scholarly journals Oxygen Dependency of Cerebral Oxidative Phosphorylation in Newborn Piglets

2000 ◽  
Vol 20 (2) ◽  
pp. 280-289 ◽  
Author(s):  
Roger Springett ◽  
Marzena Wylezinska ◽  
Ernest B. Cady ◽  
Mark Cope ◽  
David T. Delpy

Changes in hemoglobin oxygenation and oxidation state of the CuA centre of cytochrome oxidase were measured with full spectral near infrared spectroscopy simultaneously with phosphorus metabolites using nuclear magnetic resonance 31P spectroscopy at high time resolution (10 seconds) during transient anoxia (FiO2 = 0.0 for 105 seconds) in the newborn piglet brain. During the onset of anoxia, there was no change in either phosphocreatine (PCr) concentration or the oxidation state of the CuA centre of cytochrome oxidase until there was a substantial fall in cerebral hemoglobin oxygenation, at which point the CuA centre reduced simultaneously with the decline in PCr. At a later time during the anoxia, intracellular pH decreased rapidly, consistent with a fall in cerebral metabolic rate for O2 and reduced flux through the tricarboxylic acid cycle. The simultaneous reduction of CuA and decline in PCr can be explained in terms of the effects of the falling mitochondrial electrochemical potential. From these observations, it is concluded that, at normoxia, oxidative phosphorylation and the oxidation state of the components of the electron transport chain are independent of cerebral oxygenation and that the reduction in the CuA signal occurs when oxygen tension limits the capacity of oxidative phosphorylation to maintain the phosphorylation potential.

2000 ◽  
Vol 279 (5) ◽  
pp. H2202-H2209 ◽  
Author(s):  
R. Springett ◽  
J. Newman ◽  
M. Cope ◽  
D. T. Delpy

Oxidation changes of the copper A (CuA) center of cytochrome oxidase in the brain were measured during brief anoxic swings at both normocapnia and hypercapnia (arterial Pco 2 ≈55 mmHg). Hypercapnia increased total hemoglobin from 37.5 ± 9.1 to 50.8 ± 12.9 μmol/l (means ± SD; n = 7), increased mean cerebral saturation (SmcO2 ) from 65 ± 4 to 77 ± 3%, and oxidized CuA by 0.43 ± 0.23 μmol/l. During the onset of anoxia, there were no significant changes in the CuA oxidation state until SmcO2 had fallen to 43 ± 5 and 21 ± 6% at normocapnia and hypercapnia, respectively, and the maximum reduction during anoxia was not significantly different at hypercapnia (1.49 ± 0.40 μmol/l) compared with normocapnia (1.53 ± 0.44 μmol/l). Residuals of the least squares fitting algorithm used to convert near-infrared spectra to concentrations are presented and shown to be small compared with the component of attenuation attributed to the CuAsignal. From these observations, we conclude that there is minimal interference between the hemoglobin and CuA signals in this model, the CuA oxidation state is independent of cerebral oxygenation at normoxia, and the oxidation after hypercapnia is not the result of increased cerebral oxygenation.


1997 ◽  
Vol 83 (6) ◽  
pp. 1842-1848 ◽  
Author(s):  
Yoko Hoshi ◽  
Osamu Hazeki ◽  
Yasuyuki Kakihana ◽  
Mamoru Tamura

Hoshi, Yoko, Osamu Hazeki, Yasuyuki Kakihana, and Mamoru Tamura. Redox behavior of cytochrome oxidase in the rat brain measured by near-infrared spectroscopy. J. Appl. Physiol. 83(6): 1842–1848, 1997.—Using near-infrared spectroscopy, we developed a new approach for measuring the redox state of cytochrome oxidase in the brain under normal blood-circulation conditions. Our algorithm does not require the absorption coefficient of cytochrome oxidase, which differs from study to study. We employed this method for evaluation of effects of changes in oxygen delivery on cerebral oxygenation in rats. When fractional inspired oxygen was decreased in a stepwise manner from 100 to <10%, at which point the concentration of oxygenated hemoglobin ([HbO2]) decreased by ∼60%, cytochrome oxidase started to be reduced. Increases in arterial [Formula: see text] under hyperoxic conditions caused an increase in [HbO2], whereas further oxidation of cytochrome oxidase was not observed. The dissociation of the responses of hemogloblin and cytochrome oxidase was also clearly observed after the injection of epinephrine under severely hypoxic conditions; that is, cytochrome oxidase was reoxidized with increasing blood pressure, whereas hemoglobin oxygenation was not changed. These data indicated that oxygen-dependent redox changes in cytochrome oxidase occur only when oxygen delivery is extremely impaired. This is consistent with the in vitro data of our previous study.


1996 ◽  
Vol 11 (3) ◽  
pp. 162-172 ◽  
Author(s):  
Miles Tsuji

Near-infrared spectroscopy (NIRS) is a noninvasive optical monitoring technology that can provide information on relative cerebral oxyhemoglobin, deoxyhemoglobin, and oxidized cytochrome aa3 concentrations. Unlike other bedside clinical monitoring technologies, NIRS provides direct information on cerebral hemoglobin oxygenation and blood volume changes. NIRS recordings have documented changes in cerebral oxygenation in fetuses during labor, critically ill premature infants, cardiopulmonary bypass patients, and adult surgical patients. This information may improve understanding of the causes of brain injury and allow detection of inadequate oxygen delivery before brain injury occurs. Future developments in NIRS technology are likely to produce practical, quantitative bedside monitors of global and regional cerebral oxygenation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yawei Wang ◽  
Binlin Tang ◽  
Lei Long ◽  
Peng Luo ◽  
Wei Xiang ◽  
...  

