Does the redox state of cytochrome aa(3) reflect brain energy level during hypoxia? Simultaneous measurements by near infrared spectrophotometry and P-31 nuclear magnetic resonance spectroscopy

We studied cerebral oxygen metabolism during hypoxia to demonstrate whether the redox state of cytochrome aa(3) (cyt.aa(3)), as measured by near infrared spectrophotometry (NIRS), reflects brain energy level. Rats (n = 6) subjected to hypoxia were simultaneously monitored by NIRS and P-31 nuclear magnetic resonance spectroscopy (NMRS). Brain function was evaluated using the electroencephalogram (EEG). After a reduction of the fraction of inspired oxygen (FIO2) from 0.21 to 0.15, we observed a significant increase in reduced cyt.aa(3) (from 16.5% +/- 2.1% to 41.2% +/- 2.8%; P < 0.01), without significant changes in phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) levels. The PCr decreased significantly at a FIO2 of 0.10 (53.8% +/- 6.4% as compared with 97.7% +/- 10.9% at a FIO2 of 0.21; P < 0.05), and reached a minimum at a FIO2 of 0.04. beta-ATP did not change significantly at a FIO2 of 0.10 or 0.08. With a FIO2 of less than 0.08, cyt.aa(3) was almost totally reduced. EEG activity slowed at a FIO2 of 0.08 and became isoelectric at 0.04. Significant correlations were found between the levels of cyt.aa(3) and PCr (P < 0.001, r = 0.83) as well as between cyt.aa(3) and beta-ATP (P < 0.001, r = 0.73) by using the overall values at FIO2 levels from 0 to 1.0. However, no significant correlations were observed among these variables when the FIO2 was less than 0.10. These findings suggest that the increase in reduced cyt.aa(3) reflects brain energy depletion; however, the redox state of cyt.aa(3) will not indicate brain energy depletion during extreme hypoxia because cyt.aa(3) is reduced totally during hypoxia insufficient to deplete intracellular ATP.