Local Oxygen Demand Research Articles

Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees.

The microvasculature plays a key role in oxygen transport in the mammalian brain. Despite the close coupling between cerebral vascular geometry and local oxygen demand, recent experiments have reported that microvascular occlusions can lead to unexpected distant tissue hypoxia and infarction. To better understand the spatial correlation between the hypoxic regions and the occlusion sites, we used both in vivo experiments and in silico simulations to investigate the effects of occlusions in cerebral penetrating arteriole trees on tissue hypoxia. In a rat model of microembolisation, 25 μm microspheres were injected through the carotid artery to occlude penetrating arterioles. In representative models of human cortical columns, the penetrating arterioles were occluded by simulating the transport of microspheres of the same size and the oxygen transport was simulated using a Green's function method. The locations of microspheres and hypoxic regions were segmented, and two novel distance analyses were implemented to study their spatial correlation. The distant hypoxic regions were found to be present in both experiments and simulations, and mainly due to the hypoperfusion in the region downstream of the occlusion site. Furthermore, a reasonable agreement for the spatial correlation between hypoxic regions and occlusion sites is shown between experiments and simulations, which indicates the good applicability of in silico models in understanding the response of cerebral blood flow and oxygen transport to microemboli.

Effect of Natural Ilmenite on the Solid Biomass Conversion of Inhomogeneous Fuels in Small-Scale Bubbling Fluidized Beds

The application of oxygen carriers as alternative bed material in fluidized bed combustion originates from chemical lopping processes. They serve as oxygen transport agents undergoing consecutive redox cycles. Thereby, oxygen carriers can provide surplus oxygen in oxygen-lean areas of fluidized bed combustion processes. In turn, re-oxidation takes place in oxygen-rich reactor parts. A more homogeneous combustion and reduced CO emissions follow during steady-state operation. However, especially regarding solid biomass conversion, inhomogeneous fuel qualities result in transient combustion conditions. Therefore, this research deals with the influence of the oxygen carrier ilmenite on solid biomass conversion. Separated batch experiments with methane (volatile), char and wood pellets took place in a laboratory bubbling fluidized bed reactor. They reveal that ilmenite enhances the in-bed CO2 yield by up to 63% during methane combustion. Batch char experiments confirm that solid–solid reactions with ilmenite are negligible. However, heterogeneous gas–solid reactions reduce the O2 partial pressure and limit the char conversion rate. The batch wood pellet experiments show that the ilmenite oxygen buffering effect is mitigated due to high local oxygen demand around the pellets and limited pellet distribution in the bed. Finally, the continuous operation in a 100 kWth BFB with inhomogeneous fuel input indicates a higher in-bed fuel conversion and confirms lower CO emissions and less fluctuation in the flue gas during inhomogeneous fuel supply.

The Microvascular Lattice: An Updated Paradigm of Flow Distribution Through Capillary Networks

BackgroundCapillaries, as the smallest vessels in the microcirculation, represent the most essential site for oxygen delivery; yet, given their overwhelming density and complicated geometry, understanding how they integrate within the broader microvascular network has been challenging.Classical microvascular flow modelling has used linear branching networks such that each capillary bundle (CB) corresponds to a unique arteriolar‐venular pair with one‐directional pathway of flow. However, it has long been observed in vivo that terminal arterioles supply multiple CBs and similarly, post‐capillary venules collect from multiple CBs. Such a network forms a lattice‐like structure with an alternating pattern of arterioles, CBs, and venules.ObjectiveWe aim to develop a mathematical model for the microvascular lattice that can be applied to study blood flow properties through capillary networks in skeletal muscle.Methods/ResultsMicrovascular lattice networks are generated from our own rodent intravital videomicroscopy data and compared to data reported in the literature. Distinct CBs are selected and their anatomical features are delineated with 3‐D reconstruction software. Capillary hemodynamics (RBC velocity, RBC supply rate, hematocrit) are extracted from video data and used to characterize the flow within and between multiple CBs. The generalized architecture of a microvascular lattice is then extrapolated from our experimental data and applied to a dual‐phase steady‐state blood flow model. Flow properties of the lattice are compared to those of a classical linear branching network ‐ both containing the same number of CBs.Conclusions/ImpactThe microvascular lattice represents an updated paradigm for describing blood flow through capillary networks. This lattice structure raises important questions regarding how flow can be regulated to support local oxygen demand and how larger microvessels interact with capillaries within the microcirculation. Furthermore, CB functional data for a variety of microvascular conditions can be inputted into this lattice model to determine how alterations to capillary architecture affect overall flow through the microvascular network.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Temporal fractal analysis of the rs-BOLD signal identifies brain abnormalities in autism spectrum disorder.

