Changes In PO2 Research Articles

19F Oximetry with semifluorinated alkanes

This work examines the variation of longitudinal relaxation rate R1(= 1/T1) of the 19F-CF3-resonance of semifluorinated alkanes (SFAs) with oxygen tension (pO2), temperature (T) and pH in vitro. Contrary to their related perfluorocarbons (PFCs), SFA are amphiphilic and facilitate stable emulsions, a prerequisite for clinical use. A linear relationship between R1 and pO2 was confirmed for the observed SFAs at different temperatures. Using a standard saturation recovery sequence, T1 has been successfully measured using fluorine 19F-MRI with a self-constructed birdcage resonator at 9.4 T. A calibration curve to calculate pO2 depending on T and R1 was found for each SFA used. In contrast to the commonly used PFC, SFAs are less sensitive to changes in pO2, but more sensitive to changes in temperature. The influence of pH to R1 was found to be negligible.

Oxygen equilibration kinetics of mixed-conducting perovskites BSCF, LSCF, and PSCF at 900 °C determined by electrical conductivity relaxation

For an application of mixed ionic-electronic conducting (MIEC) perovskite oxides, e.g., as solid oxide fuel cell (SOFC) cathodes, as high-temperature gas sensors or as oxygen-transport membrane (OTM) materials, the kinetics of oxygen transport is of fundamental importance.A common setup for the determination of the chemical diffusion coefficient Dδ and the surface exchange coefficient kδ is the electrical conductivity relaxation (ECR) method where the conductivity response of an MIEC sample is measured after the ambient oxygen partial pressure pO2 has been abruptly changed using different gas mixtures. In the present study, however, a closed tubular zirconia “oxygen pump” setup was used which facilitates precise pO2 control in a closed sample space with a high resolution at temperatures above 700°C in atmospheres ranging from pure oxygen continuously down to pO2=10−18bar. Reasonably fast pO2 changes enable an application of the ECR technique on MIEC oxides down to lower partial pressures not easily accessible with gas mixtures.The oxygen transport parameters of dense ceramic bulk samples of Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), La0.58Sr0.4Co0.2Fe0.8O3-δ (LSCF), and Pr0.58Sr0.4Co0.2Fe0.8O3-δ (PSCF) have been studied as a function of temperature (800 and 900°C) in the range between 10−6≤pO2/bar≤0.21. The Dδ and kδ values obtained for LSCF at 800°C are in good agreement with values from literature, proving the usability of the setup for ECR measurements. For BSCF, LSCF, and PSCF, Dδ and kδ values could be determined for the first time at 900°C as a function of pO2.

Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I Signaling

O2 sensing is essential for mammalian homeostasis. Peripheral chemoreceptors such as the carotid body (CB) contain cells with O2-sensitive K(+) channels, which are inhibited by hypoxia to trigger fast adaptive cardiorespiratory reflexes. How variations of O2 tension (PO2) are detected and the mechanisms whereby these changes are conveyed to membrane ion channels have remained elusive. We have studied acute O2 sensing in conditional knockout mice lacking mitochondrial complex I (MCI) genes. We inactivated Ndufs2, which encodes a protein that participates in ubiquinone binding. Ndufs2-null mice lose the hyperventilatory response to hypoxia, although they respond to hypercapnia. Ndufs2-deficient CB cells have normal functions and ATP content but are insensitive to changes in PO2. Our data suggest that chemoreceptor cells have a specialized succinate-dependent metabolism that induces an MCI state during hypoxia, characterized by the production of reactive oxygen species and accumulation of reduced pyridine nucleotides, which signal neighboring K(+) channels.

