Skip to main content
Log in

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

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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.

    PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. Bassingthwaighte, J. B., and M. Chaloupka. Sensitivity functions in the estimation of parameters of cellular exchange.Fed. Proc. 43:180–184, 1984.

    Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    Google Scholar 

  7. Crone, C. Permeability of capillaries in various organs as determined by use of the “indicator diffusion” method.Acta Physiol. Scand. 48:292–305, 1963.

    Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. 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.

    PubMed  CAS  Google Scholar 

  10. Goresky C. A. Initial distribution and rate of uptake of sulfobromophthalein in the liver.Am. J. Physiol. 207:13–26, 1964.

    PubMed  CAS  Google Scholar 

  11. Goresky, C. A., W. H. Ziegler, and G. G. Bach. Capillary permeability, barrier-limited and flow-limited distribution.Circ. Res. 27:739–764, 1970.

    PubMed  CAS  Google Scholar 

  12. 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.

    PubMed  CAS  Google Scholar 

  13. 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.

  14. 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.

    PubMed  CAS  Google Scholar 

  15. 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.

    PubMed  CAS  Google Scholar 

  16. Jacquez, J. A., and T. Perry. Parameter estimation: Local identifiability of parameters.Am. J. Physiol. 258:E727-E736, 1990.

    PubMed  CAS  Google Scholar 

  17. 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.

    PubMed  Google Scholar 

  18. 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.

    Google Scholar 

  19. 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.

    PubMed  CAS  Google Scholar 

  20. 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.

    PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. 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.

    PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. 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.

    PubMed  CAS  Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. Sheppard, C. W.Basic Principles of the Tracer Method. New York: Wiley, 1962, pp. 195–198.

    Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. Taylor, G. I. Dispersion of soluble matter in solvent flowing slowly through a tube.Proc. R. Soc. Lond. 219:186–203, 1953.

    Article  CAS  Google Scholar 

  32. Yipintsoi, T. Single-passage extraction and permeability estimation of sodium in normal dog lungs.Circ. Res. 39: 523–531, 1976.

    PubMed  CAS  Google Scholar 

  33. 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.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02660884

Keywords

Navigation