BackgroundBrain connectivity in autism spectrum disorders (ASD) has proven difficult to characterize due to the heterogeneous nature of the spectrum. Connectivity in the brain occurs in a complex, multilevel and multi-temporal manner, driving the fluctuations observed in local oxygen demand. These fluctuations can be characterized as fractals, as they auto-correlate at different time scales. In this study, we propose a model-free complexity analysis based on the fractal dimension of the rs-BOLD signal, acquired with magnetic resonance imaging. The fractal dimension can be interpreted as measure of signal complexity and connectivity. Previous studies have suggested that reduction in signal complexity can be associated with disease. Therefore, we hypothesized that a detectable difference in rs-BOLD signal complexity could be observed between ASD patients and Controls.Methods and findingsAnatomical and functional data from fifty-five subjects with ASD (12.7 ± 2.4 y/o) and 55 age-matched (14.1 ± 3.1 y/o) healthy controls were accessed through the NITRC database and the ABIDE project. Subjects were scanned using a 3T GE Signa MRI and a 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 30/2000ms) where 300 time points were acquired. Motion correction was performed on the functional data and anatomical and functional images were aligned and spatially warped to the N27 standard brain atlas. Fractal analysis, performed on a grey matter mask, was done by estimating the Hurst exponent in the frequency domain using a power spectral density approach and refining the estimation in the time domain with de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group and in the ASD group to create ROI-based Z-scores for the ASD patients. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels were eliminated from subsequent analysis. To maintain a 95% confidence level, only regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were included in the analysis. We found that the main regions, where signal complexity significantly decreased among ASD patients, were the amygdala (p = 0.001), the vermis (p = 0.02), the basal ganglia (p = 0.01) and the hippocampus (p = 0.02). No regions reported significant increase in signal complexity in this study. Our findings were correlated with ADIR and ADOS assessment tools, reporting the highest correlation with the ADOS metrics.ConclusionsBrain connectivity is best modeled as a complex system. Therefore, a measure of complexity as the fractal dimension of fluctuations in brain oxygen demand and utilization could provide important information about connectivity issues in ASD. Moreover, this technique can be used in the characterization of a single subject, with respect to controls, without the need for group analysis. Our novel approach provides an ideal avenue for personalized diagnostics, thus providing unique patient specific assessment that could help in individualizing treatments.

Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD.

Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations. To counter the hypoxic challenge and ensure their survival, mucosal cells induce adaptive responses, including the activation of hypoxia-inducible factors (HIFs) and modulation of nuclear factor-κB (NF-κB). Both pathways are tightly regulated by oxygen-sensitive prolyl hydroxylases (PHDs), which therefore represent promising therapeutic targets for IBD. In this Review, we discuss the involvement of mucosal hypoxia and hypoxia-induced signalling in the pathogenesis of IBD and elaborate in detail on the role of HIFs, NF-κB and PHDs in different cell types during intestinal inflammation. We also provide an update on the development of PHD inhibitors and discuss their therapeutic potential in IBD.

Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for metabolic flow regulation in heterogeneous microvascular networks

The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.

Biceps brachii muscle oxygenation in electrical muscle stimulation

The purpose of this study was to compare between electrical muscle stimulation (EMS) and maximal voluntary (VOL) isometric contractions of the elbow flexors for changes in biceps brachii muscle oxygenation (tissue oxygenation index, TOI) and haemodynamics (total haemoglobin volume, tHb = oxygenated-Hb + deoxygenated-Hb) determined by near-infrared spectroscopy (NIRS). The biceps brachii muscle of 10 healthy men (23-39 years) was electrically stimulated at high frequency (75 Hz) via surface electrodes to evoke 50 intermittent (4-s contraction, 15-s relaxation) isometric contractions at maximum tolerated current level (EMS session). The contralateral arm performed 50 intermittent (4-s contraction, 15-s relaxation) maximal voluntary isometric contractions (VOL session) in a counterbalanced order separated by 2-3 weeks. Results indicated that although the torque produced during EMS was approximately 50% of VOL (P<0.05), there was no significant difference in the changes in TOI amplitude or TOI slope between EMS and VOL over the 50 contractions. However, the TOI amplitude divided by peak torque was approximately 50% lower for EMS than VOL (P<0.05), which indicates EMS was less efficient than VOL. This seems likely because of the difference in the muscles involved in the force production between conditions. Mean decrease in tHb amplitude during the contraction phases was significantly (P<0.05) greater for EMS than VOL from the 10th contraction onwards, suggesting that the muscle blood volume was lower in EMS than VOL. It is concluded that local oxygen demand of the biceps brachii sampled by NIRS is similar between VOL and EMS.