A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus

The mammalian homeostatic oxygen sensing system (HOSS) initiates changes in vascular tone, respiration, and neurosecretion that optimize oxygen uptake and tissue oxygen delivery within seconds of detecting altered environmental or arterial PO2. The HOSS includes carotid body type 1 cells, adrenomedullary cells, neuroepithelial bodies, and smooth muscle cells (SMCs) in pulmonary arteries (PAs), ductus arteriosus (DA), and fetoplacental arteries. Hypoxic pulmonary vasoconstriction (HPV) optimizes ventilation-perfusion matching. In utero, HPV diverts placentally oxygenated blood from the non-ventilated lung through the DA. At birth, increased alveolar and arterial oxygen tension dilates the pulmonary vasculature and constricts the DA, respectively, thereby transitioning the newborn to an air-breathing organism. Though modulated by endothelial-derived relaxing and constricting factors, O2 sensing is intrinsic to PASMCs and DASMCs. Within the SMC's dynamic mitochondrial network, changes in PO2 alter the reduction-oxidation state of redox couples (NAD(+)/NADH, NADP(+)/NADPH) and the production of reactive oxygen species, ROS (e.g., H2O2), by complexes I and III of the electron transport chain (ETC). ROS and redox couples regulate ion channels, transporters, and enzymes, changing intracellular calcium [Ca(2+)]i and calcium sensitivity and eliciting homeostatic responses to hypoxia. In PASMCs, hypoxia inhibits ROS production and reduces redox couples, thereby inhibiting O2-sensitive voltage-gated potassium (Kv) channels, depolarizing the plasma membrane, activating voltage-gated calcium channels (CaL), increasing [Ca(2+)]i, and causing vasoconstriction. In DASMCs, elevated PO2 causes mitochondrial fission, increasing ETC complex I activity and ROS production. The DASMC's downstream response to elevated PO2 (Kv channel inhibition, CaL activation, increased [Ca(2+)]i, and rho kinase activation) is similar to the PASMC's hypoxic response. Impaired O2 sensing contributes to human diseases, including pulmonary arterial hypertension and patent DA.

Gone fission: an asymptomatic STAT2 mutation elongates mitochondria and causes human disease following viral infection.

This scientific commentary refers to ‘Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission’, by Shahni et al. (doi:10.1093/brain/awv182). Mitochondria exist in dynamic networks, which undergo rapid cycles of fission (division) and fusion (union). The adaptive roles of fission and fusion depend on the state of the cell and include: mitotic fission (mitochondrial division coordinated with mitosis supporting equitable distribution of mitochondria to daughter cells); mitophagic fission (mitochondrial division isolating dysfunctional portions of the organelle for elimination by mitophagy, thereby maintaining mitochondrial quality control); apoptotic fission (a prelude to apoptosis); and oxygen-sensitive fission [mitochondrial division occurring in response to a change in PO2 which modulates the production of reactive oxygen species (ROS)], as reviewed in Archer (2013). Mitochondrial fusion regulates mitochondrial calcium, mitochondrial metabolism and cell cycle progression (Archer, 2013). In this issue of Brain, Shahni et al. (2015) identify signal transducer and activator of transcription 2 (STAT2) as a novel activator of dynamin-related protein 1 (DRP1)-induced fission and report that a clinically asymptomatic STAT2 mutation in three patients predisposed them to develop severe, multiorgan dysfunction associated with impaired mitochondrial fission, subsequent to receiving the measles-mumps-rubella (MMR) vaccination. The patients included siblings aged 12 and 13 months and a previously reported, unrelated subject diagnosed at 18 months of age (Hambleton et al. , 2013). All patients developed fever, and amongst the three of them showed other abnormalities including: conjunctivitis, lymphadenopathy, a sepsis-like syndrome, seizures, hepatitis and pneumonitis. The major mediators of mitochondrial fusion are GTPases in the outer mitochondrial membrane [mitofusin 1 (MFN1) and mitofusin 2 (MFN2)], and the inner mitochondrial membrane protein optic atrophy 1 (OPA1). Fission is regulated by a single GTPase, DRP1. On activation, DRP1 is recruited from the cytosol to the mitochondrial outer membrane where it …

Optimized real-time monitoring of glutathione redox status in single pyramidal neurons in organotypic hippocampal slices during oxygen-glucose deprivation and reperfusion.

