scholarly journals Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury

2018 ◽  
Vol 39 (10) ◽  
pp. 2035-2047 ◽  
Author(s):  
Gemma Bale ◽  
Subhabrata Mitra ◽  
Isabel de Roever ◽  
Magdalena Sokolska ◽  
David Price ◽  
...  

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury.

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 343
Author(s):  
Anna Lavery ◽  
Conrad Ferris

The efficiency with which dairy cows convert dietary nitrogen (N) to milk N is generally low (typically 25%). As a result, much of the N consumed is excreted in manure, from which N can be lost to the environment. Therefore there is increasing pressure to reduce N excretion and improve N use efficiency (NUE) on dairy farms. However, assessing N excretion and NUE on farms is difficult, thus the need to develop proximate measures that can provide accurate estimates of nitrogen utilisation. This review examines a number of these proximate measures. While a strong relationship exists between blood urea N and urinary N excretion, blood sampling is an invasive technique unsuitable for regular herd monitoring. Milk urea N (MUN) can be measured non-invasively, and while strong relationships exist between dietary crude protein and MUN, and MUN and urinary N excretion, the technique has limitations. Direct prediction of NUE using mid-infrared analysis of milk has real potential, while techniques such as near-infrared spectroscopy analysis of faeces and manure have received little attention. Similarly, techniques such as nitrogen isotope analysis, nuclear magnetic resonance spectroscopy of urine, and breath ammonia analysis may all offer potential in the future, but much research is still required.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Thomas W. Engel ◽  
Craig Thomas ◽  
Patrick Medado ◽  
Brian Reed ◽  
Brian J O’Neil

Background: Predicting the outcome of a cardiac arrest (CA) is exceedingly difficult. Previous literature has identified end tidal CO 2 (ETCO 2 ) as a reasonable predictor of both return of spontaneous circulation (ROSC) and futility of resuscitation. Cerebral Oximetry (CerOx) measures the regional O 2 saturation of the frontal lobes of the brain utilizing non-invasive near infrared spectroscopy and has been correlated with cerebral oxygenation. Objectives: The objective of this study is to compare measurement of ETCO 2 and CerOx to predict ROSC during both out of hospital cardiac arrests (OHCA) and emergency department cardiac arrests (EDCA). Methods: We conducted an IRB approved, prospective study on a convenience sample of patients suffering from OHCA and EDCA. Patients were monitored with ETCO 2 and CerOx simultaneously while CPR was being performed in the ED. All patients were evaluated to predict ROSC by six parameters utilizing area under the curve (AUC) values. Data was analyzed using logistic regression modeling. AUCs were compared using the Delong, Delong, and Clarke-Pearson method. Results: Overall, we analyzed 176 patients. The mean age was 62.3 ± 14.4 . 116 (66.7%)were witnessed arrest with 93 (53.8%) having received immediate CPR. The average downtime from EMS call to ED arrival was 39 minutes. The initial rhythm in these patients was 56 (31.8%) asystole, 49 (27.8%) PEA, 45 (25.6%) VF/VT, and non-shockable rhythm in 26 (14.8%) . ROSC was achieved in 46 (26.1%) of patients. The analysis of the individual variable prediction of ROSC, revealed: first value [CerOx AUC = 0.554 p = 0.1143 ; ETCO 2 AUC = 0.533, p = 0.3981], maximum value [CerOx AUC = 0.778 p < 0.0001; ETCO 2 AUC = 0.616 p = 0.0849 ], trend over the last 5 minutes [CerOx AUC = 0.821 p < 0.0001 ; ETCO 2 AUC = 0.744 p = 0.7354 ], delta from first to last value [CerOx AUC = 0.859 p < 0.0001 ; ETCO 2 AUC = 0.734 p = < 0.0001 ], average value of the penultimate minute of resuscitation [CerOx AUC = 0.814 p <0.0001 ; ETCO2 AUC = 0.759 p = 0.0003 ], and average value of the final minute of the resuscitation [CerOx AUC = 0.886 p < 0.0001 ; ETCO2 AUC = 0.770 p = 0.0001}. Conclusion: Our data shows that both ETCO2 and rSO2 are good predictors of ROSC. We found CerOx superior to ETCO 2 in predicting ROSC.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 564
Author(s):  
Almir Bitencourt ◽  
Varadan Sevilimedu ◽  
Elizabeth A. Morris ◽  
Katja Pinker ◽  
Sunitha B. Thakur

