused rabbit lungs to facilitate control over a number of variables (1,2,4,5,16,28,29). Lung tissue properties were manipulated in several ways.…”

Advection and Diffusion of Substances in Biological Tissues With Complex Vascular Networks

“…For example, Audi et al 1,2 have noted that the Crone-Renkin model and other axially distributed descriptions of tracer transport may lead to variations in estimates of parameters (such as permeability) with flow. A comparison of the behavior of an alternative model (our three-dimensional network model) to that of axial-distributed models, provides new insight into this issue.…”

“…(1), which is derived in Appendix A, (1) Here, D is the extravascular intratissue radial molecular diffusion coefficient, R o is the outer radius of the effective extravascular Krogh cylinder, R i is the inner radius, L is the length of the tissue cylinder, and ρ is the density of the tissue in g ml −1 . Using D = 1 × 10 −5 cm 2 s −1 , ρ = 1.0 g ml −1 , R i = 3.5 μm, and R o = 15 μm, one obtains an estimate of PS=500 ml min −1 g −1 .…”