Abstract
Near-infrared spectroscopy was used to determine the effect of changes in the rate of oxygen delivery to the adult rat brain on the absolute concentrations of oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was determined to be robust to large changes in haemoglobin oxygenation and concentration. By assuming complete haemoglobin deoxygenation and CuA reduction following mechanical ventilation on 100% N2O, the absolute concentration of oxyhaemoglobin (35 microM), deoxyhaemoglobin (27 microM) and the redox state of CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial blood pressure was decreased by exsanguination. When the pressure reached 100 mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin concentration and oxidized CuA levels only fell when cerebral blood volume autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell linearly with decreases in the rate of oxygen delivery to the brain, but the oxidized CuA concentration did not start to fall until this rate was 50% of normal. The results suggest that the brain maintains more than adequate oxygen delivery to mitochondria and that near-infrared spectroscopy may be a good measure of oxygen insufficiency in vivo.
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- Altman D. I., Perlman J. M., Volpe J. J., Powers W. J. Cerebral oxygen metabolism in newborns. Pediatrics. 1993 Jul;92(1):99–104. [PubMed] [Google Scholar]
- BEINERT H., GRIFFITHS D. E., WHARTON D. C., SANDS R. H. Properties of the copper associated with cytochrome oxidase as studied by paramagnetic resonance spectroscopy. J Biol Chem. 1962 Jul;237:2337–2346. [PubMed] [Google Scholar]
- Babcock G. T., Wikström M. Oxygen activation and the conservation of energy in cell respiration. Nature. 1992 Mar 26;356(6367):301–309. doi: 10.1038/356301a0. [DOI] [PubMed] [Google Scholar]
- Booth R. F., Patel T. B., Clark J. B. The development of enzymes of energy metabolism in the brain of a precocial (guinea pig) and non-precocial (rat) species. J Neurochem. 1980 Jan;34(1):17–25. doi: 10.1111/j.1471-4159.1980.tb04616.x. [DOI] [PubMed] [Google Scholar]
- Brown G. C., Crompton M., Wray S. Cytochrome oxidase content of rat brain during development. Biochim Biophys Acta. 1991 Mar 29;1057(2):273–275. doi: 10.1016/s0005-2728(05)80109-4. [DOI] [PubMed] [Google Scholar]
- Cooper C. E., Cope M., Quaresima V., Ferrari M., Nemoto E., Springett R., Matcher S., Amess P., Penrice J., Tyszczuk L. Measurement of cytochrome oxidase redox state by near infrared spectroscopy. Adv Exp Med Biol. 1997;413:63–73. doi: 10.1007/978-1-4899-0056-2_7. [DOI] [PubMed] [Google Scholar]
- Cooper C. E., Elwell C. E., Meek J. H., Matcher S. J., Wyatt J. S., Cope M., Delpy D. T. The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy. Pediatr Res. 1996 Jan;39(1):32–38. doi: 10.1203/00006450-199601000-00005. [DOI] [PubMed] [Google Scholar]
- Cooper C. E., Matcher S. J., Wyatt J. S., Cope M., Brown G. C., Nemoto E. M., Delpy D. T. Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics. Biochem Soc Trans. 1994 Nov;22(4):974–980. doi: 10.1042/bst0220974. [DOI] [PubMed] [Google Scholar]
- Cooper C. E., Springett R. Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy. Philos Trans R Soc Lond B Biol Sci. 1997 Jun 29;352(1354):669–676. doi: 10.1098/rstb.1997.0048. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper C., Sharpe M., Elwell C., Springett R., Penrice J., Tyszczuk L., Amess P., Wyatt J., Quaresima V., Delpy D. The cytochrome oxidase redox state in vivo. Adv Exp Med Biol. 1997;428:449–456. doi: 10.1007/978-1-4615-5399-1_64. [DOI] [PubMed] [Google Scholar]
