Abstract
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 aa3 (Cytaa3) 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 Cytaa3 measurements (to estimate mitochondrial oxygenation) simultaneously with the 31phosphorous-magnetic resonance spectroscopy (31P-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 Cytaa3 values ranged between −0.02 and 0.71 μmol/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 Cytaa3 became more oxidised from 3 h after start of HI onwards (increase of Cytaa3 as compared with baseline), whereas the other groups showed a significant reduction over time (decrease of Cytaa3 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 Cytaa3 also occurred: Cytaa3 was mostly either in a reduced state (down to −6.45 μmol/L) or in an oxidised state (up to 6.84 μmol/L) at these low PCr/Pi ratios. The positive predictive value (PPV) of Cytaa3 to predict severe reduction of the PCr/Pi ratio was 42%; the negative PPV was 87%. A similar relation was found for Cytaa3 with histologically determined loss of neurons.
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Abbreviations
- Cytaa 3 :
-
Cytochrome aa3
- HI :
-
Hypoxia-ischaemia
- NIRS :
-
Near infrared spectroscopy
- 31 P-MRS :
-
31Phosphorous magnetic resonance spectroscopy
- PCr/Pi :
-
Phosphocreatin/inorganic phosphate
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Acknowledgements
We thank Tyco Healthcare, Pleasanton, CA, USA, for putting a Nellcor NPB 290 oxymeter at our disposal. We also thank the biotechnicians of the Central Laboratory Animal Institute of the Utrecht University for their enthusiastic help during the experiments. Finally, we thank Kees Braun, Wouter Veldhuis and Prof. K. Nicolay for their help during the MRI/MRS experiments and Prof. P.R. Bär for critically reviewing the manuscript.
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Peeters-Scholte, C., van den Tweel, E., Groenendaal, F. et al. Redox state of near infrared spectroscopy-measured cytochrome aa3 correlates with delayed cerebral energy failure following perinatal hypoxia-ischaemia in the newborn pig. Exp Brain Res 156, 20–26 (2004). https://doi.org/10.1007/s00221-003-1761-5
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DOI: https://doi.org/10.1007/s00221-003-1761-5