Advertisement

The Roles of Small Molecules as Probes of Endothelial Barrier Function in the Lung: Novel Measurement Methods and Molecular Probes

  • Thomas R. Harris
Conference paper

Abstract

Dysfunction of the barrier properties of endothelial cells is implicated in a number of vascular diseases. One of the more prominent problems is the edema of the lungs seen with Adult Respiratory Distress Syndrome (1,2). Fluid accumulates in the lungs of such patients even though pulmonary pressures are relatively normal. Experimental and patient studies suggest that the primary defect is an increased permeability of the lung vascular capillaries to fluid and macromolecules (3,4,5,6). A variety of methods have been used to assess such malfunctions in experimental animal models of ARDS and in patients. These range from straightforward measurements of lung water by post mortem desiccation and weighing to experimental measurement of lung lymph flow and analysis of protein content as compared to plasma protein concentration.

Keywords

Adult Respiratory Distress Syndrome Extravascular Lung Water Indicator Dilution Plasma Protein Concentration Permeability Surface Area Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Staub, N.C., Pathophysiology of Pulmonary Edema. In: Edema, 30:719–46, Staub and Taylor, eds., New York, Raven Press, 1984.Google Scholar
  2. 2.
    Bernard, G.R., and Brigham, K.L., Pulmonary Edema: Pathophysiologic mechanisms and new approaches to therapy. Chest, 89: 594–600, 1986.CrossRefGoogle Scholar
  3. 3.
    Esbenshade, A.M., Newman, J.H., Lams, P.H., Jolles, H., and Brigham, K. L. Respiratory failure after endotoxin infusion in sheep: Lung mechanics and lung fluid balance. J. Appl. Physiol. 53:967–76, 1979.Google Scholar
  4. 4.
    Bradley, J.D., Roselli, R.J., Parker, R.E., and Harris, T.R. Effects of endotoxemia on the sheep lung microvascular membrane: A two-pore theory. J. Appl. Physiol. 64:2675–2683, 1988.Google Scholar
  5. 5.
    Rinaldo, J.E. Borovetz, H.S., Mancini, M.C., Hardesty, R.L., Griffith, B.P. Assessment of lung injury in the adult respiratory distress syndrome using multiple indicator dilution curves. Am. Rev. Respir. Dis. 133(6): 1006–10, 1986.Google Scholar
  6. 6.
    Harris, T.R., Bernard, G.R., Brigham, K.L., Higgins, S.B., Rinaldo, J.E., Borovetz, H.S., Sibbald, W.J., Kariman, K., Sprung, C.L. Lung microvascular transport properties measured by multiple indicator dilution methods in ARDS patients: A comparison between patients reversing respiratory failure and those failing to reverse. Am. Rev. Resp. Dis. 141:272–280, 1990.Google Scholar
  7. 7.
    Byrne, K., Sugerman, H.J. Experimental and clinical assessment of lung injury by measurement of extravascular lung water and transcapillary protein flux in ARDS: a review of current techniques. J. Surg. Res. 44:185–203, 1988.CrossRefGoogle Scholar
  8. 8.
    Mintun, Mark A., Dennis, D.R., Welch, MJ., Mathias, C.J., Schuster, D.P. Measures of pulmonary vascular permeability with PET and Gallium-68 transferrin. J. Nucl. Med. 28:1704–1716, 1987.Google Scholar
  9. 9.
    Roselli, RJ. and Riddle, W.R. Analysis of non-invasive microvascular macromolecular transport measurements in the lung. J. Appl. Physiol. 67:2343–2350, 1989.Google Scholar
  10. 10.
    Chinard, F.P. Estimation of extravascular lung water by indicator-dilution techniques. Circ. Res. 37:137–145, 1975.Google Scholar
  11. 11.
    Harris, T.R., Brigham, K.L. The exchange of small molecules as a measure of normal and abnormal lung microvascular function. Ann. N.Y. Acad. Sci. 384:417–434, 1982.CrossRefGoogle Scholar
  12. 12.
