An interpretation of14C-urea and14C-primidone extraction in isolated rabbit lungs
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We measured the venous concentration versus time curves of14C-urea and14C-primidone after rapid bolus injections of a vascular reference indicator, fluorescein isothiocyanate dextran, and one of the two14C-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 the14C-urea and14C-primidone outflow curves using the Crone model, the estimates of thePS product were directly proportional toF. However, the fractional change in thePS with flow was different for the two indicators. We also estimated thePS from the same14C-urea and14C-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 either14C-urea or14C-primidone at all four flows studied with one flow-independentPS for each indicator. The ability of the new model to explain the14C-urea and14C-primidone data with no flow-dependent change inPS suggests that a change inPS withF estimated using other models such as the Crone model is not sufficient evidence for capillary surface area recruitment.
KeywordsPermeability-surface area product Mathematical model Crone model Recruitment Lung vascular volume Sensitivity analysis
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