Reduction of cytochrome-c oxidase copper precedes failing cerebral O-2 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 Po-2 (Pti(O2)) and global cerebral O-2 consumption (CMRO(2)) 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 O-2-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 CUA 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 CUA Site of cytochrome-c oxidase is involved in a regulatory adjustment that helps maintain CMR(O2) constant.