Abstract
Estimates of capillary tracer permeability calculated using multiple indicator data depend upon the particular model adopted to describe blood tissue exchange. The model proposed by Crone (1963) is appropriate when some of the injected tracer diffuses into the tissue but does not return appreciably to the bloodstream before data collection is terminated. Under these conditions extraction of tracer by the tissue depends on a single dimensionless parameter, αcap, defined as the ratio of capillary permeability surface area to water flow. The effects of finite red cell tracer permeability on the Crone model estimate of capillary permeability are examined in the present study. The results indicate that even when back diffusion from the extravascular space is negligible, significant errors in the Crone model estimate can be expected when capillary permeability is relatively high and the ratio of red cell to capillary permeability is less than unity. However, when an aliquot of blood is equilibrated with tracer prior to injection and the dimensionless capillary permeability is relatively low (i.e. αcap ≦ 0.25 for a haematocrit≦50%), the whole blood Crone model estimate of αcap will be within 10% of the actual value, irrespective of red cell permeability. Red cell-plasma exchange for commonly used tracer-organ combinations should not significantly affect Crone estimates of capillary permeability under normal physiological conditions, but may be important in low flow situations.
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Literature
Brigham, K. L., T. R. Harris, R. D. Rowlett and P. J. Owen. 1977. “Comparisons of14C-urea and3H-mannitol as Lung Vascular Permeability Indicators in Awake Sheep: Evidence Against Red Cell Urea Trapping”.Microvasc. Res.,13, 97–105.
— J. D. Snell, Jr., T. R. Harris, S. Marshall, J. Haynes, R. E. Bowels and J. Perry. 1979. “Indicator Dilution Lung Water and Vascular Permeability in Humans: Effects of Pulmonary Vascular Pressure”.Circulation Res.,44, 523–530.
Chinard, F. P., C. A. Goresky, T. Enns, M. F. Nolan, and W. House. 1965. “Trapping of Urea by Red Cells in the Kidney”.Am. J. Physiol.,209, 253–263.
Crone, C. 1963. “Permeability of Capillaries in Various Organs as Determined by Use of the Indicator Diffusion Method”.Acta physiol. scand.,58, 292–305.
Goresky, C. A., G. G. Bach and B. E. Nadeau. 1975. “Red Cell Carriage of Label: Its Limiting Effect on Exchange of Materials in the Liver”.Circulation Res. 36, 328–351.
—, R. F. P. Cronin and B. E. Wangel. 1969. “Indicator Dilution Measurements of Extravascular Water in the Lungs”.J. clin. Invest.,48, 487–501.
—, W. H. Ziegler and G. G. Bach. 1970. “Capillary Exchange Modeling: Barrier-limited and Flow-limited Distribution”.Circulation Res.,27, 739–764.
Guller, B., T. Yipintsoi, A. L. Orvis and J. B. Bassingthwaighte, 1975. “Myocardial Sodium Extraction at Varied Coronary Flows in the Dog”.Circulation Res.,37, 359–378.
Harris, T. R., R. D. Rowlett and K. L. Brigham. 1976. “The Identification of Pulmonary Capillary Permeability from Multiple Indicator Data. Effects of Increased Capillary Pressure and Alloxan Treatment in the Dog”.Microvasc. Res.,12, 177–196.
—, K. L. Brigham and R. D. Rowlett. 1978. “Pressure, Serotonin and Histamine Effects on Lung Multiple-Indicator Curves in Sheep”.J. appl. Physiol: Resp. Envir. Exercise Physiol.,44, 245–253.
Perl, W. 1975. “Red Cell Permeability Effect on the Mean Transit Time of an Indicator Transported Through an Organ by Red Cells and Plasma.”Circulation Res.,36, 352–357.
Roselli, R. J. and T. R. Harris, 1979a. A Four Phase Model of Capillary Tracer Exchange.Ann. biomed. Engng. 7, 203–228.
— and— 1979b. “The Effects of Red Cell and Tissue Exchange on the Evaluation of Capillary Permeability from Multiple Indicator Data.”Ann. biomed. Engng. 7, 239–281.
Sangren, W. C. and C. W. Sheppard. 1953. Mathematical Derivation of the Exchange of a Labeled Substance Between a Liquid in a Vessel and an External Compartment.”Bull. math. Biophys.,15, 387–394.
Yudilevich, D. L. and O. A. Alvarez, 1967. Water, Sodium, and Thiourea Transcapillary Diffusion in the Dog Heart.Am. J. Physiol.,213, 308–314.
Ziegler, W. H. and C. A. Goresky. 1971. “Transcapillary Exchange in the Working Left Ventricle of the Dog.Circulation Res.,29, 181–207.
Literature for Tables A-I and Table A-II
Alvarez, O. A. and D. L. Yudilevich. 1969. “Heart Capillary Permeability to Lipid-Insoluble Molecules.”J. Physiol.,202, 45–58.
Ballin, N., V. E. Kinsey, D. V. N. Reddy and I. McLean. 1966. “Turnover of Thiourea in the Aqueous Humors of the Rabbit Eye.”Investve. Ophth.,5, 391–397.
