Redox state of near infrared spectroscopy-measured cytochrome aa(3) correlates with delayed cerebral energy failure following perinatal hypoxia-ischaemia in the newborn pig

Exp Brain Res. 2004 May;156(1):20-6. doi: 10.1007/s00221-003-1761-5. Epub 2003 Dec 20.


Early detection of delayed cerebral energy failure may be important in the prevention of reperfusion injury of the brain after severe perinatal hypoxia-ischaemia (HI). This study investigated whether monitoring of the redox state of cytochrome aa(3) (Cytaa(3)) with near infrared spectroscopy (NIRS) after severe perinatal asphyxia may allow us to detect early a compromised energy metabolism of the developing brain. We therefore correlated serial Cytaa(3) measurements (to estimate mitochondrial oxygenation) simultaneously with the (31)phosphorous-magnetic resonance spectroscopy ((31)P-MRS)-measured phosphocreatin/inorganic phosphate (PCr/Pi) ratio (to estimate cerebral energy reserve) in newborn piglets before and after severe hypoxia-ischaemia. The animals were treated upon reperfusion with either allopurinol, deferoxamine, or 2-iminobiotin or with a vehicle to reduce post-HI reperfusion injury of the brain. Four sham-operated piglets served as controls. Before HI, the individual Cytaa(3) values ranged between -0.02 and 0.71 micromol/L (mean value: -0.07) relative to baseline. The pattern over post-HI time of the vehicle-treated animals was remarkably different from the other groups in as far Cytaa(3) became more oxidised from 3 h after start of HI onwards (increase of Cytaa(3) as compared with baseline), whereas the other groups showed a significant reduction over time (decrease of Cytaa(3) as compared with baseline: allopurinol and deferoxamine) or hardly any change (2-iminobiotin and sham-operated piglets). Vehicle-treated piglets showed a significant reduction in PCr/Pi at 24 h after start of HI, but the cerebral energy state was preserved in 2-iminobiotin-, allopurinol- and deferoxamine-treated piglets. With severe reduction in PCr/Pi-ratio, major changes in the redox-state of Cytaa(3) also occurred: Cytaa(3) was mostly either in a reduced state (down to -6.45 micromol/L) or in an oxidised state (up to 6.84 micromol/L) at these low PCr/Pi ratios. The positive predictive value (PPV) of Cytaa(3) to predict severe reduction of the PCr/Pi ratio was 42%; the negative PPV was 87%. A similar relation was found for Cytaa(3) with histologically determined loss of neurons.

MeSH terms

  • Allopurinol / pharmacology
  • Animals
  • Animals, Newborn
  • Biotin / analogs & derivatives*
  • Biotin / pharmacology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology*
  • Cell Survival / drug effects
  • Deferoxamine / pharmacology
  • Disease Models, Animal
  • Disease Progression
  • Electron Transport Complex IV / metabolism*
  • Energy Metabolism* / drug effects
  • Free Radical Scavengers / pharmacology
  • Hypoxia-Ischemia, Brain / drug therapy
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Iron Chelating Agents / pharmacology
  • Magnetic Resonance Spectroscopy
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Oxidation-Reduction / drug effects
  • Phosphates / metabolism
  • Phosphocreatine / metabolism
  • Predictive Value of Tests
  • Spectroscopy, Near-Infrared
  • Swine


  • Free Radical Scavengers
  • Iron Chelating Agents
  • Neuroprotective Agents
  • Phosphates
  • Phosphocreatine
  • Allopurinol
  • Biotin
  • Electron Transport Complex IV
  • 2-iminobiotin
  • Deferoxamine