Abstract
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.
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Audi, S. H., G. S. Krenz, J. H. Linehan, D. A. Rickaby, and C. A. Dawson. Pulmonary capillary transport function from flow-limited indicators.J. Appl. Physiol. 77:332–351, 1994.
Audi, S. H., J. H. Linehan, G. S. Krenz, C. A. Dawson, S. B. Ahlf, and D. L. Roerig. Estimation of the pulmonary capillary transport function in isolated rabbit lungs.J. Appl. Physiol. 78:1004–1014, 1995.
Bassingthwaighte, J. B., and M. Chaloupka. Sensitivity functions in the estimation of parameters of cellular exchange.Fed. Proc. 43:180–184, 1984.
Bronikowski, T. A., C. A. Dawson, and J. H. Linehan. On indicator dilution and perfusion heterogeneity: A stochastic model.Math Biosci. 83:199–225, 1987.
Bronikowski, T. A., C. A. Dawson, J. H. Linehan, and D. A. Rickaby. A mathematical model of indicator extraction by the pulmonary endothelium via saturation kinetics.Math. Biosci. 61:237–266, 1982.
Chinard, F. P., The permeability characteristics of the pulmonary blood-gas barrier. In:Advances in Respiratory Physiology, edited by C. G. Caro Baltimore Williams and Wilkins, 1966, pp. 106–147.
Crone, C. Permeability of capillaries in various organs as determined by use of the “indicator diffusion” method.Acta Physiol. Scand. 48:292–305, 1963.
Dupuis, J., C. A. Goresky, C. Juneau, A. Calderone, J. L. Rouleau, C. P. Rose, and S. Goresky. Use of norepinephrine uptake to measure lung capillary recruitment with exercise.J. Appl. Physiol. 68:700–713, 1990.
Effros, R. M., C. Murphy, K. Ozker, and A. Hacker. Kinetics of urea exchange in air-filled and fluid-filled rat lungs.Am. J. Physiol. 263:L619-L626, 1992.
Goresky C. A. Initial distribution and rate of uptake of sulfobromophthalein in the liver.Am. J. Physiol. 207:13–26, 1964.
Goresky, C. A., W. H. Ziegler, and G. G. Bach. Capillary permeability, barrier-limited and flow-limited distribution.Circ. Res. 27:739–764, 1970.
Harris, T. R., K. L. Brigham, and R. D. Rowlett. Pressure, serotonin, and histamine effects on multiple-indicator curves in sheep.J. Appl. Physiol. 44:245–253, 1978.
Harris, T. R., and K. L. Brigham. The exchange of small molecules as a measure of normal and abnormal lung microvascular function.Ann. N.Y. Acad. Sci. 417–434, 1982.
Harris, T. R., C. M. Waters, and F. R. Haselton. Use of scaling theory to relate measurements of lung endothelial barrier permeability.J. Appl. Physiol. 77:2496–2505, 1994.
Haselton, F. R., R. E. Parker, R. J. Roselli, and T. R. Harris. Analysis of lung multiple indicator data with an effective diffusivity model of capillary exchange.J. Appl. Physiol. 57:98–109, 1984.
Jacquez, J. A., and T. Perry. Parameter estimation: Local identifiability of parameters.Am. J. Physiol. 258:E727-E736, 1990.
König, M. F., J. M. Lucocq, and E. R. Weibel. Demonstration of pulmonary vascular perfusion by electron and light microscopy.J. Appl. Physiol. 75:1877–1883, 1993.
Lassen, N. A., and C. Crone. The extraction fraction of a capillary bed to hydrophilic molecules: Theoretical considerations regarding the single injection technique with a discussion of the role of diffusion between laminar streams (Taylor's effect). InCapillary Permeability, edited by C. Crone and N. A. Lassen. Copenhagen: Munksgaard, 1970, pp. 48–59.
Lassen, N. A., J. Trap-Jensen, S. C. Alexander, J. Olesen, and O. B. Paulson. Blood-brain barrier studies in man using the double-indicator method.Am. J. Physiol. 220:1627–1633, 1971.
Levin, M., J. Kuikka, and J. B. Bassingthwaighte. Sensitivity analysis of time-distributed parameters for a coronary circulation model.Med. Prog. Technol. 7:119–124, 1980.
Linehan, J. H., T. A. Bronikowski, and C. A. Dawson. Kinetics of uptake and metabolism by endothelial cells from indicator dilution data.Ann Biomed. Eng. 15:201–215, 1987.
Nelin, L. D., D. L. Roerig, D. A. Rickaby, J. H. Linehan, and C. A. Dawson. Influence of flow on pulmonary vascular surface area inferred from blue dextran efflux data.J. Appl. Physiol. 72:874–880, 1992.
Overholser, K. A., N. A. Lamangino, R. E. Parker, N. A. Pou, and T. R. Harris. Pulmonary vascular resistance distribution and recruitment of microvascular surface area.J. Appl. Physiol. 77:845–855, 1994.
Peterson B. T., T. R. Harris, and K. L. Brigham. Comparison of sodium and urea as indicators of pulmonary vascular permeability.Exp. Lung Res. 4:79–92, 1983.
Polefka, T. G., R. A. Garrick, W. R. Redwood, N. I. Swislocki, and F. P. Chinard. Solute-excluded volumes near the Novikoff cell surface.Am. J. Physiol. 247:C350-C356, 1984.
Roerig, D. L., C. A. Dawson, S. B. Ahlf, R. D. Bongard, J. H. Linehan, and J. P. Kampine. Use of blue dextran for measuring changes in perfused vascular surface area in lungs.Am. J. Physiol. 262:H728-H733, 1992.
Sangren, W. C., and C. W. Sheppard. Mathematical derivation of the exchange of a labeled substance between a liquid flowing in a vessel and an external compartment.Bull. Math. Biophys. 15:387–394, 1953.
Sheppard, C. W.Basic Principles of the Tracer Method. New York: Wiley, 1962, pp. 195–198.
Snapper, J. R., T. R. Harris, and K. L. Brigham. Effect of changing lung mass on lung water and permeability-surface area in sheep.J. Appl. Physiol. 52:1591–1597, 1982.
Tancredi, R. G., and T. Yipintsoi: Interrelationships of flow, intravascular pressure, and tissue perfusion in the measurement of capillary permeability to sodium in isolated dog lung lobes.Circ. Res. 46:669–680, 1980.
Taylor, G. I. Dispersion of soluble matter in solvent flowing slowly through a tube.Proc. R. Soc. Lond. 219:186–203, 1953.
Yipintsoi, T. Single-passage extraction and permeability estimation of sodium in normal dog lungs.Circ. Res. 39: 523–531, 1976.
Zelter, M., A. Lipavsky J. M. Hoeffel, and J. F. Murray. Effect of lung injuries on [14C]urea permeability-surface area product in dogs.J. Appl. Physiol. 45:1512–1520, 1984.
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Audi, S.H., Dawson, C.A., Linehan, J.H. et al. An interpretation of14C-urea and14C-primidone extraction in isolated rabbit lungs. Ann Biomed Eng 24, 337–351 (1996). https://doi.org/10.1007/BF02660884
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DOI: https://doi.org/10.1007/BF02660884