- Degn H., Wohlrab H. Measurement of steady-state values of respiration rate and oxidation levels of respiratory pigments at low oxygen tensions. A new technique. Biochim Biophys Acta. 1971 Sep 7;245(2):347–355. doi: 10.1016/0005-2728(71)90153-8. [DOI] [PubMed] [Google Scholar]
- Edwards A. D., Wyatt J. S., Richardson C., Delpy D. T., Cope M., Reynolds E. O. Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. Lancet. 1988 Oct 1;2(8614):770–771. doi: 10.1016/s0140-6736(88)92418-x. [DOI] [PubMed] [Google Scholar]
- Erecińska M., Chance B., Wilson D. F. The oxidation-reduction potential of the copper signal in pigeon heart mitochondria. FEBS Lett. 1971 Sep 1;16(4):284–286. doi: 10.1016/0014-5793(71)80371-x. [DOI] [PubMed] [Google Scholar]
- Ferrari M., Hanley D. F., Wilson D. A., Traystman R. J. Redox changes in cat brain cytochrome-c oxidase after blood-fluorocarbon exchange. Am J Physiol. 1990 Jun;258(6 Pt 2):H1706–H1713. doi: 10.1152/ajpheart.1990.258.6.H1706. [DOI] [PubMed] [Google Scholar]
- Ferrari M., Williams M. A., Wilson D. A., Thakor N. V., Traystman R. J., Hanley D. F. Cat brain cytochrome-c oxidase redox changes induced by hypoxia after blood-fluorocarbon exchange transfusion. Am J Physiol. 1995 Aug;269(2 Pt 2):H417–H424. doi: 10.1152/ajpheart.1995.269.2.H417. [DOI] [PubMed] [Google Scholar]
- Firbank M., Okada E., Delpy D. T. Investigation of the effect of discrete absorbers upon the measurement of blood volume with near-infrared spectroscopy. Phys Med Biol. 1997 Mar;42(3):465–477. doi: 10.1088/0031-9155/42/3/002. [DOI] [PubMed] [Google Scholar]
- Gregory L., Ferguson-Miller S. Independent control of respiration in cytochrome c oxidase vesicles by pH and electrical gradients. Biochemistry. 1989 Mar 21;28(6):2655–2662. doi: 10.1021/bi00432a044. [DOI] [PubMed] [Google Scholar]
- Hampson N. B., Camporesi E. M., Stolp B. W., Moon R. E., Shook J. E., Griebel J. A., Piantadosi C. A. Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans. J Appl Physiol (1985) 1990 Sep;69(3):907–913. doi: 10.1152/jappl.1990.69.3.907. [DOI] [PubMed] [Google Scholar]
- Hill B. C. The reaction of the electrostatic cytochrome c-cytochrome oxidase complex with oxygen. J Biol Chem. 1991 Feb 5;266(4):2219–2226. [PubMed] [Google Scholar]
- Inagaki M., Tamura M. Preparation and optical characteristics of hemoglobin-free isolated perfused rat head in situ. J Biochem. 1993 Jun;113(6):650–657. doi: 10.1093/oxfordjournals.jbchem.a124098. [DOI] [PubMed] [Google Scholar]
- Iwata S., Ostermeier C., Ludwig B., Michel H. Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature. 1995 Aug 24;376(6542):660–669. doi: 10.1038/376660a0. [DOI] [PubMed] [Google Scholar]
- Jöbsis F. F., Keizer J. H., LaManna J. C., Rosenthal M. Reflectance spectrophotometry of cytochrome aa3 in vivo. J Appl Physiol Respir Environ Exerc Physiol. 1977 Nov;43(5):858–872. doi: 10.1152/jappl.1977.43.5.858. [DOI] [PubMed] [Google Scholar]
- Kariman K., Burkhart D. S. Non-invasive in vivo spectrophotometric monitoring of brain cytochrome aa3 revisited. Brain Res. 1985 Dec 23;360(1-2):203–213. doi: 10.1016/0006-8993(85)91236-3. [DOI] [PubMed] [Google Scholar]
