Does the redox state of cytochrome aa3 reflect brain energy level during hypoxia? Simultaneous measurements by near infrared spectrophotometry and 31P nuclear magnetic resonance spectroscopy

Abstract

We studied cerebral oxygen metabolism during hypoxia to demonstrate whether the redox state of cytochrome aa3 (cyt.aa3), as measured by near infrared spectrophotometry (NIRS), reflects brain energy level. Rats (n = 6) subjected to hypoxia were simultaneously monitored by NIRS and 31P 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.aa3 (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.aa3 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.aa3 and PCr (P < 0.001, r = 0.83) as well as between cyt.aa3 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.aa3 reflects brain energy depletion; however, the redox state of cyt.aa3 will not indicate brain energy depletion during extreme hypoxia because cyt.aa3 is reduced totally during hypoxia insufficient to deplete intracellular ATP.