title: Near-infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia.
abstract: The near-IR cytochrome c oxidase (CCO) signal has potential as a clinical marker of changes in mitochondrial oxygen utilization. We examine the CCO signal response to reduced oxygen delivery in the healthy human brain. We induced a reduction in arterial oxygen saturation from baseline levels to 80% in eight healthy adult humans, while minimizing changes in end tidal carbon dioxide tension. We measured changes in the cerebral concentrations of oxidized CCO (Delta[oxCCO]), oxyhemoglobin (Delta[HbO(2)]), and deoxyhemoglobin (Delta[HHb]) using broadband near-IR spectroscopy (NIRS), and estimated changes in cerebral oxygen delivery (ecDO(2)) using pulse oximetry and transcranial Doppler ultrasonography. Results are presented as median (interquartile range). At the nadir of hypoxemia ecDO(2) decreased by 9.2 (5.4 to 12.1)% (p<0.0001), Delta[oxCCO] decreased by 0.24 (0.06 to 0.28) micromoles/l (p<0.01), total hemoglobin concentration increased by 2.83 (2.27 to 4.46) micromoles/l (p<0.0001), and change in hemoglobin difference concentration (Delta[Hbdiff]=Delta[HbO(2)]-Delta[HHb]) decreased by 12.72 (11.32 to 16.34) micromoles/l (p<0.0001). Change in ecDO(2) correlated with Delta[oxCCO] (r=0.78, p<0.001), but not with either change in total hemoglobin concentration or Delta[Hbdiff]. This is the first description of cerebral Delta[oxCCO] during hypoxemia in healthy adults. Studies are ongoing to investigate the clinical relevance of this signal in patients with traumatic brain injury.
authors.affiliation: The National Hospital for Neurology and Neurosurgery, Department of Neuroanaesthesia and Neurocritical Care, Queen Square, London WC1N 3BG, United Kingdom. m.tisdall@ion.ucl.ac.uk
authors.forename: Martin M
authors.initials: MM
authors.lastname: Tisdall
authors.forename: Ilias
authors.initials: I
authors.lastname: Tachtsidis
authors.forename: Terence S
authors.initials: TS
authors.lastname: Leung
authors.forename: Clare E
authors.initials: CE
authors.lastname: Elwell
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D008297:Male; D010084:Oxidation-Reduction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D003576:Electron Transport Complex IV