A redox-sensitive Grx1-roGFP2 fusion protein was introduced by transfection into single pyramidal neurons in the CA1 subfield of organotypic hippocampal slice cultures (OHSCs). We assessed changes in the GSH system in neuronal cytoplasm and mitochondria during oxygen-glucose deprivation and reperfusion (OGD/RP), an in vitro model of stroke. Pyramidal cells in a narrow range of depths below the surface of the OHSC were transfected by gene gun or single-cell electroporation with cyto- or mito-Grx1-roGFP2. To mimic the conditions of acute stroke, we developed an optimized superfusion system with the capability of rapid and reproducible exchange of the solution bathing the OHSCs. Measurements of pO2 as a function of tissue depth show that in the region containing the transfected cells, the pO2 is well-controlled. We also found that the pO2 changes on the same time scale as changes in intracranial pressure, cerebral blood flow, and pO2 during acute stroke. Determining the reduction potential, EGSH, from the ratiometric fluorescence signal requires an absolute intensity measurement during calibration of the Grx1-roGFP2. Using the signal from cotransfected tdTomato as an internal standard during calibration improves quantitative measurements of Grx1-roGFP2 redox status and allows EGSH to be determined. EGSH becomes more reducing during OGD and more oxidizing during RP in mitochondria while changes in cytoplasm are not significant compared with controls.

Functional Oxygen Sensitivity of Astrocytes.

In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 . Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial respiration, leading to mitochondrial depolarization, production of free radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i increases in astrocytes trigger fusion of vesicular compartments containing ATP. Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or targeted astrocyte-specific expression of tetanus toxin light chain (to interfere with vesicular release mechanisms) within the brainstem respiratory rhythm-generating circuits reveals the fundamental physiological role of astroglial oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this mechanism increases breathing activity even in the absence of peripheral chemoreceptor oxygen sensing. These results demonstrate that astrocytes are functionally specialized CNS oxygen sensors tuned for rapid detection of physiological changes in brain oxygenation. Significance statement: Most, if not all, animal cells possess mechanisms that allow them to detect decreases in oxygen availability leading to slow-timescale, adaptive changes in gene expression and cell physiology. To date, only two types of mammalian cells have been demonstrated to be specialized for rapid functional oxygen sensing: glomus cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate breathing when oxygenation of the arterial blood decreases; and pulmonary arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction to limit perfusion of poorly ventilated regions of the lungs. Results of the present study suggest that there is another specialized oxygen-sensitive cell type in the body, the astrocyte, that is tuned for rapid detection of physiological changes in brain oxygenation.

Effect Of Exercise On Interstitial PO2 And Contractile Function In The Diaphragm Of Diabetic Rats

Type I diabetes in rats causes structural, functional, and metabolic changes in skeletal muscle which impair contractile function and alter the balance between oxygen delivery (QO2) and oxygen consumption (VO2), as reflected by changes in interstitial PO2 (PiO2). Exercise improves the QO2 to VO2 balance and muscle function. The diaphragm is also affected by diabetes however the impact of exercise training on QO2 to VO2 balance and contractile function in diabetic rats is not well described. PURPOSE: To determine the effect of low intensity exercise training on PiO2 at the onset of contractions compared to sedentary diabetic rats, and to determine whether exercise training will attenuate the diabetes-induced deficits in contractile function. METHODS: Female Sprague-Dawley rats (n=33, 257 ± 2 g) were randomly assigned to control (C, 10), diabetic (D, 9), or exercise trained diabetic groups (DET, 14). Diabetes (streptozotocin, 50 mg/kg) was confirmed by urine glucose (>2000 mg/dl). After the onset of diabetes, the DET rats began an 8 wk low intensity treadmill training program. Rats were anesthetized (pentobarbital sodium, 50 mg/kg) and the abdominal surface of the costal diaphragm was exposed. The phrenic nerves were transected and electrodes were placed in the ventral and dorsal costal diaphragm to elicit contractions at 1 and 4 Hz (6V). PiO2 (phosphorescence quenching) and contractile function were measured simultaneously in the medial costal diaphragm. RESULTS: The D group had reduced body (C, 297 ± 9; D, 254 ± 9 g; P≤.05) and diaphragm weight (C, 148 ± 10; D, 113 ± 6 mg; P≤.05). Absolute twitch tension (g) and rate of tension change (dT/dt, g/s) were reduced in D compared to C (P≤0.05). Twitch tension normalized per gram of tissue (N/g) was not different in C and D, while dT/dt (N/g.s) was lower in the D group. Training did not improve body, diaphragm weight, (262 ± 6 g; 131 ± 8 mg) or contractile function. Baseline PiO2 (C, 62 ± 5; D, 61 ± 3; DET, 62 ± 5 mmHg) and mean response time (C, 19 ± 2; D, 16 ± 3; DET, 15 ± 2 s) were similar in the three groups. CONCLUSIONS: The decreases in body and diaphragm weights are characteristic of insulin-dependent diabetes. The D diaphragm produced less absolute tension, and training did not improve contractile function. PiO2 kinetics was similar in all three groups, suggesting that chronic diaphragm activity may be sufficient to maintain the normal QO2 to VO2 balance. (Supported by the Graduate Program Committee, KCOM-ATSU)

