title: Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin.
abstract: The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.
authors.affiliation: Dept. of Medical Physics and Bioengineering, University College London, London, UK. Electronic address: c.kolyva@ucl.ac.uk.
authors.forename: Christina
authors.initials: C
authors.lastname: Kolyva
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.forename: Ilias
authors.initials: I
authors.lastname: Tachtsidis
authors.forename: David
authors.initials: D
authors.lastname: Highton
authors.forename: Chris E
authors.initials: CE
authors.lastname: Cooper
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
authors.forename: Clare E
authors.initials: CE
authors.lastname: Elwell
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology*; D002263:Carboxyhemoglobin / Q000032:analysis / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology; D016857:Hypocapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010092:Oximetry / Q000295:instrumentation / Q000379:methods; D010101:Oxygen Consumption / Q000502:physiology*; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D002263:Carboxyhemoglobin; D003576:Electron Transport Complex IV
keywords: Cytochrome c oxidase; Hypercapnia; Hyperoxia; Hypocapnia; Hypoxia; Near-infrared spectroscopy