AbstractPro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.


2007 ◽  
Vol 292 (4) ◽  
pp. R1569-R1576 ◽  
Author(s):  
Laura Bennet ◽  
Vincent Roelfsema ◽  
Justin M. Dean ◽  
Guido Wassink ◽  
Gordon G. Power ◽  
...  

The preterm fetus is capable of surviving prolonged periods of severe hypoxia without neural injury for much longer than at term. To evaluate the hypothesis that regulated suppression of brain metabolism contributes to this remarkable tolerance, we assessed changes in the redox state of cytochrome oxidase (CytOx) relative to cerebral heat production, and cytotoxic edema measured using cerebral impedance, during 25 min of complete umbilical cord occlusion or sham occlusion in fetal sheep at 0.7 gestation. Occlusion was followed by rapid, profound reduction in relative cerebral oxygenation and EEG intensity and an immediate increase in oxidized CytOx, indicating a reduction in electron flow down the mitochondrial electron transfer chain. Confirming rapid suppression of cerebral metabolism there was a loss of the temperature difference between parietal cortex and body at a time when carotid blood flow was maintained at control values. As occlusion continued, severe hypotension/hypoperfusion developed, with a further increase in CytOx levels to a plateau between 8 and 13 min and a progressive rise in cerebral impedance. In conclusion, these data strongly suggest active regulation of cerebral metabolism during the initial response to severe hypoxia, which may help to protect the immature brain from injury.


1999 ◽  
Vol 88 (3) ◽  
pp. 554-558 ◽  
Author(s):  
A. Timothy Lovell ◽  
Huw Owen-Reece ◽  
Clare E. Elwell ◽  
Martin Smith ◽  
John C. Goldstone

2006 ◽  
Vol 59 (3) ◽  
pp. 462-465 ◽  
Author(s):  
Nicole Nagdyman ◽  
Thilo Fleck ◽  
Birgit Bitterling ◽  
Peter Ewert ◽  
Hashim Abdul-Khaliq ◽  
...  

Neonatology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Bi Ze ◽  
Lili Liu ◽  
Ge Sang Yang Jin ◽  
Minna Shan ◽  
Yuehang Geng ◽  
...  

<b><i>Background:</i></b> Accurate detection of cerebral oxygen saturation (rSO<sub>2</sub>) may be useful for neonatal brain injury prevention, and the normal range of rSO<sub>2</sub> of neonates at high altitude remained unclear. <b><i>Objective:</i></b> To compare cerebral rSO<sub>2</sub> and cerebral fractional tissue oxygen extraction (cFTOE) at high-altitude and low-altitude areas in healthy neonates and neonates with underlying diseases. <b><i>Methods:</i></b> 515 neonates from low-altitude areas and 151 from Tibet were enrolled. These neonates were assigned into the normal group, hypoxic-ischemic encephalopathy (HIE) group, and other diseases group. Near-infrared spectroscopy was used to measure rSO<sub>2</sub> in neonates within 24 h after admission. The differences of rSO<sub>2</sub>, pulse oxygen saturation (SpO<sub>2</sub>), and cFTOE levels were compared between neonates from low- and high-altitude areas. <b><i>Results:</i></b> (1) The mean rSO<sub>2</sub> and cFTOE levels in normal neonates from Tibet were 55.0 ± 6.4% and 32.6 ± 8.5%, significantly lower than those from low-altitude areas (<i>p</i> &#x3c; 0.05). (2) At high altitude, neonates with HIE, pneumonia (<i>p</i> &#x3c; 0.05), anemia, and congenital heart disease (<i>p</i> &#x3c; 0.05) have higher cFTOE than healthy neonates. (3) Compared with HIE neonates from plain areas, neonates with HIE at higher altitude had lower cFTOE (<i>p</i> &#x3c; 0.05), while neonates with heart disease in plateau areas had higher cFTOE than those in plain areas (<i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> The rSO<sub>2</sub> and cFTOE levels in normal neonates from high-altitude areas are lower than neonates from the low-altitude areas. Lower cFTOE is possibly because of an increase in blood flow to the brain, and this may be adversely affected by disease states which may increase the risk of brain injury.


1996 ◽  
Vol 81 (3) ◽  
pp. 1174-1183 ◽  
Author(s):  
H. Obrig ◽  
C. Hirth ◽  
J. G. Junge-Hulsing ◽  
C. Doge ◽  
T. Wolf ◽  
...  

We studied cerebral hemodynamic response to a sequential motor task in 56 subjects to investigate the time course and distribution of blood oxygenation changes as monitored by near-infrared spectroscopy (NIRS). To address whether response is modulated by different performance velocities, a group of subjects (n = 12) was examined while performing the motor task at 1, 2, and 3 Hz. The results demonstrate that 1) the NIRS response reflects localized changes in cerebral hemodynamics, 2) the response, consisting of an increase in oxygenated hemoglobin concentration [oxy-Hb] and a decrease in deoxygenated hemoglobin concentration ([deoxy-Hb]), is lateralized and increases in amplitude with higher performance rates, and 3) changes in [oxy-Hb] and [deoxy-Hb] differ in time course. Changes in [oxy-Hb] are biphasic, with a fast initial increase and a pronounced poststimulus undershoot. The stimulus-associated decrease in [deoxy-Hb] is monophasic, and response latency is greater. We conclude that NIRS is able to detect even small changes in cerebral hemodynamic response to functional stimulation.


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