Effects Of Enalapril On Interstitial PO2 And Contractile Function In The Edl Of Diabetic Rats

Angiotensin converting enzyme inhibitors (ACEi) are standard of care for Type I diabetics. ACEi play a role in preventing diseases such as heart failure, kidney disease, and diabetic neuropathy. Diabetes causes changes within skeletal muscle that alter the balance between oxygen delivery (QO2) and oxygen consumption (VO2) as reflected by changes in the interstitial PO2 (PiO2). PURPOSE: To determine if treatment with the ACEi enalapril would attenuate the effects of diabetes on PiO2 and contractile function in the rat extensor digitorum longus muscle (EDL). METHODS: Female Sprague-Dawley rats (n=33, 282 ± 3 g) were randomly assigned to control (C, 11), diabetic (D, 11), or enalapril-treated diabetic groups (E, 11). Diabetes was induced using streptozotocin (50 mg/kg) and confirmed by urine glucose (>2000 mg/dl). The E group then began a 7 wk treatment regimen of enalapril in their drinking water (15 mg/kg/d). Rats were anesthetized (sodium pentobarbital, 50 mg/kg) and the EDL was exposed and connected to a muscle tension analyzer. PiO2 (phosphorescent quenching) and contractile function were assessed at rest and during the transition to steady-state contractions (1 Hz, 6V). RESULTS: D rats weighed less than C (D, 266 ± 5 vs 305 ± 8 g) and showed atrophy of the EDL (127 ± 10 vs 177 ± 8 mg), and E rats were not different from D (285 ± 10 g and 138 ± 9 mg). Enalapril resulted in a marked reduction in mean arterial pressure (C, 116 ± 2; D, 108 ± 2; E, 91 ± 2 mmHg). Resting PiO2 was lower in D compared to C (24 ± 1 vs. 28 ± 1 mmHg). At the onset of contractions, PiO2 fell more rapidly in D than C (i.e., faster on-kinetics) as reflected by the shorter mean response time (13 ± 2 vs. 22 ± 2 s). Resting PiO2 in E (30 ± 2 mmHg) was greater than D, and on-kinetics were slower (MRT, 19 ± 2 s) and not different from C. Peak twitch tension (per muscle mass) was greater in D compared to C (1.78 ± 0.04 vs. 1.36 ± 0.04 N/g), while twitch tension in E was similar to D (1.88 ± 0.04 N/g). Fatigue was greater in both the D and E groups relative to C (C, 5 ± 1; D, 12 ± 1, E, 11 ± 1 %). CONCLUSIONS: These results confirm previous reports of a diabetes-induced imbalance between QO2 and VO2 at rest and during contractions in diabetic rats. ACEi treatment prevented these changes but did not improve contractile function or fatigue resistance. These results support the notion that ACEi treatment improves the matching of QO2 and VO2 to skeletal muscle. (Supported by Graduate Program Committee, KCOM-ATSU.)

