Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasivelyin the brain
Ce. Cooper et al., Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasivelyin the brain, ECOL MODEL, 116(2-3), 1999, pp. 27-38
The use of near-infrared spectroscopy to measure noninvasively changes in t
he redox state of cerebral cytochrome oxidase in vivo is controversial. We
therefore tested these measurements using a multiwavelength detector in the
neonatal pig brain. Exchange transfusion with perfluorocarbons revealed th
at the spectrum of cytochrome oxidase in the near-infrared was identical in
the neonatal pig, the adult rat, and in the purified enzyme. Under normoxi
c conditions, the neonatal pig brain contained 15 mu mol/L deoxyhemoglobin,
29 mu mol/L oxyhemoglobin, and 1.2 mu mol/L oxidized cytochrome oxidase. T
he mitochondrial inhibitor cyanide was used to determine whether redox chan
ges in cytochrome oxidase could be detected in the presence of the larger c
erebral hemoglobin concentration. Addition of cyanide induced full reductio
n of cytochrome oxidase in both blooded and bloodless animals. In the blood
ed animals, subsequent anoxia caused large changes in hemoglobin oxygenatio
n and concentration but did not affect the cytochrome oxidase near-infrared
signal. Simultaneous blood oxygenation level-dependent magnetic resonance
imaging measurements showed a good correlation with near-infrared measureme
nts of deoxyhemoglobin concentration. Possible interference in the near-inf
rared measurements from light scattering changes was discounted by simultan
eous measurements of the optical pathlength using the cerebral water absorb
ance as a standard chromophore. We conclude that, under these conditions, n
ear-infrared spectroscopy can accurately measure changes in the cerebral cy
tochrome oxidase redox state.