Skip to main content
Log in

Mathematical evidence for flow-induced changes in myocardial oxygen consumption

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

Abstract

The objective of this investigation was to aid in the determination of the mechanism by which oxygen consumption changes in proportion to coronary perfusion pressure or coronary blood flow. A mathematical model of oxygen transport and consumption in the isolated-perfused heart was developed, based on data from an autoregulating, cell-free perfused, externally paced, isovolumic feline heart preparation. The model features the unique combination of Michaelis-Menten kinetics, and one-dimensional (axial) diffusion in radially well-mixed tissue. An adaptive finite-difference integration routine was used to solve the resulting third order stiff two-point boundary value problem. A simplex minimization was employed to determine the parameter values that minimized the squared difference between the model and the experimental data in terms of tissue PO2 distribution (histograms). Different cases of the model representing pressure-induced, flow-induced, and “magnified” flow effects were run. The flow-dependent oxygen consumption version of the model produced a histogram squared error 30% lower than the pressure-induced version and 5% lower than any other case. The model and a critical review of the literature indicate that a flow-related mechanism is responsible for this phenomenon. Evidence also demonstrates that the Michaelis-Menten kinetics constant is not constant for different oxygen tensions.

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. Abel, R.M.; Reis, R.L. Effects of coronary blood flow and perfusion pressure on left ventricular contractility in dogs. Circ. Res. 28:961–971; 1970.

    Google Scholar 

  2. Arnold, G.; Kosche, F.; Miessner, E.; Neitzert, A.; Lochner, W. The importance of the perfusion pressure in the coronary arteries for the contractility and the oxygen consumption of the heart. Pflugers Archiv. 299:339–356; 1968.

    CAS  Google Scholar 

  3. Arnold, G.; Morgenstern, C.; Lochner, W. The autoregulation of the heart work by the coronary perfusion pressure. Pflugers Archiv. 321:34–55; 1970.

    Article  CAS  PubMed  Google Scholar 

  4. Bacaner, M.B.; Lioy, F.; Visscher, M. Induced change in heart metabolism as a primary determinant of heart performance. Am. J. Physiol. 209(3):519–531; 1965.

    CAS  PubMed  Google Scholar 

  5. Bacaner, M.B.; Lioy, F.; Visscher, M. Coronary blood flow, oxygen delivery rate and cardiac performance. J. Physiol. 216:111–127; 1971.

    CAS  PubMed  Google Scholar 

  6. Bassingthwaighte, J.B.; Yipintsoi, T.; Harvey, R.B. Microvasculature of the dog left ventricular myocardium. Microvasc. Res. 7:229, 1974.

    Article  CAS  PubMed  Google Scholar 

  7. Berne, R.M.; Rubio, R. Coronary circulation. In: Berne, R.M.; Sperelakis, N. eds. Handbook of Physiology: The Cardiovascular System. Washington, D.C.: Am. Physiol. Soc., sect. 2, vol. I, Chapt. 25, 1980: pp. 873–952.

    Google Scholar 

  8. Cronk, J.W.; Schubert, R.W. Michaelis-Menten-like kinetics in the Krogh tissue cylinder. In: Bruley, D.F.; Bicher, H.I.; Reneau, D.D., eds. Oxygen transport to tissue-VI. New York: Plenum Press; 1985: pp. 499–510.

    Google Scholar 

  9. Daniell, H.B. Coronary flow alterations on myocardial contractility, oxygen extraction, and oxygen consumption. Am. J. Physiol. 225(5):1020–1025; 1973.

    CAS  PubMed  Google Scholar 

  10. Feigl, E.O. Coronary physiology. Physiol. Rev. 63(1):1–205; 1983.

    CAS  PubMed  Google Scholar 

  11. Fisher, V.J.; Martino, R.A.; Harris, R.S.; Kavaler, F. Coronary flow as an independent determinant of myocardial contractile force. Am. J. Physiol. 217(4):1127–1133; 1969.