    Bassingthwaighte, J.B., Goresky, C.A. Modeling in the analysis of solute and water exchange in the microvasculature. Handbook of Physiology - The Cardiovascular System IV, American Physiological Society, 1985.Google Scholar
  13. 13.
    Harris, T.R., Bernard, G.R., Roselli, RJ., Maurer, C.R., Pou, N.A. Extravascular lung water by infrared and other measures. Proc. Ann. Conf. Engr. Med. Biol. 27:77, 1985.Google Scholar
  14. 14.
    Lewis, F.R., Elings, V.B., Hill, S.L., Christensen, J.M. The measurement of extravascular lung water by thermal-green dye indicator dilution. Ann: N.Y. Acad. Sci. 384:394–410, 1982.CrossRefGoogle Scholar
  15. 15.
    Rickaby, D.A., Linehan, J.H., Bronikowski, T.A., Dawson, C.A. Kinetics of serotonin uptake in the dog lung. J. Appl. Physiol. 51:405–414, 1981.Google Scholar
  16. 16.
    Syrota, A., Girauld, M., Pocidalo, J-J., Yudilevich, D.L. Endothelial uptake of amino acids, sugars, lipids, and prostaglandins in rat lung. Am. J. Physiol. 243: C20–C26, 1982.Google Scholar
  17. 17.
    Harris, T.R., Rowlett, R.D., Brigham, K.L. The computation of pulmonary capillary permeability from multiple-indicator data: The effects of increased capillary pressure and alloxan treatment. Microvascular Research 12:177–196, 1976.CrossRefGoogle Scholar
  18. 18.
    Harris, T.R., Brigham, K.L., Rowlett, R.D. Pressure, serotonin and histamine effects on lung multiple-indicator curves in sheep. J. Appl. Physiol. 44:245–253, 1978.Google Scholar
  19. 19.
    Zelter, M., Lipavsky, D., Hoeffel, J.M., Murray, J.F. Effect of lung injuries on 14C-urea permeability surface area product in dogs. J. Appl. Physiol. 56:1512–1520, 1984.Google Scholar
  20. 20.
    Brigham, K.L., Snell, J.D., Harris, T.R., Marshall, S., Haynes, J., Bowers, R.E., Perry, J. Indicator dilution lung water and vascular permeability in humans: Effects of pulmonary vascular pressure. Circ. Res. 44:523–530,1979.Google Scholar
  21. 21.
    Brigham, KL., Kariman, K., Harris, T.R., Snapper, J.R., Young, S.L. Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema. J. Clin. Invest. 72:339–349, 1983.CrossRefGoogle Scholar
  22. 22.
    Renkin, E.M. Transport of potassium-42 from the blood to tissue in isolated mammalian skeletal muscles. Am. J. Physiol. 197:1209–10, 1959.Google Scholar
  23. 23.
    Crone, C. The permeability of capillaries in various organs determined by use of the “indicator diffusion” method. Acta Physiol. Scand. 58:292–305, 1963.CrossRefGoogle Scholar
  24. 24.
    Olson, L.E., Pou, A., Harris, T.R. Measurements of amphipatic and hydrophilic indicator-dilution tracers in the lung provide a surface area independent assessment of permeability changes. FASEB J. 3: A1140, 1989.Google Scholar
  25. 25.
    Basset, G., Martel, G., Bouchonnet, F., Marsac, J., Sutton, J., Botter, F., Capitini, R. Simultaneous detection of deuterium oxide and indocyanine green in flowing blood. J. Appl. Physiol. 50:1367–1371, 1981.Google Scholar
  26. 26.
    Neufeld, G. et al. Proceedings, 2nd Int. Symposium on Computing in Anesthesia and Intensive Care, Rotterdam, 1983.Google Scholar
  27. 27.
    Harris, T.R., Roselli, RJ., Maurer, C.R., Parker, R.E., Pou, N.A. Comparison of labelled propanediol and urea as markers on lung vascular injury. J. Appl. Physiol. 62:1852–1859, 1987.Google Scholar
  28. 28.
    Galloway, R.L., Jr., Staton, D.J., Harris, T.R. The optical measurement of 1,2-propanediol for the determination of lung capillary permeability surface area. IEEE Trans. on Biomed. Engr. 36:591–596,1989.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1990

Authors and Affiliations

  • Thomas R. Harris
    • 1
  1. 1.Departments of Biomedical Engineering and MedicineVanderbilt UniversityNashvilleUSA

Personalised recommendations