Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy.

Near-infrared spectroscopy was used to determine the relationship between the redox state of mitochondrial cytochrome oxidase CuA and haemoglobin oxygenation in the isoflurane-anaesthetized neonatal pig brain. Adding 7% CO2 to the inspired gases increased the total haemoglobin concentration by 8 microM and oxidized CuA by 0.2 microM. Decreasing the inspired oxygen fraction to zero for 90 s dropped the oxyhaemoglobin concentration by 27 microM and reduced CuA by 1.8 microM. However, no change in the CuA redox state was observed until oxyhaemoglobin had decreased by more than 10 microM. The response of the CuA redox state to these stimuli was very similar following 80% replacement of the haemoglobin by a perfluorocarbon blood substitute; this demonstrates that the results in the normal haematocrit were not a spectral artefact due to the high haemoglobin/cytochrome oxidase ratio. We conclude that the large reductions in the CuA redox state during anoxia are caused by a decrease in the rate of oxygen delivery to the cytochrome oxidase oxygen binding site; the small oxidations, however, are likely to reflect the effects of metabolic changes on the redox state of CuA, rather than increases in the rate of oxygen delivery.