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Green's Function Methods for Analysis of Oxygen Delivery to Tissue by Microvascular Networks

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Abstract

Delivery of oxygen to tissue is an essential function of the circulatory system. The distance that oxygen can diffuse into oxygen-consuming tissue is small, and so tissue oxygenation is critically dependent on the spatial arrangement of microvessels in tissue. Theoretical methods have been developed to simulate the spatial distribution of oxygen levels in tissue surrounding a network of microvessels. Here, numerical methods based on a Green's function approach are presented, for realistic three-dimensional network geometries derived from observations of skeletal muscle, brain, and tumor tissues. Relative to finite-difference methods, the Green's function approach reduces the number of unknowns in the numerical formulation and allows rapid computations even for complex vascular geometries. Generally, the boundary conditions on the exterior of the computational domain are not known. Imposition of a no-flux boundary condition can lead to exaggerated estimates of the extent of hypoxia in the tissue region. A new version of the method is described that avoids this problem and can be applied to arbitrarily shaped tissue domains.

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REFERENCES

  1. Beard, D. A. Computational framework for generating transport models from databases of microvascular anatomy. Ann. Biomed. Eng 29: 837–843, 2001.

    Google Scholar 

  2. Beard, D. A., and J. B. Bassingthwaighte. Modeling advection and diffusion of oxygen in complex vascular networks. Ann. Biomed. Eng 29: 298–310, 2001.

    Google Scholar 

  3. Beard, D. A., K. A. Schenkman, and E. O. Feigl. Myocardial oxygenation in isolated hearts predicted by an anatomically real-istic microvascular transport model. Am.J.Physiol.Heart.Circ. Physiol. 285: H1826–H1836, 2003.

    Google Scholar 

  4. Bentley, T. B., H. Meng, and R. N. Pittman. Temperature de-pendence of oxygen diffusion and consumption in mammalian striated muscle. Am. J. Physiol. 264: H1825–H1830, 1993.

    Google Scholar 

  5. Brizel, D. M., B. Klitzman, J. M. Cook, J. Edwards, G. Rosner, and M. W. Dewhirst. A comparison of tumor and normal tissue microvascular hematocrits and red cell fluxes in a rat window chamber model. Int. J. Radiat. Oncol. Biol. Phys. 25: 269–276, 1993.

    Google Scholar 

  6. Chi, O. Z., H. M. Wei, J. Tse, S. L. Klein, and H. R. Weiss. Cere-bral microregional oxygen balance during chronic versus acute hypertension in middle cerebral artery occluded rats. Anesth. Analg. 82: 587–592, 1996.

    Google Scholar 

  7. Dewhirst, M. W., E. T. Ong, B. Klitzman, T. W. Secomb, R. Z. Vinuya, R. Dodge, D. Brizel, and J. F. Gross. Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. Radiat. Res. 130: 171–182, 1992.

    Google Scholar 

  8. Duling, B. R., and R. M. Berne. Longitudinal gradients in peri-arteriolar oxygen tension. A possible mechanism for the partic-ipation of oxygen in local regulation of blood flow. Circ. Res. 27: 669–678, 1970.

    Google Scholar 

  9. Fletcher, J. E. On facilitated oxygen diffusion in muscle tissues. Biophys. J. 29: 437–458, 1980.

    Google Scholar 

  10. Goldman, D., and A. S. Popel. A computational study of the ef-fect of capillary network anastomoses and tortuosity on oxygen transport. J. Theor. Biol. 206: 181–194, 2000.

    Google Scholar 

  11. Goldman, D., and A. S. Popel. A computational study of the ef-fect of vasomotion on oxygen transport from capillary networks. J. Theor. Biol. 209: 189–199, 2001.

    Google Scholar 

  12. Gray, L. H., and J. M. Steadman. Determination of the oxy-haemoglobin dissociation curves for mouse and rat blood. J. Physiol 175: 161–171, 1964.

    Google Scholar 

  13. Groebe, K. A versatile model of steady state O2 supply to tis-sue. Application to skeletal muscle. Biophys. J. 57: 485–498, 1990.

    Google Scholar 

  14. Hellums, J. D. The resistance to oxygen transport in the capil-laries relative to that in the surrounding tissue. Microvasc. Res. 13: 131–136, 1977.

    Google Scholar 

  15. Hellums, J. D., P. K. Nair, N. S. Huang, and N. Ohshima. Simu-lation of intraluminal gas transport processes in the microcircu-lation. Ann. Biomed. Eng. 24: 1–24, 1996.

    Google Scholar 

  16. Hoofd, L. Updating the Krogh model—assumptions and exten-sions. In: Oxygen Transport in Biological Systems: Modelling of Pathways from Environment to Cell, edited by S., Egginton and H. F. Ross. Cambridge University Press, 1992, pp. 197–229.