Optimization of blood gas analysis in intensive care units : Reduction of preanalytical errors and improvement of workflow

Point of care testing with blood gas analysis (BGA) is an important factor for intensive care medicine. Continuous efforts to optimize workflow, improve safety for the staff and avoid preanalytical mistakes are important and should reflect quality management standards. In a prospective observational study it was investigated whether the implementation of a new system for BGA using labeled syringes and automated processing of the specimens leads to improvements compared to the previously used procedure. In a 4-week test period the time until receiving the final results of the BGA with the standard method used in the clinical routine (control group) was compared to the results in a second 4-week test period using the new labeled syringes and automated processing of the specimens (intervention group). In addition, preanalytical mistakes with both systems were checked during routine daily use. Finally, it was investigated whether a delay of 10 min between taking and analyzing the blood samples alters the results of the BGA. Preanalytical errors were frequently observed in the control group where non-deaerated samples were recorded in 87.3 % but in the intervention group almost all samples (98.9 %) were correctly deaerated. Insufficient homogenization due to omission of manual pivoting was seen in 83.2 % in the control group and in 89.9 % in the intervention group; however, in the intervention group the samples were homogenized automatically during the further analytical process. Although a survey among the staff revealed a high acceptance of the new system and a subjective improvement of workflow, a measurable gain in time after conversion to the new procedure could not be seen. The mean time needed for a complete analysis process until receiving the final results was 244 s in the intervention group and 201 s in the control group. A 10-min delay between taking and analyzing the blood samples led to a significant and clinically relevant elevation of the values for partial pressure of oxygen (pO2) in both groups compared to the results when analyzing the samples immediately (118.4 vs. 148.6 mmHg in the control group and 115.3 vs. 123.7 mmHg in the intervention group). When using standard syringes the partial pressure of carbon dioxide (pCO2) was significantly lower (40.5 vs. 38.3 mmHg) whereas no alterations were seen when using the labeled syringes. The implementation of a new BGA system with labeled syringes and automated processing of the specimens was possible without any difficulties under daily clinical routine conditions in this 10-bed intensive care unit (ICU). A gain of time could not be measured but a reduction in preanalytical errors using the labeled syringes with automated processing was found. Delayed analysis of blood samples can lead to significant changes in pO2 and pCO2 depending on the type of syringe used.

Spinal Oxygen Sensors (SOS) drive sympathetic activity that precedes, predicts and outlives phrenic gasps during hypoxia in the absence of the brainstem

An essential role of the cardiorespiratory system is to ensure the brain is adequately oxygenated. This is achieved in part by responding to hypoxia with increases in peripheral vasoconstriction, heart rate and blood pressure through activation of the sympathetic nervous system. Here we report a novel spinal oxygen sensor (SOS) that can detect and respond to changes in PO2 by increasing sympathetic activity. Using an isolated artificially perfused thoracic-cervical spinal cord preparation, we show that these oxygen sensors are cable of causing sympathetic activity in response to hypoxia which precede, predicts and outlive phrenic gasps. We further confirmed the presence of SOS's in an anesthetized, artificially ventilated in vivo preparation, by demonstrating that sympathetic nerve activity increases during a hypoxic bout after carotid body denervation and complete spinal cord transaction. Given the sympathetic nervous system modulates blood flow through almost every end organ and blood vessel in the body, these data suggest SOS's play an important role in ensuring oxygenation of the brain and initiating emergency responses to hypoxia. This work was funded by CIHR and AIHS.

Intra-breath arterial oxygen oscillations detected by a fast oxygen sensor in an animal model of acute respiratory distress syndrome

BackgroundThere is considerable interest in oxygen partial pressure (Po2) monitoring in physiology, and in tracking Po2 changes dynamically when it varies rapidly. For example, arterial Po2 () can vary within the respiratory cycle in cyclical atelectasis (CA), where is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these oscillations could become a useful diagnostic tool of CA during acute respiratory distress syndrome (ARDS).MethodsWe developed a fibreoptic Po2 sensor (<200 µm diameter), suitable for human use, that has a fast response time, and can measure Po2 continuously in blood. By altering the inspired fraction of oxygen () from 21 to 100% in four healthy animal models, we determined the linearity of the sensor's signal over a wide range of values in vivo. We also hypothesized that the sensor could measure rapid intra-breath oscillations in a large animal model of ARDS.ResultsIn the healthy animal models, responses to changes in were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected oscillations, also at clinically relevant levels close to 9 kPa.ConclusionsWe conclude that these fibreoptic sensors have the potential to become a diagnostic tool for CA in ARDS.

