An interpretation of ¹⁴C-urea and ¹⁴C-primidone extraction in isolated rabbit lungs

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 evidence for capillary surface area recruitment.