Regulation of Cerebral Oxygen Delivery

  • Fahmeed Hyder
  • Robert G. Shulman
  • Douglas L. Rothman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 471)

Abstract

Under normal conditions, it is generally accepted that for the adult mammalian cortex, almost all the energy required for cerebral ATP generation is supplied by oxidation of glucose through the tri-carboxylic acid cycle (Siesjö, 1978), and cerebral metabolic rates of oxygen and glucose use (i.e., CMRO2 and CMRglc, respectively) are regionally modified to fulfil metabolic needs through regulation of cerebral blood flow (CBF) and volume (CBV) (Roy and Sherrington, 1890). However, some positron emission tomography (PET) results have reported that during brain activation of awake humans CBF increases by a greater fraction than CMRO2 (Fox and Raichle, 1986; Fox et al., 1988). In the last few decades, ever since in vivo cortical measurements could be made of CBF and/or CMRO2, the mechanisms for the proportionality of changes between CBF and CMRO2 due to physiological perturbations have remained intangible, and the measured stoichiometries have varied reflecting a variety of experimental methods and/or conditions. However, regionally tight relationship between CMRO2 and CBF has been observed at rest with a ratio of about ~1:1 (Kety et al., 1947–8; Raichle et al., 1976).

Keywords

Permeability Dioxide Ischemia Albumin Schizophrenia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abounader R, Vodel J, and Kuschinsky W (1995) Patterns of capillary plasma perfusion in brains of conscious rats during normocapnia and hypercapnia. Circ Res 76:120–126.CrossRefPubMedGoogle Scholar
  2. Atkinson JLD, Anderson RE, and Sundt Jr. TM (1990) The effect of carbon dioxide on the diameter of brain capillaries. Brain Res 517:333–340.CrossRefPubMedGoogle Scholar
  3. Bassingthwaighte JB (1974) A concurrent flow model for extraction during transcapillary passage. Circ Res 35:483–503.CrossRefPubMedGoogle Scholar
  4. Buxton RB and Frank LR (1997) A model of the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J Cereb Blood Flow Metab 17:64–72.CrossRefPubMedGoogle Scholar
  5. Clark Jr. A, Federspiel WJ, Clark PAA, and Cokelet GR (1985) Oxygen delivery from red cells Biophys. J 47:171–181.CrossRefPubMedGoogle Scholar
  6. Cox SB, Woolsey TA, and Romaines CM (1993) Localized dynamic changes in cortical blood flow with whisker stimulation corresponds to matched vascular and neuronal architecture of rat barrels. J Cereb Blood Flow Metab 13:899–913.CrossRefPubMedGoogle Scholar
  7. Crone C (1963) The permeability of capillaries in various organs as determined by the “indicator diffusion” method. Acta Physiol Scand 58:292–305.CrossRefPubMedGoogle Scholar
  8. Davis TL, Kwong KK, Weisskoff RM, and Rosen BR (1998) Calibrated functional MRI: Mapping the dynamics of oxidative metabolism. Proc Natl Acad Sci USA 95:1834–1839.CrossRefPubMedGoogle Scholar
  9. Ducharme R, Kapadia P, and Dowden J (1991) A mathematical model of the flow of blood cells in fine capillaries. J Biomech 24:299–306.CrossRefPubMedGoogle Scholar
  10. Federspiel WJ and Sarelius IH (1984) An examination of the contribution of red cell spacing to the uniformity of oxygen flux at the capillary wall. Mircovasc Res 27:273–285.CrossRefGoogle Scholar
  11. Fox PT and Raichle ME (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 83:1140–1144.CrossRefPubMedGoogle Scholar
  12. Fox PT, Raichle ME, Mintun MA, and Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–464.CrossRefPubMedGoogle Scholar
  13. Ginsberg MD, Dietrich WD, and Busto R (1987) Coupled forebrain increases of local cerebral glucose utilization and blood flow during physiologic stimulation of a somatosensory pathway in the rat: Demonstration by double-label autoradiography. Neurology 37:11–19.CrossRefPubMedGoogle Scholar
