Do Slow and Small Oxygen Changes Affect the Cerebral Cytochrome Oxidase Redox State Measured by Near-Infrared Spectroscopy?

Author(s):  
Martin Wolf ◽  
Matthias Keel ◽  
Vera Dietz ◽  
Kurt von Siebenthal ◽  
Hans-Ulrich Bucher ◽  
...  
1999 ◽  
Vol 19 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Chris E. Cooper ◽  
Mark Cope ◽  
Roger Springett ◽  
Philip N. Amess ◽  
Juliet Penrice ◽  
...  

The use of near-infrared spectroscopy to measure noninvasively changes in the 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 that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 μmol/L deoxyhemoglobin, 29 μmol/L oxyhemoglobin, and 1.2 μmol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation 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 measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.


1998 ◽  
Vol 332 (3) ◽  
pp. 627-632 ◽  
Author(s):  
Chris E. COOPER ◽  
David T. DELPY ◽  
Edwin M. NEMOTO

Near-infrared spectroscopy was used to determine the effect of changes in the rate of oxygen delivery to the adult rat brain on the absolute concentrations of oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was determined to be robust to large changes in haemoglobin oxygenation and concentration. By assuming complete haemoglobin deoxygenation and CuA reduction following mechanical ventilation on 100% N2O, the absolute concentration of oxyhaemoglobin (35 µM), deoxyhaemoglobin (27 µM) and the redox state of CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial blood pressure was decreased by exsanguination. When the pressure reached 100 mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin concentration and oxidized CuA levels only fell when cerebral blood volume autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell linearly with decreases in the rate of oxygen delivery to the brain, but the oxidized CuA concentration did not start to fall until this rate was 50% of normal. The results suggest that the brain maintains more than adequate oxygen delivery to mitochondria and that near-infrared spectroscopy may be a good measure of oxygen insufficiency in vivo.


SLEEP ◽  
2003 ◽  
Vol 26 (6) ◽  
pp. 710-716 ◽  
Author(s):  
Anne D McGown ◽  
Himender Makker ◽  
Clare Elwell ◽  
Pippa G Al Rawi ◽  
Arschang Valipour ◽  
...  

PEDIATRICS ◽  
1993 ◽  
Vol 92 (6) ◽  
pp. 883-883
Author(s):  
D. T. DELPY ◽  
M. FERRARI

To the Editor.— In a recent issue of this journal (Pediatrics. 1993;91:414-417), Dr Deborah Hirtz reported on a Workshop on Near Infrared Spectroscopy (NIRS), organized by the National Institute of Neurological Disorders and Stroke (NINDS). NIRS is becoming increasingly accepted as a method for noninvasive monitoring of cerebral hemodynamics and oxygenation in the newborn and recently in the fetus during labor. However, as Dr Hirtz carefully pointed out there are still many technical problems to be solved, and considerable controversy about the quantitation and interpretation of MRS data especially the redox state of cytochrome oxidase.


1997 ◽  
Vol 352 (1354) ◽  
pp. 669-676 ◽  
Author(s):  
Chris E. Cooper ◽  
Roger Springett

Cytochrome oxidase is the terminal electron acceptor of the mitochondrial respiratory chain. It is responsible for the vast majority of oxygen consumption in the body and essential for the efficient generation of cellular ATP. The enzyme contains four redox active metal centres; one of these, the binuclear Cu A centre, has a strong absorbance in the near–infrared that enables it to be detectable in vivo by near–infrared spectroscopy. However, the fact that the concentration of this centre is less than 10 per cent of that of haemoglobin means that its detection is not a trivial matter. Unlike the case with deoxyhaemoglobin and oxyhaemoglobin, concentration changes of the total cytochrome oxidase protein occur very slowly (over days) and are therefore not easily detectable by near–infrared spectroscopy. However, the copper centre rapidly accepts and donates an electron, and can thus change its redox state quickly; this redox change is detectable by near–infrared spectroscopy. Many factors can affect the Cu A redox state in vivo (Cooper et al . 1994), but the most significant is likely to be the molecular oxygen concentration (at low oxygen tensions, electrons build up on Cu A as reduction of oxygen by the enzyme starts to limit the steady–state rate of electron transfer). The factors underlying haemoglobin oxygenation, deoxygenation and blood volume changes are, in general, well understood by the clinicians and physiologists who perform near–infrared spectroscopy measurements. In contrast the factors that control the steady–state redox level of Cu A in cytochrome oxidase are still a matter of active debate, even amongst biochemists studying the isolated enzyme and mitochondria. Coupled with the difficulties of accurate in vivo measurements it is perhaps not surprising that the field of cytochrome oxidase near–infrared spectroscopy has a somewhat chequered past. Too often papers have been written with insufficient information to enable the measurements to be repeated and few attempts have been made to test the algorithms in vivo . In recent years a number of research groups and commercial spectrometer manufacturers have made a concerted attempt to not only say how they are attempting to measure cytochrome oxidase by near–infrared spectroscopy but also to demonstrate that they are really doing so. We applaud these attempts, which in general fall into three areas: first, modelling of data can be performed to determine what problems are likely to derail cytochrome oxidase detection algorithms (Matcher et al . 1995); secondly haemoglobin concentration changes can be made by haemodilution (using saline or artificial blood substitutes) in animals (Tamura 1993) or patients (Skov and Greisen 1994); and thirdly, the cytochrome oxidase redox state can be fixed by the use of mitochondrial inhibitors and then attempts made to cause spurious cytochrome changes by dramatically varying haemoglobin oxygenation, haemoglobin concentration and light scattering (Cooper et al . 1997). We have previously written reviews covering the difficulties of measuring the cytochrome oxidase near–infrared spectroscopy signal in vivo (Cooper et al . 1997) and the factors affecting the oxidation state of cytochrome oxidase Cu A (Cooper et al . 1994). In this article we would like to strike a somewhat more optimistic note: we will stress the usefulness this measurement may have in the clinical environment, as well as describing conditions under which we can have confidence that we are measuring real changes in the Cu A redox state.


