Near-infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia.

The near-IR cytochrome c oxidase (CCO) signal has potential as a clinical marker of changes in mitochondrial oxygen utilization. We examine the CCO signal response to reduced oxygen delivery in the healthy human brain. We induced a reduction in arterial oxygen saturation from baseline levels to 80% in eight healthy adult humans, while minimizing changes in end tidal carbon dioxide tension. We measured changes in the cerebral concentrations of oxidized CCO (Delta[oxCCO]), oxyhemoglobin (Delta[HbO(2)]), and deoxyhemoglobin (Delta[HHb]) using broadband near-IR spectroscopy (NIRS), and estimated changes in cerebral oxygen delivery (ecDO(2)) using pulse oximetry and transcranial Doppler ultrasonography. Results are presented as median (interquartile range). At the nadir of hypoxemia ecDO(2) decreased by 9.2 (5.4 to 12.1)% (p<0.0001), Delta[oxCCO] decreased by 0.24 (0.06 to 0.28) micromoles/l (p<0.01), total hemoglobin concentration increased by 2.83 (2.27 to 4.46) micromoles/l (p<0.0001), and change in hemoglobin difference concentration (Delta[Hbdiff]=Delta[HbO(2)]-Delta[HHb]) decreased by 12.72 (11.32 to 16.34) micromoles/l (p<0.0001). Change in ecDO(2) correlated with Delta[oxCCO] (r=0.78, p<0.001), but not with either change in total hemoglobin concentration or Delta[Hbdiff]. This is the first description of cerebral Delta[oxCCO] during hypoxemia in healthy adults. Studies are ongoing to investigate the clinical relevance of this signal in patients with traumatic brain injury.

[1]  K. Kirk,et al.  Anion channel blockers inhibit swelling-activated anion, cation, and nonelectrolyte transport in HeLa cells. , 1996, The American journal of physiology.

[2]  D. Delpy,et al.  Performance comparison of several published tissue near-infrared spectroscopy algorithms. , 1995, Analytical biochemistry.

[3]  M. Cope,et al.  Utility and Limitations of Near-Infrared Spectroscopy during Cardiopulmonary Bypass in a Piglet Model , 2001, Pediatric Research.

[4]  D. Drabkin,et al.  Metabolism of the hemin chromoproteins. , 1951, Physiological reviews.

[5]  S. Arridge,et al.  Estimation of optical pathlength through tissue from direct time of flight measurement , 1988 .

[6]  D. Delpy,et al.  Use of the water absorption spectrum to quantify tissue chromophore concentration changes in near-infrared spectroscopy. , 1994, Physics in medicine and biology.

[7]  R Springett,et al.  Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[8]  C. Cooper,et al.  The relationship of oxygen delivery to absolute haemoglobin oxygenation and mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared spectroscopy study. , 1998, The Biochemical journal.

[9]  M Crompton,et al.  Cytochrome oxidase content of rat brain during development. , 1991, Biochimica et biophysica acta.

[10]  R. Ordidge,et al.  Use of Mitochondrial Inhibitors to Demonstrate That Cytochrome Oxidase Near-Infrared Spectroscopy Can Measure Mitochondrial Dysfunction Noninvasively in the Brain , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  Himender Makker,et al.  Measurement of changes in cytochrome oxidase redox state during obstructive sleep apnea using near-infrared spectroscopy. , 2003, Sleep.

[12]  B. Ludwig,et al.  Cytochrome c oxidase--structure, function, and physiology of a redox-driven molecular machine. , 2003, Reviews of physiology, biochemistry and pharmacology.

[13]  Hellmuth Obrig,et al.  Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact , 2004, NeuroImage.

[14]  D T Delpy,et al.  Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics. , 1994, Biochemical Society transactions.

[15]  F. Jöbsis Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. , 1977, Science.

[16]  Hiroo Naruse,et al.  Reduction of Cytochrome aa3 Measured by Near-Infrared Spectroscopy Predicts Cerebral Energy Loss in Hypoxic Piglets , 1995, Pediatric Research.

[17]  N. Thakor,et al.  Reduction of cytochrome-c oxidase copper precedes failing cerebral O2 utilization in fluorocarbon-perfused cats. , 1996, The American journal of physiology.

[18]  D F Hanley,et al.  Redox changes in cat brain cytochrome-c oxidase after blood-fluorocarbon exchange. , 1990, The American journal of physiology.

[19]  D. Delpy,et al.  Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain. , 2000, American journal of physiology. Heart and circulatory physiology.

[20]  P. Smielewski,et al.  Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. , 1998, Journal of neurosurgery.

[21]  L. Skov,et al.  Apparent cerebral cytochrome aa3 reduction during cardiopulmonary bypass in hypoxaemic children with congenital heart disease. A critical analysis of in vivo near-infrared spectrophotometric data. , 1994, Physiological measurement.

[22]  D T Delpy,et al.  Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy. , 1998, Biochimica et biophysica acta.

[23]  David T Delpy,et al.  The oxygen dependency of cerebral oxidative metabolism in the newborn piglet studied with 31P NMRS and NIRS. , 2003, Advances in experimental medicine and biology.

[24]  D T Delpy,et al.  Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase. , 1991, Journal of applied physiology.

[25]  B. Reichart,et al.  Postoperative Neuropsychological Dysfunction and Cerebral Oxygenation During Cardiac Surgery , 1995, The Thoracic and cardiovascular surgeon.

[26]  Mamoru Tamura,et al.  Redox behavior of cytochrome oxidase and neurological prognosis in 66 patients who underwent thoracic aortic surgery. , 2002, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[27]  A Villringer,et al.  Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography. , 1997, AJNR. American journal of neuroradiology.