- Klein J. O., Teele D. W., Kulkarni R. A. In vitro Activity of Selected Cephalosporins and Penicillins against Bacteria of Importance in Infections of Infants and Children. Proc R Soc Med. 1977;70(Suppl 9):198–199. doi: 10.1177/00359157770700S948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LaManna J. C., Sick T. J., Pikarsky S. M., Rosenthal M. Detection of an oxidizable fraction of cytochrome oxidase in intact rat brain. Am J Physiol. 1987 Sep;253(3 Pt 1):C477–C483. doi: 10.1152/ajpcell.1987.253.3.C477. [DOI] [PubMed] [Google Scholar]
- Macnab A. J., Gagnon R. E. Potential sources of discrepancies between living tissue near infrared spectroscopy algorithms. Anal Biochem. 1996 May 1;236(2):375–377. doi: 10.1006/abio.1996.0189. [DOI] [PubMed] [Google Scholar]
- Matcher S. J., Cooper C. E. Absolute quantification of deoxyhaemoglobin concentration in tissue near infrared spectroscopy. Phys Med Biol. 1994 Aug;39(8):1295–1312. doi: 10.1088/0031-9155/39/8/008. [DOI] [PubMed] [Google Scholar]
- Matcher S. J., Elwell C. E., Cooper C. E., Cope M., Delpy D. T. Performance comparison of several published tissue near-infrared spectroscopy algorithms. Anal Biochem. 1995 May 1;227(1):54–68. doi: 10.1006/abio.1995.1252. [DOI] [PubMed] [Google Scholar]
- Miyake H., Nioka S., Zaman A., Smith D. S., Chance B. The detection of cytochrome oxidase heme iron and copper absorption in the blood-perfused and blood-free brain in normoxia and hypoxia. Anal Biochem. 1991 Jan;192(1):149–155. doi: 10.1016/0003-2697(91)90200-d. [DOI] [PubMed] [Google Scholar]
- Morgan J. E., Wikström M. Steady-state redox behavior of cytochrome c, cytochrome a, and CuA of cytochrome c oxidase in intact rat liver mitochondria. Biochemistry. 1991 Jan 29;30(4):948–958. doi: 10.1021/bi00218a010. [DOI] [PubMed] [Google Scholar]
- Nicholls P. Control of proteoliposomal cytochrome c oxidase: the partial reactions. Biochem Cell Biol. 1990 Sep;68(9):1135–1141. doi: 10.1139/o90-169. [DOI] [PubMed] [Google Scholar]
- Oshino N., Sugano T., Oshino R., Chance B. Mitochondrial function under hypoxic conditions: the steady states of cytochrome alpha+alpha3 and their relation to mitochondrial energy states. Biochim Biophys Acta. 1974 Dec 19;368(3):298–310. doi: 10.1016/0005-2728(74)90176-5. [DOI] [PubMed] [Google Scholar]
- Piantadosi C. A., Sylvia A. L. Cerebral cytochrome a,a3 inhibition by cyanide in bloodless rats. Toxicology. 1984 Oct;33(1):67–79. doi: 10.1016/0300-483x(84)90017-9. [DOI] [PubMed] [Google Scholar]
- Portnoy H. D., Chopp M., Branch C. Hydraulic model of myogenic autoregulation and the cerebrovascular bed: the effects of altering systemic arterial pressure. Neurosurgery. 1983 Nov;13(5):482–498. doi: 10.1227/00006123-198311000-00002. [DOI] [PubMed] [Google Scholar]
- Rich P. R., West I. C., Mitchell P. The location of CuA in mammalian cytochrome c oxidase. FEBS Lett. 1988 Jun 6;233(1):25–30. doi: 10.1016/0014-5793(88)81349-8. [DOI] [PubMed] [Google Scholar]
- Rumsey W. L., Schlosser C., Nuutinen E. M., Robiolio M., Wilson D. F. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem. 1990 Sep 15;265(26):15392–15402. [PubMed] [Google Scholar]
- Schlichtig R., Klions H. A., Kramer D. J., Nemoto E. M. Hepatic dysoxia commences during O2 supply dependence. J Appl Physiol (1985) 1992 Apr;72(4):1499–1505. doi: 10.1152/jappl.1992.72.4.1499. [DOI] [PubMed] [Google Scholar]
- Skov L., Greisen G. Apparent cerebral cytochrome aa3 reduction during cardiopulmonary bypass in hypoxaemic children with congenital heart disease. A critical analysis of in vivo near-infrared spectrophotometric data. Physiol Meas. 1994 Nov;15(4):447–457. doi: 10.1088/0967-3334/15/4/006. [DOI] [PubMed] [Google Scholar]
