title: Hyperoxia results in increased aerobic metabolism following acute brain injury.
abstract: Acute brain injury is associated with depressed aerobic metabolism. Below a critical mitochondrial pO2cytochrome c oxidase, the terminal electron acceptor in the mitochondrial respiratory chain, fails to sustain oxidative phosphorylation. After acute brain injury, this ischaemic threshold might be shifted into apparently normal levels of tissue oxygenation. We investigated the oxygen dependency of aerobic metabolism in 16 acutely brain-injured patients using a 120-min normobaric hyperoxia challenge in the acute phase (24-72 h) post-injury and multimodal neuromonitoring, including transcranial Doppler ultrasound-measured cerebral blood flow velocity, cerebral microdialysis-derived lactate-pyruvate ratio (LPR), brain tissue pO2(pbrO2), and tissue oxygenation index and cytochrome c oxidase oxidation state (oxCCO) measured using broadband spectroscopy. Increased inspired oxygen resulted in increased pbrO2[ΔpbrO230.9 mmHg p < 0.001], reduced LPR [ΔLPR -3.07 p = 0.015], and increased cytochrome c oxidase (CCO) oxidation (Δ[oxCCO] + 0.32 µM p < 0.001) which persisted on return-to-baseline (Δ[oxCCO] + 0.22 µM, p < 0.01), accompanied by a 7.5% increase in estimated cerebral metabolic rate for oxygen ( p = 0.038). Our results are consistent with an improvement in cellular redox state, suggesting oxygen-limited metabolism above recognised ischaemic pbrO2thresholds. Diffusion limitation or mitochondrial inhibition might explain these findings. Further investigation is warranted to establish optimal oxygenation to sustain aerobic metabolism after acute brain injury.
authors.affiliation: 1 Neurocritical Care, University College London Hospitals, National Hospital for Neurology & Neurosurgery, London, UK.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: 1 Neurocritical Care, University College London Hospitals, National Hospital for Neurology & Neurosurgery, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Highton
authors.affiliation: 2 Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Kolyva
authors.affiliation: 2 Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: Ilias
authors.initials: I
authors.lastname: Tachtsidis
authors.affiliation: 2 Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Elwell
authors.affiliation: 1 Neurocritical Care, University College London Hospitals, National Hospital for Neurology & Neurosurgery, London, UK.|2 Department of Medical Physics and Biomedical Engineering, University College London, London, UK.|3 University College London Hospitals National Institute for Health Research Biomedical Research Centre, London, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
mesh_terms: D001783:Blood Flow Velocity / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D018496:Hyperoxia / Q000000981:diagnostic imaging / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D017551:Microdialysis; D008928:Mitochondria / Q000378:metabolism; D064926:Neurophysiological Monitoring / Q000379:methods*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology*; D019289:Pyruvic Acid / Q000378:metabolism; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D019344:Lactic Acid; D019289:Pyruvic Acid; D045304:Cytochromes c
keywords: Brain ischaemia; energy metabolism; mitochondria; near infrared spectroscopy; neurocritical care