    CAS  PubMed  Google Scholar 

  12. Fletcher, J.E. Mathematical modeling of the microcirculation. Math. Biosci. 38:159–202; 1978.

    Article  Google Scholar 

  13. Fletcher, J.E.; Schubert, R.W. Diffusional coupling in perfused capillary-tissue structures. In: Lübbers, D.W.; Acker, H.; Leniger-Follert, E., eds. Oxygen transport to tissue-VI. New York: Plenum Press; 1983.

    Google Scholar 

  14. Garfinkel, D.; Fegley, K.A. Fitting physiological models to data. Am. J. Physiol. 246:R641–650; 1984.

    CAS  PubMed  Google Scholar 

  15. Gladwell, I. A survey of subroutines for solving boundary value problems in ordinary differential equations. In: Gladwell, Sayers, eds. Computational techniques for ordinary differential equations. New York: Academic Press; 1980: pp. 273–303.

    Google Scholar 

  16. Gregg, D.E.. Regulation of the collateral and coronary circulation of the heart. Circulation. Oxford: Blackwell Scientific Publications; 1958.

    Google Scholar 

  17. Gregg, D.E.. Effect of coronary perfusion pressure or coronary flow on oxygen usage of the myocardium. Circ. Res. 13:497–500; 1963.

    CAS  PubMed  Google Scholar 

  18. Kahler, R.L.; Braunwald, E.; Kelminson, L.I.; Kedes, L.; Chidsey, C.A.; Segel, S. Effect of alterations of coronary blood flow on the oxygen consumption of nonworking heart. Circ. Res. 13: 501–509; 1963.

    CAS  PubMed  Google Scholar 

  19. Kreuzer, F. Oxygen supply to tissues: The Krogh unit and its assumptions. Experientia. 38:1415–1426; 1982.

    Article  CAS  PubMed  Google Scholar 

  20. Krogh, A. The rate of diffusion of gases through animal tissues with some remarks on the coefficient of invasion. J. Physiol. (London). 52:391; 1918.

    Google Scholar 

  21. Lentini, M.; Peyrera, V.. An adaptive finite difference solver for nonlinear two-point boundary problems with mild boundary layers. SIAM J. Num. Anal. 14:91–111; 1979.

    Google Scholar 

  22. Leonard, E.F.; Jorgensen, S.B. The analysis of convection and diffusion in capillary beds. Ann. Rev. Biophys. Bioeng. 3:293–339; 1974.

    CAS  Google Scholar 

  23. Mattiazzi, A.R.; Congolani, H.E.; deCastumam, E.S. Relationship between calcium and hydrogen ions in heart muscle. Am. J. Physiol. 237(4):H497-H503; 1979.

    CAS  PubMed  Google Scholar 

  24. McGilvrey, R.W. Biochemistry. Philadelphia: W.B. Saunders Co; 1970.

    Google Scholar 

  25. Morgenstern, C.; Holjes, U.; Arnold, G.; Lochner, W. The influence of coronary pressure and coronary flow on the intracoronary blood volume and geometry of the left-ventricle. Pflugers Archiv. 340:101–111; 1973.

    Article  CAS  PubMed  Google Scholar 

  26. Napper, S.A. A mathematical model of oxygen transport in isolated heart. Ph.D. Dissertation, Louisiana Tech University; 1985.

  27. Neely, J.R.; Liebermeister, H.; Battersby, E.J.; Morgan, H.E. Effect of pressure development on oxygen consumption by isolated rat heart. Am. J. Physiol. 212(4):804–814; 1967.

    CAS  PubMed  Google Scholar 

  28. Neely, J.R.; Whitmer, J.T.; Rovetto, M.J. Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts. Circ. Res. 37:733–741; 1975.

    CAS  PubMed  Google Scholar 

  29. Nelder, J.A.; Mead, R. A simplex method for functional minimization. Computer J. 7:308; 1965.

    Google Scholar 

  30. Olsen, C.O.; Attarian, D.E.; Jones, R.N.; Hill, R.C.; Sink, J.D.; Lee, K.L.; Wechsler, A.S. The coronary pressure-flow determinants of left ventricular compliance in dogs. Circ. Res. 49:856–865; 1981.

