title: Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy.
abstract: BACKGROUND
  Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy ((31)P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[oxCCO]) and (31)P metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet.
  
  
  METHODS
  Twenty-four piglets (aged<24 h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for ~20 min). Whole-brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by (31)P MRS and were plotted against Δ[oxCCO] during HI and recovery (epp=exchangeable phosphate pool=Pi+PCr+2γ-NTP+β-NTP).
  
  
  RESULTS
  During HI Δ[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between (31)P ratios and Δ[oxCCO]; during HI a threshold point was identified where the relationship between Δ[oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Δ[oxCCO] and (31)P ratios 1h post-HI (survived: 1-h NTP/epp 0.22 ± 0.02, Δ[oxCCO] -0.29 ± 0.50 μM; died: 1-h NTP/epp 0.10 ± 0.04, Δ[oxCCO] -2.41 ± 1.48 μM).
  
  
  CONCLUSIONS
  Both lowered Δ[oxCCO] and NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[oxCCO] and (31)P ratios by 1 h after HI.
authors: Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London NW1 2BU, UK. Electronic address: alan.bainbridge@uclh.nhs.uk.
authors: A
authors: A
authors: Bainbridge
authors: Medical Physics and Bioengineering, University College London, WC1E 6BT, UK.
authors: I
authors: I
authors: Tachtsidis
authors: Institute for Women's Health, University College London, WC1E 6AU, UK.
authors: S D
authors: SD
authors: Faulkner
authors: Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London NW1 2BU, UK.
authors: D
authors: D
authors: Price
authors: Medical Physics and Bioengineering, University College London, WC1E 6BT, UK.
authors: T
authors: T
authors: Zhu
authors: Medical Physics and Bioengineering, University College London, WC1E 6BT, UK.
authors: E
authors: E
authors: Baer
authors: Institute for Women's Health, University College London, WC1E 6AU, UK.
authors: K D
authors: KD
authors: Broad
authors: Institute of Neurology, University College London, London WC1N 3BG, UK.
authors: D L
authors: DL
authors: Thomas
authors: Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London NW1 2BU, UK.
authors: E B
authors: EB
authors: Cady
authors: Institute for Women's Health, University College London, WC1E 6AU, UK.
authors: N J
authors: NJ
authors: Robertson
authors: Institute of Neurology, University College London, London WC1N 3BG, UK.
authors: X
authors: X
authors: Golay
mesh_terms: D000818:Animals; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010759:Phosphorus Isotopes; D019265:Spectroscopy, Near-Infrared; D013552:Swine
chemical_list: D010759:Phosphorus Isotopes
keywords: (31)P; Cytochrome-c-oxidase; Hypoxia–ischemia; MRS; NIRS; Phosphorus
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