  17. Hoofd, L., J. Olders, and Z. Turek. Oxygen pressures calculated in a tissue volume with parallel capillaries. Adv. Exp. Med. Biol. 277: 21–29, 1990.

    Google Scholar 

  18. Hoofd, L., Z. Turek, K. Kubat, B. E. Ringnalda, and S. Kazda. Variability of intercapillary distance estimated on histological sections of rat heart. Adv. Exp. Med. Biol. 191: 239–247, 1985.

    Google Scholar 

  19. Hsu, R., and T. W. Secomb. A Green's function method for analysis of oxygen delivery to tissue by microvascular networks. Math. Biosci. 96: 61–78, 1989.

    Google Scholar 

  20. Kellogg, O. D. Foundations of Potential Theory. New York: Dover, 1953.

  21. Kimura, H., R. D. Braun, E. T. Ong, R. Hsu, T. W. Secomb, D. Papahadjopoulos, K. Hong, and M. W. Dewhirst. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res. 56: 5522–5528, 1996.

    Google Scholar 

  22. Klitzman, B., A. S. Popel, and B. R. Duling. Oxygen transport in resting and contracting hamster cremaster muscles: Experi-mental and theoretical microvascular studies. Microvasc. Res. 25: 108–131, 1983.

    Google Scholar 

  23. Krogh, A. The number and the distribution of capillaries in muscle with the calculation of the oxygen pressure necessary for supplying the tissue. J. Physiol. (Lond.) 52: 409–515, 1919.

    Google Scholar 

  24. Lo, A., A. J. Fuglevand, and T. W. Secomb. Oxygen delivery to skeletal muscle fibers: Effects of microvascular unit structure and control mechanisms. Am. J. Physiol. Heart Circ. Physiol. 285: H955–H963, 2003.

    Google Scholar 

  25. Middleman, S. Transport Phenomena in the Cardiovascular Sys-tem. New York: John Wiley, 1972.

    Google Scholar 

  26. Motti, E. D., H. G. Imhof, and M. G. Yasargil. The terminal vascular bed in the superficial cortex of the rat. An SEM study of corrosion casts. J. Neurosurg. 65: 834–846, 1986.

    Google Scholar 

  27. Popel, A. S. Theory of oxygen transport to tissue. Crit. Rev. Biomed. Eng. 17: 257–321, 1989.

    Google Scholar 

  28. Pozrikidis, C., and D. A. Farrow. A model of fluid flow in solid tumors. Ann. Biomed. Eng. 31: 181–194, 2003.

    Google Scholar 

  29. Pries, A. R., K. Ley, M. Claassen, and P. Gaehtgens. Red cell dis-tribution at microvascular bifurcations. Microvasc. Res. 38: 81–101, 1989.

    Google Scholar 

  30. Secomb, T. W., and R. Hsu. Analysis of oxygen delivery to tissue by microvascular networks. Adv. Exp. Med. Biol. 222: 95–103, 1988.

    Google Scholar 

  31. Secomb, T. W., and R. Hsu. Simulation of O2 transport in skeletal muscle: Diffusive exchange between arterioles and capillaries. Am. J. Physiol. 267: H1214–H1221, 1994.

    Google Scholar 

  32. Secomb, T. W., R. Hsu, N. B. Beamer, and B. M. Coull. The-oretical simulation of oxygen transport to brain by networks of microvessels: Effects of oxygen supply and demand on tissue hypoxia. Microcirculation 7: 237–247, 2000.

    Google Scholar 

  33. Secomb, T. W., R. Hsu, R. D. Braun, J. R. Ross, J. F. Gross, and M. W. Dewhirst. Theoretical simulation of oxygen transport to tumors by three-dimensional networks of microvessels. Adv. Exp. Med. Biol. 454: 629–634, 1998.

    Google Scholar 

  34. Secomb, T. W., R. Hsu, M. W. Dewhirst, B. Klitzman, and J. F. Gross. Analysis of oxygen transport to tumor tissue by microvas-cular networks. Int. J. Radiat. Oncol. Biol. Phys. 25: 481–489, 1993.

    Google Scholar 

  35. Unthank, J. L., J. M. Lash, J. C. Nixon, R. A. Sidner, and H. G. Bohlen. Evaluation of carbocyanine-labeled erythrocytes for microvascular measurements. Microvasc. Res. 45: 193–210, 1993.

    Google Scholar 

  36. Weiss, R. Parameter-Free Iterative Linear Solvers. Berlin: Akademie Verlag GmbH, 1996.

    Google Scholar 

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Secomb, T.W., Hsu, R., Park, E.Y.H. et al. Green's Function Methods for Analysis of Oxygen Delivery to Tissue by Microvascular Networks. Annals of Biomedical Engineering 32, 1519–1529 (2004). https://doi.org/10.1114/B:ABME.0000049036.08817.44

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