The Oxygen Dependency of Cerebral Oxidative Metabolism in the Newborn Piglet Studied with 31P NMRS and NIRS

  • Roger J Springett
  • Marzena Wylezinska
  • Ernest B. Cady
  • Veronica Hollis
  • Mark Cope
  • David T. Delpy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 530)


Mean cerebral saturation and changes in the oxidation state of the CuA centre of cytochrome oxidase were measured by near infra-red spectroscopy simultaneously with phosphorous metabolites and intracellular pH measured using 31P NMR spectroscopy during transient anoxia (inspired oxygen fraction = 0.0 for 105 seconds) in the newborn piglet brain. By collecting high quality 31 P spectra every 10 seconds, it was possible to resolve the delay between the onset of anoxia and the fall in PCr and to show that the CuA centre of cytochrome oxidase reduced simultaneously with the fall in PCr. From these observations it is concluded that, at normoxia, oxygen tension at the mitochondrial level is substantially above a critical value at which oxidative metabolism becomes oxygen dependent.

Key words

NIRS 31P NMRS cytochrome oxidase hypoxia 


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  1. 1.
    Siesjo BK. Brain Energy metabolism, John Wiley & Sons, Chichester, 1978.Google Scholar
  2. 2.
    Sugano T, Oshino N, Chance B. Mitochondrial functions under hypoxic conditions. The steady states of cytochrome c reduction and of energy metabolism. Biochim. Biophys. Acta 1974;347:340–358.PubMedCrossRefGoogle Scholar
  3. 3.
    Wilson DF, Erecsinska M, Drown C, Silver IA. Effects of oxygen tension on cellular energetics. Amer. J. Physiol. 1977;233: C135–140.Google Scholar
  4. 4.
    Wilson DF, Erecsinska M, Drown C, Silver IA. The oxygen dependence of cellular energy metabolism. Arch. Biochem. Biophys. 1979;195:485–493.PubMedCrossRefGoogle Scholar
  5. 5.
    Hampson NB, Camporesi EM, Stolp BW, Moon RE, Shook JE, Griebel JA, Piantadosi CA. Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans. J. Appl. Physiol. 1990;69:907–913.PubMedGoogle Scholar
  6. 6.
    Hoshi Y, Hazeki O, Kakihana Y, Tamura M Redox behavior of cytochrome oxidase in the rat brain measured by near-infrared spectroscopy. J Appl Physiol 1997;83:18421848.Google Scholar
  7. 7.
    Cooper CE, Matcher SJ, Wyatt JS, Cope M, Brown GC, Nemoto EM, Delpy DT. Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics. Biochem Soc Trans 1994;22:974–980.PubMedGoogle Scholar
  8. 8.
    Matcher SJ, Elwell CE, Cooper CE, Cope M Delpy DT. Performance comparison of several published tissue near-infrared spectroscopy algorithms. Anal. Biochem. 1994;227: 54–68.CrossRefGoogle Scholar
  9. 9.
    Matcher SJ, Cope M, Delpy DT. Use of the water-absorption spectrum to quantify tissue chromophore concentration changes in near-infrared spectroscopy. Phys. Med. Biol. 1994;39:177–196.PubMedCrossRefGoogle Scholar
  10. 10.
    Tsuji M, Naruse H, Volpe J, Holtzman D. Reduction of cytochrome aa3 measured by near-infrared spectroscopy predicts cerebral energy loss in hypoxic piglets. Pediatr. Res. 1995;37 253–259.PubMedCrossRefGoogle Scholar
  11. 11.
    Matsumoto H, Oda T, Hossain MA, Yoshimura N. Does the redox state of cytochrome aa3 reflect brain energy level during hypoxia? Simultaneous measurements by near infrared spectrophotometry and 31P nuclear magnetic resonance spectroscopy. Anesth Analg 1996;83:513–518.PubMedGoogle Scholar
  12. 12.
    Gyulai L, Chance B, Ligeti L, McDonald G, Cone J. Correlated in vivo 31P-NMR and NADH fluorometric studies on gerbil brain in graded hypoxia and hyperoxia. Am. J. Physiol. 1988;254: C699–C708.PubMedGoogle Scholar
  13. 13.
    Morris P., Freeman R. Selective excitation in Fourier transform nuclear magnetic resonance. J. Magn. Reson. Imaging 1978;29:433–462.Google Scholar
  14. 14.
    Moon RB Richards JH. Determination of intracellular pH by 31P magnetic resonance. J. Biol. Chem. 1973;48: 7276–7278.Google Scholar
  15. 15.
    Cooper CE, Cope M, Springett R, Amess PN, Penrice J, Tyszczuk L, Punwani S, Ordidge R Wyatt J, Delpy DT Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondria] dysfunction non-invasively in the brain J. Cereb. Blood Flow Metab. 1999;19,27–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Medina JM, Tabernero A, Tovar JA, Martin-Barrientos. Metabolic fuel utilization and pyruvate oxidation during the postnatal period. J Inherit Metab Dis 1996;19:432–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Iwata S, Ostermeier C, Ludwig B and Michel H. Structure at 2.8A resolution of cytochrome c oxidase from Paracoccus Denitrificans. Nature 1995;376: 660–669.PubMedCrossRefGoogle Scholar
  18. 18.
    Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R and Yoshikawa S. Structure of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8A. Science 1995; 269: 1069–1074.PubMedCrossRefGoogle Scholar
  19. 19.
    Rich PR, West IC and Mitchell P. The location of CuA in mammalian cytochrome c oxidase. FEBS Lett. 1988; 233: 25–30.PubMedCrossRefGoogle Scholar
  20. 20.
    Morgan JE, Wikström M. Steady-state redox behaviour of cytochrome c, cytochrome a, and CuA of cytochrome oxidase in intact rat liver mitochondria. Biochemistry 1991; 30: 984–958.CrossRefGoogle Scholar
  21. 21.
    Kokholm G. Simultaneous measurements of blood pH, pCO2, p02 and concentrations of hemoglobin and its derivates--a multicenter study. Scand J Clin Lab Invest Suppl 1990; 203:75–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Gyulai L, Schnall M, McLaughlin AC, Leigh JS, Chance B (1987) Simultaneous 31P and 1H-nuclear magnetic resonance studies of hypoxia and ischaemia in the cat brain J. Cereb. Blood Flow Metab. 7:543–551.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Roger J Springett
    • 1
  • Marzena Wylezinska
    • 2
  • Ernest B. Cady
    • 2
  • Veronica Hollis
    • 3
  • Mark Cope
    • 3
  • David T. Delpy
    • 3
  1. 1.Department of RadiologyDartmouth CollegeHanoverUSA
  2. 2.University College Hospitals NHS TrustLondonUK
  3. 3.Department of Medical Physics & BioengineeringUniversity College LondonLondonUK

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