Abstract
We have developed a new model describing the relationship between plasma and red cell tracers flowing through the lung. The model is the result of an analysis of the transport of radiolabeled plasma albumin between two flowing phases and shows that differences between red cell and plasma tracer curves are related to microvascular hematocrit. The model was tested in an isolated, blood-perfused dog lung preparation in which we injected51Cr-labeled red cells and125I-labeled plasma albumin into the pulmonary artery. From the tracer concentration-time curves at the venous outflow, we calculatedh r, the ratio of microvascular hematocrit to large-vessel hematocrit. In 18 baseline experiments,h r=0.92±0.01 (mn±sem) at a blood flow rate of 10.7±0.3 ml s−1. We determined the effects of (a) glass bead embolization, (b) alloxan, and (c) lobe ligation onh r. Embolization attenuated the separation between plasma and red cells (increasedh r), probably as a consequence of passive vasodilation. Alloxan enhanced separation of plasma and red cells (decreasedh r), possibly as a result of arteriolar vasoconstriction. Ligation of a fraction of the perfused tissue at constant flow did not cause significant change inh r in the remaining perfused tissue. The model assumes that large-vessel transit times are uniform and that all dispersion occurs in the microvasculature. A theoretical analysis apportioning dispersion between large and small vessels disclosed that the error associated with these assumptions is likely to be less than 15% of the measuredh r. We conclude from this study that the microvascular hematocrit model describes experimental plasma and red cell curves. The results imply thath r can be readily deduced from tagged red cells and plasma and can be accounted for in calculating permeability-surface area in diffusing tracer experiments.
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Literature
Aviado, D. M. and C. F. Schmidt. 1957. Pathogenesis of pulmonary edema by alloxan.Circ. Res. 5, 180–186.
Baker, C. H., E. F. Sutton and D. L. Davis. 1980. Microvessel mean transit time and blood flow velocity of sulfhemoglobin-RBC.Am. J. Physiol. 238, H745-H749.
Baker, C. H., E. F. Wilmoth and D. L. Davis. 1986. Reduced RBC versus plasma microvascular flow due to endotoxin.Circ. Shock 20, 127–139.
Bradley, J. D. 1988. Ph.D. Dissertation, Department of Biomedical Engineering, Vanderbilt University.
Bradley, J. D., R. E. Parker, K. A. Overholser and T. R. Harris. 1987. Capillary filtration coefficient (Kfc) and permeability surface area (PS) in the isolated dog Lung (abs).Fed. Proc. 46, 1423.
Brigham, K. L., W. C. Woolverton and N. C. Staub. 1975. Effects of changing hemodynamics on the extra plasma space in the lungs of sheep.Microvascular Res. 10, 352–359.
Capen, R. L., W. L. Hanson, L. P. Latham, C. A. Dawson and W. W. Wagner, Jr. 1990. Distribution of pulmonary capillary transit times in recruited networks.J. appl. Physiol. 69, 473–478.
Capen, R. L., L. P. Latham and W. W. Wagner, Jr. 1987. Comparison of direct and indirect measurements of pulmonary capillary transit times.J. appl. Physiol. 62, 1150–1154.
Cokelet, G. R. 1974. Experimental determination of the average, hematocrit of blood flowing in a vessel.Microvas. Res. 7, 382–384.
Duling, B. R. and C. Desjardins. 1987. Capillary hematocrit—what does it mean?NIPS 2, 66–69.
Effros, R. M. 1984. Pulmonary microcirculation and exchange. InHandbook of Physiology. Sect IV. The Cardiovascular System, Part 2. Bethesda, MD: American Physiology Society.
Gaehtgens, P. 1980. Flow of blood through narrow capillaries: rheological mechanisms determining capillary hematocrit and apparent viscosity.Biorheology 17, 183–189.
Gibson, J. G., A. M. Seligman, W. C. Peacock, J. C. Aub, J. Fine and R. D. Evans. 1946. The distribution of red cells and plasma in large and minute vessels of the dog, determined by radioactive isotopes of iron and iodine.J. Clin. Inves. 25, 848–857.