  14. Gjedde A (1997) The relation between brain function and cerebral blood flow and metabolism. In: Cerebrovascular Disease (Batjer HH, Ed) Lippincott-Raven, Philadelphia, pp. 23–40.Google Scholar
  15. Gjedde A (1991) Is oxygen diffusion limiting for blood-brain transfer of oxygen? In: Brain Work and Mental Activity, Alfred Benzon Symposium 31 (Lassen NA, Ingvar DH, Raichle ME, Friberg L, Eds) Munksgaard, Copenhagen, pp. 177–184.Google Scholar
  16. Hägerdal M, Hamp JR, Nillson L, and Siesjö BK (1975) The effect of induced hypothermia upon oxygen consumption in rat brain. J Neurochem 24:311–316.CrossRefPubMedGoogle Scholar
  17. Homer LD, Weathersby PK, and Kiesow LA (1981) Oxygen gradients between red blood cells in the microcirculation. Mircovasc Res 22:232–308.CrossRefGoogle Scholar
  18. Hyder F, Chase JR, Behar KL, Mason GF, Siddeek M, Rothman DL, and Shulman RG (1996) Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H-[13C] NMR. Proc Natl Acad Sci USA 93:7612–7617.CrossRefPubMedGoogle Scholar
  19. Hyder F, Rothman DL, Mason GF, Rangarajan A, Behar KL, and Shulman RG (1997) Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1H[13C] NMR Study. J Cereb Blood Flow Metab 17:1040–1047.CrossRefPubMedGoogle Scholar
  20. Hyder F, Shulman RG, and Rothman DL (1998a) A model for the regulation of cerebral oxygen delivery. J Appl Physiol 85:554–564.PubMedGoogle Scholar
  21. Hyder F, Kennan RP, Sibson NR, Mason GF, Behar KL, Rothman DL, and Shulman RG (1998b) Cerebral oxygen delivery in vivo: NMR measurements of CBF and CMRO2 at different levels of brain activity. Soc Magn Reson Med Abstr p. 1160.Google Scholar
  22. Kassissia IG, Goresky CA, Rose CP, Schwab AJ, Simard A, and Huet PM (1995) Tracer oxygen distribution is barrier-limited in cerebral microcirculation. Circ Res 77:1201–1211.CrossRefPubMedGoogle Scholar
  23. Kety SS, Woodford RB, Harmel MH, Freyhan FA, Appel KE, and Schmidt CF (1947-8) Cerebral blood flow and metabolism in schizophrenia. The effect of barbiturate semi-narcosis, insulin coma and electroshock. Amer J Psychiat 104:765–770.Google Scholar
  24. Kreuzer F (1982) Oxygen supply to tissues: the Krogh model and its assumptions. Experimentia 38:1415–1426.CrossRefGoogle Scholar
  25. Krogh A (1919) The number and the distribution of capillaries in muscles with the calculation of the oxygen pressure head necessary for supplying the tissue. J Physiol (Lond) 52:409–441.Google Scholar
  26. Lenigert-Follert E (1975) Direct determination of local oxygen consumption of the brain cortex in vivo. Plügers Arch 372:175–179.CrossRefGoogle Scholar
  27. Meier P and Zierler KL (1954) On the Theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 6:731–744.PubMedGoogle Scholar
  28. Meldrum BS and Nilsson B (1976) Cerebral blood flow and metabolic rate early and late in prolonged seizures induced in rats by bicuculline. Brain 99:523–542.CrossRefPubMedGoogle Scholar
  29. Metzger H and Heuber S (1977) Local oxygen tension and spike activity of the cerebral grey matter of the rat and its response to short intervals of O2 deficiency or CO2 excess. Plügers Arch 370:201–209.CrossRefGoogle Scholar
  30. Moss GS, Dewoskin R, Rosen AL, Levine H, and Palani CK (1976) Transport of oxygen and carbon dioxide by hemoglobin-saline solution in the red-cell-free primate. Surg Gynecol Obstet 142:357–362.PubMedGoogle Scholar
  31. Narain SM, Esfahani P, Blood AJ, Sikkens L, and Toga AW (1995) Functional increases in cerebral blood volume over somatosensory cortex. J Cereb Blood Flow Metab 15:754–765.CrossRefGoogle Scholar
  32. Nilsson B and Siesjö BK (1975) The effect of phenobarbitone anaesthesia on blood flow and oxygen consumption in the rat brain. Acta Annaesthesiol Scand Suppl 57:18–24, 1975.CrossRefGoogle Scholar