Brigham, K. L., S. L. Faulkner, R. D. Fisher and H. W. Bender. 1976. “Lung Water and Urea Indicator Dilution Studies in Cardiac Surgery Patients.”Circulation,53, 369–376.
—, T. R. Harris, R. D. Rowlett, and P. J. Owen. 1977. “Comparisons of14C-urea and3H-mannitol as Lung Vascular Permeability Indicators in Awake Sheep: Evidence Against Red Cell Trapping.”Microvasc. Res.,13, 97–105.
—, J. D. Snell, T. R. Harris, S. Marshall, J. Haynes, R. E. Bowers and J. Perry (1979) “Indicator Dilution Lung Water and Vascular Permeability in Humans: Effects of Pulmonary Vascular Pressure.”Circulation Res.,44, 523–530.
—, H. Sundell, T. R. Harris, Z. Catterton, I. Kovar and M. Stahlman. 1978. “Lung Water and Vascular Permeability in Sheep. Newborns Compared with Adults.”Circulation Res. 42, 851–855.
Chinard, F. P. 1970. “Permeability of the Pulmonary Blood-Gas Barrier.” InCapillary Permeability. Alfred Benzon Symposium 2. Ed. C. Crone and N. A. Lassen. pp. 605–613. New York: Academic Press.
Crone, C. 1963. “The Permeability of Capillaries in Various Organs as Determined by use of the ‘Indicator Diffusion’ Method.”Acta physiol. scand.,58, 292–305.
Crone, C. 1963. “Does ‘Restricted Diffusion’ Occur in Muscle Capillaries?.”Proc. Soc. exp. Biol. Med.,112, 443–455.
— 1965. “The Permeability of Brain Capillaries to Non-Electrolytes.”Acta physiol. scand.,64, 407–417.
Dawson, H. and K. Welch. 1971. “The Permeation of Several Materials into the Fluids of the Rabbits Brain.”J. Physiol., Lond.,218, 337–351.
Duran, W. N. 1977. “Effects of Muscle Contraction and of Adenosine on Capillary Transport and Microvascular Flow in Dog Skeletal Muscle.”Circulation Res.,41, 642–647.
Eichling, J. O., M. E. Raichle, R. L. Grubb, Jr., M. M. Ter-Pogossian. 1974. “Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey.”Circulation Res.,35, 358–364.
Garlick, D. G. 1970. “Factors Affecting the Transport of Extracellular Molecules in Skeletal Muscle.” InCapillary Permeability. Alfred Bengon Symposium 2. Ed. C. Crone and N. A. Lassen, pp. 228–238. New York: Academic Press.
Guller, B., T. Yipintsoi, A. L. Orvis and J. B. Bassingthwaighte. 1975. “Myocardial Sodium Extraction at Varied Coronary Flows in the Dog.”Circulation Res.,37, 359–378.
Harris, T. R., K. L. Brigham and R. D. Rowlett, 1978. “Pressure, Serotonin and Histamine Effects on Lung Multiple-Indicator Curves in Sheep.”J. appl. Physiol.: Resp. Envir. Exercise Physiol.,44, 245–253.
—, C. A. Gervin, D. Burks and P. Custer. 1978. “Effects of Coronary Flow Reduction on Capillary-Myocardial Exchange in Dogs.”Am. J. Physiol.,234, H679-H689.
—, R. D. Rowlett and K. L. Brigham, 1976. “The Identification of Pulmonary Capillary Permeability from Multiple Indicator Data. Effects of Increased Capillary Pressure and Alloxan Treatment in the Dog.”Microvasc. Res.,12, 177–196.
Jain, M. K..The Biomolecular Lipid Membrane: A System. New York: Van Nostrand Reinhold.
Jay, A. W. L. 1976. “Permeability of Individual Human Erythrocytes to Thiourea.”J. Physiol.,262, 447–458.
Kinsey, V. E., D. V. N. Reddy and B. A. Skrentny. 1960. “Intravascular Transport of14C-labeled Urea and the Influence of Diamox on its Rate of Accumulation in Aqueous Humors.”Am. J. Opthal.,50, 1130–1141.
Landis, E. M. and J. R. Pappenheimer. 1962. “Exchange of Substances Through the Capillary Walls.” InHandbook of Physiology, Circulation Vol. II Sect. 2, Ed. W. Hamilton and P. Dow, pp. 961–1034. Washington: American Physiological Society.
Laughlin, M. H. and J. N. Diana, 1975. “Myocardial Transcapillary Exchange in the Hypertrophied Heart of the Dog.”Am. J. Physiol.,229, 838–846.
Naccache, P. and R. I. Sha’afi 1973. “Patterns of Nonelectrolyte Permeability in Human Red Blood Cell Membrane.”J. gen. Physiol.,62, 714–736.
Normand, I. C. S., R. E. Oliver, E. C. R. Reynolds, L. B. Stang and K. Welch. 1971. “Permeability of Lung Capillaries and Alveoli to Non-Electrolytes in the Foetal Lamb.”J. Physiol., Lond.,219, 303–330.
Paaske, W. P. and P. Sjrsen. 1977. “Transcapillary Exchange of14C-Inulin by Free Diffusion in Channels of Fused Vesicles.”Acta physiol. scand. 100, 437–445.