Telemetry‐based Recording of Renal Cortex Oxygenation During Endogenous RAS Activation: Preliminary Observations

Upon feeding of the food additive indole‐3‐carbinol (I3C) the liver of Cyp1A1Ren2 transgenic rats produces high levels of renin which leads to hypertension and tissue damage in the kidney. We hypothesized that endogenous RAS activation in this model would be associated with renal hypoxia. Using a new technology that enables the telemetric recording of intra‐renal tissue oxygen pressure (PO2) in conscious, free roaming animals, we here report preliminary observations on renal cortical PO2 changes during endogenous RAS activation. 1 week after implantation of the electrodes the relative change in renal cortex PO2 during bouts of 3 days of endogenous activation of RAS by feeding an 0.3% or 0.6% I3C containing diet (n=5) were recorded. 3±2 days after start of the 0.6% I3C diet, s.c. bolus infusions of valsartan/losartan (20/30 mg/kg) were administered. During 0.3% and 0.6% I3C feeding, renal PO2 levels fell to 75±7 and 63±13% from baseline values (mean±SD), with a nadir after 25±5 hours. Exogenous blockade of the angiotensin‐II receptor increased oxygen levels within 14±3 min to 98±38% of baseline values (mean±SD). These data suggest that oxygen levels in the renal cortex decrease rapidly during the onset of endogenous RAS hyperactivation. The effect is mediated by AT1‐receptor activation and may precede the known development of systemic hypertension and renal injury in this model.

Monitoring Combretastatin A4-induced tumor hypoxia and hemodynamic changes using endogenous MR contrast and DCE-MRI.

To benchmark MOBILE (Mapping of Oxygen By Imaging Lipid relaxation Enhancement), a recent noninvasive MR method of mapping changes in tumor hypoxia, electron paramagnetic resonance (EPR) oximetry, and dynamic contrast-enhanced MRI (DCE-MRI) as biomarkers of changes in tumor hemodynamics induced by the antivascular agent combretastatin A4 (CA4). NT2 and MDA-MB-231 mammary tumors were implanted subcutaneously in FVB/N and nude NMRI mice. Mice received 100 mg/kg of CA4 intraperitoneally 3 hr before imaging. The MOBILE sequence (assessing R1 of lipids) and the DCE sequence (assessing K(trans) hemodynamic parameter), were assessed on different cohorts. pO2 changes were confirmed on matching tumors using EPR oximetry consecutive to the MOBILE sequence. Changes in tumor vasculature were assessed using immunohistology consecutive to DCE-MRI studies. Administration of CA4 induced a significant decrease in lipids R1 (P = 0.0273) on pooled tumor models and a reduction in tumor pO2 measured by EPR oximetry. DCE-MRI also exhibited a significant drop of K(trans) (P < 0.01) that was confirmed by immunohistology. MOBILE was identified as a marker to follow a decrease in oxygenation induced by CA4. However, DCE-MRI showed a higher dynamic range to follow changes in tumor hemodynamics induced by CA4.

Deep-tissue oxygen monitoring in the brain of rabbits for stroke research.