  33. Nilsson B and Siesjö BK (1976) A method of determining blood flow and oxygen consumption in rat brain. Acta Physiol Scand 17:273–282.Google Scholar
  34. Pierce Jr EC, Lambersten CL, Deutsch S, Chase PA, Linde HW, Dripps RD, and Price HL (1962) Cerebral circulation and metabolism during thiopental anaesthesia and hyperventilation in man. J Clin Invest 41:1664–1671.CrossRefPubMedGoogle Scholar
  35. Pries AR, Secomb TW, and Gaehtgens P (1996) Relationship between structural and hemodynamic heterogeneity in micro vascular networks. Am J Physiol 270:H545–H553.PubMedGoogle Scholar
  36. Raichle ME, Grubb RL, Gado MH, Eichling JO, and Ter-Pogossian MM (1976) Correlation between regional cerebral blood flow and oxidative metabolism. Arch Neurol 33:523–526.CrossRefPubMedGoogle Scholar
  37. Raichle ME (1987) Circulatory and metabolic correlates of brain function in normal humans. In: Handbook of Physiology. The Nervous System. Higher Functions of the Brain. Bethesda, MD: AM Physiol Soc, sect 1, vol V, pt. 2, chapt 16, pp. 633–674.Google Scholar
  38. Renkin EM (1959) Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscle. Am J Physiol 197:1205–1210.PubMedGoogle Scholar
  39. Roland PE, Eriksson L, Atone-Elander S, and Widen L (1987) Does mental activity change the oxidative metabolism of the brain? J Neurosci 7:2373–2389.PubMedGoogle Scholar
  40. Romaines CM, Woolsey TA, Blocher NC, Wang D-B, and Robinson OF (1993) Blood flow in single surface arterioles and venules on the mouse somatosensory cortex measured with videomicroscopy, flourescent dextrans, non-occluding flourescent beads, and computer-assisted image analysis. J Cereb Blood Flow Metab 13:271–359.Google Scholar
  41. Roy CS and Sherrington CS (1890) On the regulation of the blood supply of the rat brain. J Physiol (Lond) 11:85–108.Google Scholar
  42. Scitz RJ and Roland PE (1992) Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. Acta Neurol Scand 86:60–67.CrossRefGoogle Scholar
  43. Siesjö BK (1978) Brain Energy Metabolism. Wiley, New York.Google Scholar
  44. Smith AL and Wollman H (1972) Cerebral blood flow and metabolism. Anesthesiology 36:378–400.CrossRefPubMedGoogle Scholar
  45. Stewart GN (1894) Researches on the circulation time in organs and on the influences which affect it: parts I-III. J Physiol (Lond) 15:1–27.Google Scholar
  46. Tajima A, Nakata H, Lin S-Z, Acuff V, and Fenstermacher J (1992) Differences and similarities in albumin and red blood cell flows through microvessels. Am J Physiol 262:H1515–H1524.PubMedGoogle Scholar
  47. Ueki M, Linn F, and Hossmann K-A (1988) Functional activation of cerebral blood flow and metabolism after global ischemia of rat brain. J Cereb Blood Flow Metab 8:486–494.CrossRefPubMedGoogle Scholar
  48. Vetterlein F, Demmerle B, Bardosi A, Göbel U, and Schmidt G (1990) Determination of capillary perfusion pattern in rat brain by timed plasma labelling. Am J Physiol 258:H80–H84.PubMedGoogle Scholar
  49. Villringer A, Planck J, Hock C, Schleinkofer L, and Dirnagl U (1993) A new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett 154:101–104.CrossRefPubMedGoogle Scholar
  50. Villringer A, Them A, Lindauer U, Einhäul K, and Dirnagl U (1994) Capillary perfusion in rat brain cortex. Circ Res 75:55–62.CrossRefPubMedGoogle Scholar
  51. Walley KR (1996) Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory. J Appl Physiol 81:885–894.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Fahmeed Hyder
    • 1
  • Robert G. Shulman
    • 2
  • Douglas L. Rothman
    • 1
  1. 1.Department of Diagnostic RadiologyYale UniversityNew HavenUSA
  2. 2.Department of Molecular Biophysics and BiochemistryYale UniversityNew HavenUSA

Personalised recommendations