Pappenheimer, J. R. 1953. “Passage of Molecules Through Capillary Walls.”Physiol. Rev.,33, 387–423.
Patlak, C. S. and J. D. Fenstermacher. 1975. “Measurements of Dog Blood-Brain Transfer Constants by Ventriculosternal Perfusion.”Am. J. Physiol.,229, 877–884.
Perl, W., F. Silverman, A. C. Delea and F. P. Chinard. 1976. “Permeability of Dog Lung Endothelium to Sodium, Diols, Amioles and Water.”Am. J. Physiol.,230, 1708–1721.
Prosser, C. L. 1973.Comparative Animal Physiology. 3rd Ed., Tables 1–2, p. 9. Philadelphia: Saunders.
Raichle, M. E., J. O. Eichling, M. G. Straatmann, M. J. Welch, K. B. Larson and M. M. Ter-Pogossian. 1976. “Blood-Brain Barrier Permeability of14C-labeled Alcohols and15O-labeled Water.”Am. J. Physiol.,230, 543–552.
Rapoport, S. I. 1976.Blood-Brain Barrier in Physiology and Medicine. pp. 87–128. & 207–323. New York: Raven Press.
Reddy, D. V. N. 1960. “Carbohydrate Transport and Diabetes.” InGlaucoma, pp. 115–136. Princeton: Josiah Macy Foundation.
Redwood, W. R., E. Rall and W. Perl. 1974. “Red Cell Membrane Permeability Deduced from Bulk Diffusion Coefficients.”J. gen. Physiol.,64, 706–729.
Renkin, E. M. 1955. “Effects of Blood Flow on Diffusion Kinetics in Isolated, Perfused Hindlimbs of Cats: A Double Circulation Hypothesis.”Am. J. Physiol.,183, 125–136.
Rose, C. P., C. A. Goresky and G. G. Bach. 1977. “The Capillary and Sarcolemmal Barriers in the Heart. An Exploration of Labeled Water Permeability.”Circulation Res.,41, 515–533.
Roselli, R. J. Unpublished data.
Saari, J. T. and J. S. Beck. 1975. “Hypotonic Haemolysis of Human Red Blood Cells: A Two Phase Process.”J. Membr. Biol.,23, 213–226.
Schaefer, D. E. and J. A. Johnson. 1964. “Permeability of Mammalian Heart Capillaries to Sucrose and Inulin.”Am. J. Physiol.,206, 985–991.
Trap-Jensen, J. and N. A. Lassen. 1970. “Capillary Permeability for Smaller Hydrophilic Tracers in Exercising Skeletal Muscle in Normal Man and in Patients with Long-Term Diabetes Mellitus.”Capillary Permeability. Alfred Benzon Symposium 2. Ed. C. Crone and N. A. Lassen, pp. 135–152. New York: Academic Press.
— and—. 1971. “Restricted Diffusion in Skeletal Muscle Capillaries in Man.”Am. J. Physiol.,220, 371–376.
Vargas, F. and J. A. Johnson. 1967. “Permeability of Rabbit Heart Capillaries to Nonelectrolytes.”Am. J. Physiol.,213, 87–93.
Wangensteen, O. D., L. E. Wittmers and J. A. Johnson. 1969. Permeability of the Mammalian Blood-Gas Barrier and its Components.Am. J. Physiol.,216, 719–727.
Whittam, R. 1964.Transport and Diffusion in Red Blood Cells. Table II p.53. Baltimore: Williams and Wilkins.
Yipintsoi, T. 1976. “Single-passage Extraction and Permeability Estimation of Sodium in Normal Dog Lungs.”Circulation Res.,39, 523–531.
—, R. Trancredi, D. Richmond and J. B. Bassingthwaighte. 1970. “Myocardial Extractions of Sucrose, Glucose, and Potassium. InCapillary Permeability. Alfred Benzon Symposium 2. Ed. C. Crone and N. A. Lassen, pp. 153–156. New York: Academic Press.
Yudilevich, D. L. and O. A. Alvarez. 1967. Water, Sodium, and Thiourea Transcapillary Diffusion in the Dog Heart.”Am. J. Physiol.,213, 308–314.
—, E. M. Renkin, O. A. Alvarez and J. Bravo. 1968. “Fractional Extraction and Transcapillary Exchange During Continuous and Instantaneous Tracer Administration.”Circulation Res. 23, 325–336.
Ziegler, W. H. and C. A. Goresky. 1971. “Transcapillary Exchange in the Working Left Ventrical of the Dog.”Circulation Res.,29, 181–207.
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Supported by Grant No. HL 19153 (SCOR in Pulmonary Vascular Diseases).
This work was done during Dr. Roselli’s tenure as an NHLBI Training Grant Fellow (NHLBI Training Grant No. 07123).
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Roselli, R.J. Effects of red cell permeability on transcapillary tracer transport: The case of negligible back diffusion. Bltn Mathcal Biology 42, 765–795 (1980). https://doi.org/10.1007/BF02461058
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DOI: https://doi.org/10.1007/BF02461058