title: Reduction of cytochrome-c oxidase copper precedes failing cerebral O2 utilization in fluorocarbon-perfused cats.
abstract: We determined the relationship of the low-potential copper (CuA) redox state of cytochrome-c oxidase to the brain tissue PO2 (PtiO2) and global cerebral O2 consumption (CMRO2) in vivo. The redox state of cytochrome-c oxidase copper was monitored in perfluorocarbon-exchanged cats under normoxic and graded hypoxic conditions with use of near-infrared spectroscopy. Continuous spectra ranging from 730 to 960 nm were acquired, and the change in copper redox state was assessed by the absorption changes at 830 nm. PtiO2 was measured with O2-sensitive electrodes implanted into the cortex, and CMRO2 was determined by sampling arterial and superior sagittal sinus perfusate and by measuring blood flow with radiolabeled microspheres. As PtiO2 decreased with hypoxia, the CuA of cytochrome-c oxidase became progressively reduced, whereas the CMRO2 was unchanged during the initial stages of hypoxia. Only with severe hypoxia, did CMRO2 and the amplitude of somatosensory evoked potentials decrease. We conclude that the CuA site of cytochrome-c oxidase is involved in a regulatory adjustment that helps maintain CMRO2 constant.
authors.affiliation: Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: R
authors.initials: R
authors.lastname: Stingele
authors.forename: B
authors.initials: B
authors.lastname: Wagner
authors.forename: M V
authors.initials: MV
authors.lastname: Kameneva
authors.forename: M A
authors.initials: MA
authors.lastname: Williams
authors.forename: D A
authors.initials: DA
authors.lastname: Wilson
authors.forename: N V
authors.initials: NV
authors.lastname: Thakor
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
authors.forename: D F
authors.initials: DF
authors.lastname: Hanley
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D002415:Cats; D003300:Copper / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005073:Evoked Potentials, Somatosensory; D005260:Female; D005466:Fluorocarbons; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010477:Perfusion; D012016:Reference Values; D013055:Spectrophotometry, Infrared; D014783:Viscosity
chemical_list: D005466:Fluorocarbons; D003300:Copper; D003576:Electron Transport Complex IV