- Stingele R., Wagner B., Kameneva M. V., Williams M. A., Wilson D. A., Thakor N. V., Traystman R. J., Hanley D. F. Reduction of cytochrome-c oxidase copper precedes failing cerebral O2 utilization in fluorocarbon-perfused cats. Am J Physiol. 1996 Aug;271(2 Pt 2):H579–H587. doi: 10.1152/ajpheart.1996.271.2.H579. [DOI] [PubMed] [Google Scholar]
- 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 Jun 28;347(3):340–358. doi: 10.1016/0005-2728(74)90074-7. [DOI] [PubMed] [Google Scholar]
- Sylvia A. L., Piantadosi C. A. O2 dependence of in vivo brain cytochrome redox responses and energy metabolism in bloodless rats. J Cereb Blood Flow Metab. 1988 Apr;8(2):163–172. doi: 10.1038/jcbfm.1988.45. [DOI] [PubMed] [Google Scholar]
- Tamura M. Non-invasive monitoring of the redox state of cytochrome oxidase in living tissue using near-infrared laser lights. Jpn Circ J. 1993 Aug;57(8):817–824. doi: 10.1253/jcj.57.817. [DOI] [PubMed] [Google Scholar]
- Tamura M. Protective effects of a PGI2 analogue OP-2507 on hemorrhagic shock in rats--with an evaluation of the metabolic recovery using near-infrared optical monitoring. Jpn Circ J. 1992 Apr;56(4):366–375. doi: 10.1253/jcj.56.366. [DOI] [PubMed] [Google Scholar]
- Thörnström P. E., Brzezinski P., Fredriksson P. O., Malmström B. G. Cytochrome c oxidase as an electron-transport-driven proton pump: pH dependence of the reduction levels of the redox centers during turnover. Biochemistry. 1988 Jul 26;27(15):5441–5447. doi: 10.1021/bi00415a009. [DOI] [PubMed] [Google Scholar]
- 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 Mar;37(3):253–259. doi: 10.1203/00006450-199503000-00001. [DOI] [PubMed] [Google Scholar]
- Tsukihara T., Aoyama H., Yamashita E., Tomizaki T., Yamaguchi H., Shinzawa-Itoh K., Nakashima R., Yaono R., Yoshikawa S. Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A. Science. 1995 Aug 25;269(5227):1069–1074. doi: 10.1126/science.7652554. [DOI] [PubMed] [Google Scholar]
- Tuor U. I., Grewal D. Autoregulation of cerebral blood flow: influence of local brain development and postnatal age. Am J Physiol. 1994 Dec;267(6 Pt 2):H2220–H2228. doi: 10.1152/ajpheart.1994.267.6.H2220. [DOI] [PubMed] [Google Scholar]
- Vern B. A., Schuette W. H., Leheta B., Juel V. C., Radulovacki M. Low-frequency oscillations of cortical oxidative metabolism in waking and sleep. J Cereb Blood Flow Metab. 1988 Apr;8(2):215–226. doi: 10.1038/jcbfm.1988.52. [DOI] [PubMed] [Google Scholar]
- Wilson D. F., Erecińska M., Drown C., Silver I. A. The oxygen dependence of cellular energy metabolism. Arch Biochem Biophys. 1979 Jul;195(2):485–493. doi: 10.1016/0003-9861(79)90375-8. [DOI] [PubMed] [Google Scholar]
- Wilson D. F., Erecińska M., Owen C. S. Some properties of the redox components of cytochrome c oxidase and their interactions. Arch Biochem Biophys. 1976 Jul;175(1):160–172. doi: 10.1016/0003-9861(76)90495-1. [DOI] [PubMed] [Google Scholar]
- Wilson D. F., Rumsey W. L., Green T. J., Vanderkooi J. M. The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration. J Biol Chem. 1988 Feb 25;263(6):2712–2718. [PubMed] [Google Scholar]
- Wyatt J. S., Cope M., Delpy D. T., Richardson C. E., Edwards A. D., Wray S., Reynolds E. O. Quantitation of cerebral blood volume in human infants by near-infrared spectroscopy. J Appl Physiol (1985) 1990 Mar;68(3):1086–1091. doi: 10.1152/jappl.1990.68.3.1086. [DOI] [PubMed] [Google Scholar]