The primary event in the ischemic stroke is a rapid decline in the oxygen levels after the loss of blood flow in specific areas of the brain. Subsequent pathological processes results in a central core area of severely ischemic tissue surrounded by a region of moderate ischemic tissue (penumbra) with a preserved cellular metabolism. The outcome of an ischemic stroke depends on the size of the infarct core and the potential to salvage the cells in the penumbra, which is hypoperfused, and therefore, at risk of infarction but still viable. Such viable penumbral tissue can be rescued by quick interventions that can increase oxygen levels or slow metabolism in the ischemic area to minimize oxidative injury on reperfusion. Several strategies have been investigated to rescue ischemic tissue using experimental models, especially rodents, but largely failed in subsequent clinical trials. The rabbit model of ischemic stroke using embolic clot is a promising model for developing effective strategies. This model first led to the prediction of the clinical response of recombinant tissue-type plasminogen activator to restore blood flow in patients.1 The drug is currently recommended for administration within 3 hours for best outcomes and has also shown modest benefit when administered within 4.5 to 6 hours of clinical onset.2 The rabbit model of embolic clot is now considered as a pertinent model for translational research by the Stroke Therapy Academic Industry Roundtable recommendations.3 To rationally develop effectual therapies, it is important to understand the effect of ischemic stroke on oxygen levels (partial pressure of oxygen [pO2]) in the regions directly affected by the pathology, as well as contralateral regions of the rabbit brain. The potential changes in tissue po2 of contralateral regions may provide crucial information on adaptive response, if any, of the brain …

Inter- and intra-annual variations of pCO2 and pO2 in a freshwater subtropical coastal lake

Inland waters emit significant amounts of carbon dioxide to the atmosphere, but tropical and subtropical lakes are underrepresented in current assessments. Here we present results of a 6-year study of the dynamics of surface partial pressures of carbon dioxide and oxygen (pCO2 and pO2) in a subtropical lake, Lake Peri, Brazil, to determine how temperature, rainfall, and wind moderate surface concentrations. Both pCO2 and pO2 tended to increase during the transitions between seasons when rainfall increased, with pCO2 averaging 2.5–3-fold higher than atmospheric values. Occasionally during autumn/winter, pCO2 similarly increased and pO2 decreased. We infer that the increases in both gases during the transition periods resulted from increasing inputs of allochthonous material into the lake. Those in winter resulted from near-bottom intrusions that intermittently reach the depth of measurement. In autumn/winter, pCO2 was 3-fold higher (average 1700 μatm) compared to spring/summer (550 μatm), whereas changes in pO2 did not have a clear seasonal pattern. Overall median net CO2 evasion was 11 mg C m−2 d−1. Variability in the extent of rainfall and the associated high intra- and inter-annual variability in CO2 and CO2 emissions are in part controlled by atmospheric processes related to the South American Monsoon System and to El Niño Southern Oscillation cycles.

Modulation of the LKB1-AMPK Signalling Pathway Underpins Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension.

Perhaps the defining characteristic of pulmonary arteries is the process of hypoxic pulmonary vasoconstriction (HPV) which, under physiological conditions, supports ventilation-perfusion matching in the lung by diverting blood flow away from oxygen deprived areas of the lung to oxygen rich regions. However, when alveolar hypoxia is more widespread, either at altitude or with disease (e.g., cystic fibrosis), HPV may lead to hypoxic pulmonary hypertension. HPV is driven by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and endothelial cells, which are acutely sensitive to relatively small changes in pO2 and have evolved to monitor oxygen supply and thus address ventilation-perfusion mismatch. There is now a consensus that the inhibition by hypoxia of mitochondrial oxidative phosphorylation represents a key step towards the induction of HPV, but the precise nature of the signalling pathway(s) engaged thereafter remains open to debate. We will consider the role of the AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), an upstream kinase through which AMPK is intimately coupled to changes in oxygen supply via mitochondrial metabolism. A growing body of evidence, from our laboratory and others, suggests that modulation of the LKB1-AMPK signalling pathway underpins both hypoxic pulmonary vasoconstriction and the development of pulmonary hypertension.

Qualification of a noninvasive magnetic resonance imaging biomarker to assess tumor oxygenation.