Goresky, C. A., W. H. Ziegler and G. G. Bach. 1978. Capillary exchange modeling: barrier—limited and flow-limited distribution.Circ. Res. 27, 739–764.
Harris, T. R., R. J. Roselli, C. R. Maurer, R. E. Parker and N. A. Pou. 1987. Comparison of labeled propanediol and urea as markers of lung vascular Injury.J. Appl. Physiol. 62, 1852–1859.
Hintze, J. L. 1987.Number Cruncher Statistical System. Kaysville, UT: Jerry L. Hintze.
Hogg, J. C., B. A. Martin, S. Lee and T. McLean. 1985. Regional differences in erythrocyte transit in normal lungs.J. appl. Physiol. 59, 1266–1271.
Hogg, J. C., T. McLean, B. A. Martin and B. Wiggs. 1988. Erythrocyte transit and neutrophil concentration in the dog lung.J. appl. Physiol.,65, 1217–1225.
Lee, J. S., L. P. Lee, M. V. Evans and L. Gamas. 1985. A density method to quantify pulmonary microvascular hematocrit.Microvas. Res. 30, 222–234.
Lipowsky, H. H. S., Usami and S. Chien. 1980.In vivo measurements of “apparent viscosity” and microvessel hematocrit in the mesentery of the cat.Microvas. Res. 19, 297–319.
Marquardt, D. W. 1963. An algorithm for least-squares estimation of nonlinear parameters.J. Soc. Ind. Appl. Math. 11, 431.
Ohkuda, K., K. Nakahara, W. J. Weidner, A. Binder and N. C. Staub. 1978. Lung fluid exchange after uneven pulmonary artery obstruction in sheep.Circ. Res. 43, 152–161.
Parker, J. C., J. Ryan and A. E. Taylor. 1984. Plasma-lymph albumin kinetics, total lymph flow and tissue hematocrit in normally hydrated dog lungs.Microvas. Res. 25, 848–857.
Parker, R. E., J. D. Bradley, N. A. Pou, R. J. Roselli and K. A. Overholser. 1988. Effects of glass bead embolization on pulmonary occlusion pressures and filtration coefficient in isolated dog lung lobes (abs).FASEB Jl 2, A1503.
Pries, A. R. and P. Gaehtgens. 1989. Dispersion of blood cell flow in microvascular networks. InMicrovascular Mechanics: Hemodynamics of Systemic and Pulmonary Microcirculation, J. S. Lee and T. C. Skalak (Eds), pp. 39–49. New York: Springer.
Pries, A. R., K. Ley and P. Gaehtgens. 1986. Generalization of the fahraeus principle for microvessel networks.Am. J. Physiol. 251, H1324-H1332.
Rose, C. P. and C. A. Goresky. 1976. Vasomotor control of capillary transit time heterogeneity in the canine coronary circulation.Circ. Res. 39, 541–555.
Roselli, R. J. and T. R. Harris. 1976. A four-phase model of capillary tracer exchange.Ann. biomed. Engr 7, 203–238.
Rowlett, R. D. and T. R. Harris. 1976. A comparative study of organ models and numerical techniques for the evaluation of capillary permeability from multiple-indicator data.Math. Biosciences 29, 273–298.
Sarelius, I. H. and B. R. Duling. 1982. Direct measurement of microvessel hematocrit, red cell flux, velocity and transit time.Am. J. Physiol. 243, H1018-H1026.
Snedecor, G. W. and W. G. Cochran. 1967.Statistical Methods, 6th Edition. Ames, IA: The University of Iowa Press.
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An erratum to this article is available at http://dx.doi.org/10.1007/BF02458300.
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Overholser, K.A., Lomangino, N.A., Harris, T.R. et al. Deduction of pulmonary microvascular hematocrit from indicator dilution curves. Bltn Mathcal Biology 56, 225–247 (1994). https://doi.org/10.1007/BF02460641
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DOI: https://doi.org/10.1007/BF02460641