Altered metabolism including lipids is an emerging hallmark of breast cancer. The purpose of this study was to investigate if breast cancers exhibit different magnetic resonance spectroscopy (MRS)-based lipid composition than normal fibroglandular tissue (FGT). MRS spectra, using the stimulated echo acquisition mode sequence, were collected with a 3T scanner from patients with suspicious lesions and contralateral normal tissue. Fat peaks at 1.3 + 1.6 ppm (L13 + L16), 2.1 + 2.3 ppm (L21 + L23), 2.8 ppm (L28), 4.1 + 4.3 ppm (L41 + L43), and 5.2 + 5.3 ppm (L52 + L53) were quantified using LCModel software. The saturation index (SI), number of double bods (NBD), mono and polyunsaturated fatty acids (MUFA and PUFA), and mean chain length (MCL) were also computed. Results showed that mean concentrations of all lipid metabolites and PUFA were significantly lower in tumors compared with that of normal FGT (p ≤ 0.002 and 0.04, respectively). The measure best separating normal and tumor tissues after adjusting with multivariable analysis was L21 + L23, which yielded an area under the curve of 0.87 (95% CI: 0.75–0.98). Similar results were obtained between HER2 positive versus HER2 negative tumors. Hence, MRS-based lipid measurements may serve as independent variables in a multivariate approach to increase the specificity of breast cancer characterization.


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

2010 ◽  
Vol 108 (6) ◽  
pp. 1472-1478 ◽  
Author(s):  
Patrice Brassard ◽  
Thomas Seifert ◽  
Mads Wissenberg ◽  
Peter M. Jensen ◽  
Christian K. Hansen ◽  
...  

Whether sympathetic activity influences cerebral blood flow (CBF) and oxygenation remains controversial. The influence of sympathetic activity on CBF and oxygenation was evaluated by the effect of phenylephrine on middle cerebral artery (MCA) mean flow velocity ( Vmean) and the near-infrared spectroscopy-derived frontal lobe oxygenation (ScO2) at rest and during exercise. At rest, nine healthy male subjects received bolus injections of phenylephrine (0.1, 0.25, and 0.4 mg), and changes in mean arterial pressure (MAP), MCA Vmean, internal jugular venous O2 saturation (SjvO2), ScO2, and arterial Pco2 (PaCO2) were measured and the cerebral metabolic rate for O2 (CMRO2) was calculated. In randomized order, a bolus of saline or 0.3 mg of phenylephrine was then injected during semisupine cycling, eliciting a low (∼110 beats/min) or a high (∼150 beats/min) heart rate. At rest, MAP and MCA Vmean increased ∼20% ( P < 0.001) and ∼10% ( P < 0.001 for 0.25 mg of phenylephrine and P < 0.05 for 0.4 mg of phenylephrine), respectively. ScO2 then decreased ∼7% ( P < 0.001). Phenylephrine had no effect on SjvO2, PaCO2, or CMRO2. MAP increased after the administration of phenylephrine during low-intensity exercise (∼15%), but this was attenuated (∼10%) during high-intensity exercise ( P < 0.001). The reduction in ScO2 after administration of phenylephrine was attenuated during low-intensity exercise (−5%, P < 0.001) and abolished during high-intensity exercise (−3%, P = not significant), where PaCO2 decreased 7% ( P < 0.05) and CMRO2 increased 17% ( P < 0.05). These results suggest that the administration of phenylephrine reduced ScO2 but that the increased cerebral metabolism needed for moderately intense exercise eliminated that effect.


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

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