Although hypoxia has been long recognized as a crucial factor impairing tumor response in many therapeutic schemes, atraumatic and reliable methods of individually quantifying tumor oxygenation are still lacking in day-to-day clinical practice. The aim of this work was to investigate the potentially quantitative properties of our recently described noninvasive magnetic resonance (MR) technique "MOBILE" (mapping of oxygen by imaging lipids relaxation enhancement) and to qualify this endogenous contrast as a tumor hypoxia marker. The "MOBILE" technique, which assesses the longitudinal MR relaxation rate, R1, of lipid protons, was benchmarked with the parent technique which assesses the global (or water) R1, in response to a hyperoxic challenge (carbogen breathing) and to a hypoxic challenge (combretastatin A4) in MDA-MB-231 xenografts and in NT2 mammary tumors. Electron paramagnetic resonance (EPR) oximetry was used to quantitatively assess the tumor pO2 in matching tumors longitudinally. Our study evidenced that (i) positive and negative changes in tumor oxygenation can be detected using MOBILE; (ii) a change in the R1 of lipids is positively correlated with a change in the tumor pO2 (P = 0.0217, r = 0.5097); (iii) measured lipid R1 values are positively correlated with absolute pO2 values in both tumor models (P = 0.0275, r = 0.3726); and (iv) changes in the R1 of lipids are more sensitive than changes in the global R1. As this technique presents unique translational properties, it seems promising for the individual longitudinal monitoring of tumor oxygenation in a clinical setting.

Conductivity of Gd-doped BaCeO3 protonic conductor in Н2–Н2О–О2 atmospheres

In the present investigation, a radically new and simple method of evaluation of the proton conductivity is proposed. This method is based on the conductivity measurement of ceramic materials depending on the oxygen partial pressure (pO2) at a gradual transition from the atmosphere of pure oxygen to one of wet hydrogen: O2 → O2 (H2O) → H2O (O2) → H2O → H2O (H2) → H2 (H2O).Experimental data of total conductivities for the solid electrolyte BaCe0.9Gd0.1O3–δ (BCG) have been fitted with modeling ones in accordance with the defect chemistry model at 600, 750 and 900 °C. Experimental and theoretical relationships correlate well with each other, demonstrating the success of the proposed model description.Analysis of dependences of the total conductivity as a function of pO2 with simultaneous change of pO2 and water partial pressure (pH2O) allows the estimation of the contribution of the partial conductivities (protonic, oxygen ionic, electronic) in the total one and the identification of the areas of purely ionic and purely protonic conductivity. Using the obtained data, some transport phenomena of proton-conducting materials, which were not previously interpreted, are discussed.

Age-related metabolic fatigue during low glucose conditions in rat hippocampus

Previous reports have indicated that with aging, intrinsic brain tissue changes in cellular bioenergetics may hamper the brain's ability to cope with metabolic stress. Therefore, we analyzed the effects of age on neuronal sensitivity to glucose deprivation by monitoring changes in field excitatory postsynaptic potentials (fEPSPs), tissue Po2, and NADH fluorescence imaging in the CA1 region of hippocampal slices obtained from F344 rats (1–2, 3–6, 12–20, and >22 months). Forty minutes of moderate low glucose (2.5 mM) led to approximately 80% decrease of fEPSP amplitudes and NADH decline in all 4 ages that reversed after reintroduction of 10 mM glucose. However, tissue slices from 12 to 20 months and >22-month-old rats were more vulnerable to low glucose: fEPSPs decreased by 50% on average 8 minutes faster compared with younger slices. Tissue oxygen utilization increased after onset of 2.5 mM glucose in all ages of tissue slices, which persisted for 40 minutes in younger tissue slices. But, in older tissue slices the increased oxygen utilization slowly faded and tissue Po2 levels increased toward baseline values after approximately 25 minutes of glucose deprivation. In addition, with age the ability to regenerate NADH after oxidation was diminished. The NAD+/NADH ratio remained relatively oxidized after low glucose, even during recovery. In young slices, glycogen levels were stable throughout the exposure to low glucose. In contrast, with aging utilization of glycogen stores was increased during low glucose, particularly in hippocampal slices from >22 months old rats, indicating both inefficient metabolism and increased demand for glucose. Lactate addition (20 mM) improved oxidative metabolism by directly supplementing the mitochondrial NADH pool and maintained fEPSPs in young as well as aged tissue slices, indicating that inefficient metabolism in the aging tissue can be improved by directly enhancing NADH regeneration.