1994 ◽  
Vol 22 (4) ◽  
pp. 974-980 ◽  
Author(s):  
C. E. Cooper ◽  
S. J. Matcher ◽  
J. S. Wyatt ◽  
M. Cope ◽  
G. C. Brown ◽  
...  

PEDIATRICS ◽  
1993 ◽  
Vol 91 (2) ◽  
pp. 414-417
Author(s):  
Deborah G. Hirtz

A workshop about near infrared spectroscopy (NIRS), an emerging technology used to measure cerebral oxygenation and blood flow, was sponsored by the Developmental Neurology Branch, Division of Convulsive, Developmental, and Neuromuscular Disorders of the National Institute of Neurological Disorders and Stroke in Bethesda, MD, on March 31 and April 1, 1992. This was an international work-shop designed to bring together experts in the development of this technology with clinical researchers. Topics covered included the history and background of the development of NIRS technology, experimental models for the use of NIRS, clinical experience with NIRS in the neonate and the intrapartum fetus, and current key research issues with regard to technology and clinical use. THE TECHNOLOGY Near infrared spectroscopy is a new application of an existing technology which can provide information about changes in cerebral oxygen saturation, cerebral blood flow and volume, and oxygen utilization in the brain. The technology has been used for a long time to monitor hemoglobin, but only more recently for cytochrome oxidase. It involves the same basic principle used in the pulse oximeter, which uses light in the visible range to detect changes in finger arterial oxygen saturation. The method is based on the fact that light in the near infrared range (700 to 1000 nm) can pass through skin, bone, and other tissues relatively easily and that there are characteristic absorption bands of oxygenated and deoxygenated hemoglobin, and of the mitochondrial enzyme cytochrome oxidase (or cytochrome AA3) in the near infrared range. When the near infrared beam is passed through tissue, a decrease in signal intensity results from the absorbance of the chromophores in the medium.


2012 ◽  
Vol 9 (72) ◽  
pp. 1499-1509 ◽  
Author(s):  
Tracy Moroz ◽  
Murad Banaji ◽  
Nicola J. Robertson ◽  
Chris E. Cooper ◽  
Ilias Tachtsidis

We describe a computational model to simulate measurements from near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) in the piglet brain. Piglets are often subjected to anoxic, hypoxic and ischaemic insults, as experimental models for human neonates. The model aims to help interpret measurements and increase understanding of physiological processes occurring during such insults. It is an extension of a previous model of circulation and mitochondrial metabolism. This was developed to predict NIRS measurements in the brains of healthy adults i.e. concentration changes of oxyhaemoglobin and deoxyhaemoglobin and redox state changes of cytochrome c oxidase (CCO). We altered and enhanced the model to apply to the anaesthetized piglet brain. It now includes metabolites measured by 31 P-MRS, namely phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP). It also includes simple descriptions of glycolysis, lactate dynamics and the tricarboxylic acid (TCA) cycle. The model is described, and its simulations compared with existing measurements from piglets during anoxia. The NIRS and MRS measurements are predicted well, although this requires a reduction in blood pressure autoregulation. Predictions of the cerebral metabolic rate of oxygen consumption (CMRO 2 ) and lactate concentration, which were not measured, are given. Finally, the model is used to investigate hypotheses regarding changes in CCO redox state during anoxia.


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