    CAS  PubMed  Google Scholar 

  31. Opie, L.H. Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J. Physiol. 180:529–541; 1965.

    CAS  PubMed  Google Scholar 

  32. Pittman, R.N.; Okusa, M.D. Measurements of oxygen transport in single capillaries. In: Bicher, H.I.; Bruley, D.F., eds. Oxygen transport to tissue-IV. New York: Plenum Press; 1982: pp. 539–553.

    Google Scholar 

  33. Rose, C.P.; Goresky, C.A. Interactions between capillary exchange, cellular entry, and metabolic sequestration processes in the heart. In: Renkin, E.; Geiger, S., eds., Handbook of Physiology. Washington, DC: Vol. 4(2), Am. Physiol. Soc.: 1982.

    Google Scholar 

  34. Salisbury, P.F.; Cross, C.E.; Rieben, P.A. Influence of coronary artery pressure upon myocardial elasticity. Circ. Res. 8:794–800; 1960.

    CAS  PubMed  Google Scholar 

  35. Salisbury, P.F.; Cross, C.E.; Rieben, P.A. Intramyocardial pressure and strength of left ventricular contraction. Circ. Res. 10:608–623; 1962.

    CAS  PubMed  Google Scholar 

  36. Scharf, S.M.; Bromberger-Barnea, B. Influence of coronary flow and pressure on cardiac function and coronary vascular volume. Am. J. Physiol. 224(4):918–925; 1973.

    CAS  PubMed  Google Scholar 

  37. Schubert, R.W. A physiological and mathematical study of oxygen distribution in the autoregulating isolated heart. Ph.D. Dissertation, Case Western Reserve University; 1976.

  38. Schubert, R.W. Myocardial microvascular shunting: Relationship of tissue PO2 and venous PO2. Fed. Proc. 37(4):241; 1978.

    Google Scholar 

  39. Schubert, R.W.; Fletcher, J.E.; Reneau, D.D. An analytical model for axial diffusion in the Krogh cylinder. In: Bruley, D.F.; Bicher, H.I.; Reneau, D.D., eds. Oxygen transport to tissue-VI. New York: Plenum Press; 1984: pp. 433–442.

    Google Scholar 

  40. Schubert, R.W.; Whalen, W.J.; Nair, P. Myocardial PO2 distribution: Relationship to coronary autoregulation. Am. J. Physiol. 234(4):H361-H370; 1978.

    CAS  PubMed  Google Scholar 

  41. Schuchhardt, S.; Losse, B. Static and dynamic behavior of local oxygen pressure in the myocardium. 7th European Conf. Microcirculation, Aberdeen 1972, Part I. Bibl. Anat. No. 11:164–168; 1973.

    CAS  PubMed  Google Scholar 

  42. Schwefel, H.P. Numerical optimization of computer models. Great Britain: John Wiley and Sons; 1981.

    Google Scholar 

  43. Templeton, G.H.; Wildenthal, K.; Mitchell, J.H. Influence of coronary blood flow on left ventricular contractility and stiffness. Am. J. Physiol. 223(5):1216–1220; 1972.

    CAS  PubMed  Google Scholar 

  44. Weisfeldt, M.L.; Shock, N.W. Effect of perfusion pressure on coronary flow and oxygen usage of nonworking heart. Am. J. Physiol. 218(1):95–101; 1970.

    CAS  PubMed  Google Scholar 

  45. Whalen, W.J. Intracellular PO2 in heart and skeletal muscle. Physiologist. 14:69–82; 1971.

    CAS  PubMed  Google Scholar 

  46. Wilson, D.F.; Erecinska, M.; Silver, I.A. Metabolic effects of lowering oxygen tension in vivo. In: Bicher, H.I.; Bruley, D.F., eds. Oxygen transport to tissue-IV. New York: Plenum Press; 1982: pp. 293–301.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Napper, S.A., Schubert, R.W. Mathematical evidence for flow-induced changes in myocardial oxygen consumption. Annals of Biomedical Engineering 16, 349–365 (1988). https://doi.org/10.1007/BF02364623

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02364623

Keywords

Navigation