Reduction of cytochrome-c oxidase copper precedes failing cerebral O₂ utilization in fluorocarbon-perfused cats

We determined the relationship of the low-potential copper (Cu(A)) redox state of cytochrome-c oxidase to the brain tissue PO₂ (Pti(O₂)) and global cerebral O₂ consumption (CMR(O₂)) in vivo. The redox state of cytochrome-c oxidase copper was monitored in perfluorocarbon-exchanged cats under normoxic and graded hypoxic conditions with use of near-infrared spectroscopy. Continuous spectra ranging from 730 to 960 nm were acquired, and the change in copper redox state was assessed by the absorption changes at 830 nm. Pti(O₂) was measured with O₂-sensitive electrodes implanted into the cortex, and CMR(O₂) was determined by sampling arterial and superior sagittal sinus perfusate and by measuring blood flow with radiolabeled microspheres. As Pti(O₂) decreased with hypoxia, the CU(A) of cytochrome-c oxidase became progressively reduced, whereas the CMR(O₂) was unchanged during the initial stages of hypoxia. Only with severe hypoxia, did CMR(O₂) and the amplitude of somatosensory evoked potentials decrease. We conclude that the Cu(A) site of cytochrome-c oxidase is involved in a regulatory adjustment that helps maintain CMR(O₂) constant.