Causes for spatial heterogeneity of perfusion and function

In many tissues, including the heart, perfusion and metabolic activity are heterogeneous and spatially correlated. To investigate the underlying mechanisms and cause/effect relations, a mathematical simulation model based on experimental data for microvascular networks was used. Results show that unavoidable geometric heterogeneities of vascular networks cause heterogeneity of blood flow and oxygen levels which cannot be eliminated by increasing metabolic sensitivity of diameter adaptation. Additional adaptation of oxygen demand to local oxygen availability allows increased oxygen extraction and functional capacity. It also establishes a correlation between local oxygen demand and flow rate, as observed experimentally. These findings suggest that stochastic processes of angiogenesis and not pre‐existing heterogeneities of local metabolic demand underlie the observed spatial heterogeneity of perfusion and function.

Origins of heterogeneity in tissue perfusion and metabolism

In the heart and other tissues, perfusion and metabolic activity are heterogeneous and spatially correlated. The goal of this work is to investigate the causes of this behaviour. Theoretical simulations are used to examine the effects on flow distribution and oxygen levels in terminal vascular beds of inherent irregularity in network structure, considering structural adaptation of vessel diameters to haemodynamic and metabolic stimuli, and adaptation of oxygen demand to local oxygen availability. A mathematical model based on experimentally observed microvascular network structures (rat mesentery and m. sartorius) is used to simulate blood flow, oxygen transport, and adaptation of vessel diameters and tissue oxygen demand. Inherent geometric heterogeneities of vascular networks cause heterogeneity of blood flow and oxygen levels that cannot be eliminated by increasing metabolic sensitivity of diameter adaptation. Adaptation of oxygen demand to differences in oxygen availability causes increased oxygen extraction, implying improved functional capacity, and establishes a correlation between local oxygen demand and flow rate, as observed experimentally. Such a correlation is not predicted if the heterogeneity of oxygen demand is assumed to be an intrinsic tissue property. A central mechanism generating heterogeneous perfusion is the inevitable structural heterogeneity of terminal vascular beds, which cannot be fully compensated by structural adaptation of vessel diameters. Heterogeneity of metabolism may result from adaptation of tissue function to the heterogeneous oxygen availability. These findings are of interest for the understanding of tissue function, including the heart, and of results obtained by corresponding imaging approaches.

Investigation of hydrogeologic processes in a dipping layer structure: 2. Transport and biodegradation of organics

Numerical simulation tools have been used to study the dominating processes during transport of aromatic hydrocarbons in the unsaturated soil zone. Simulations were based on field observations at an experimental site located on a glacial delta plain with pronounced layered sedimentary structures. A numerical model for transport in the unsaturated zone, SWMS-3D, has been extended to incorporate coupled multispecies transport, microbial degradation following Monod kinetics and gas diffusive transport of oxygen and hydrocarbons. The flow field parameters were derived from previous work using nonreactive tracers. Breakthrough curves (BTC) from the hydrocarbon field experiment were used to determine sorption parameters and Monod kinetic parameters using a fitting procedure. The numerical simulations revealed that the assumption of homogeneous layers resulted in deviations from the field observations. The deviations were more pronounced with incorporation of reactive transport, compared with earlier work on nonreactive transport. To be able to model reasonable BTC, sorption had to be reduced compared to laboratory experiments. The initial biomass and the maximum utilisation rate could be adjusted to capture both the initial lag phase and the overall degradation rate. Nevertheless, local oxygen limitation is predicted by the model, which was not observed in the field experiment. Incorporation of evaporation and diffusive gas transport of the hydrocarbons did not significantly change the local oxygen demand. The main cause of the observed discrepancies between model and field are attributed to channelling as a result of small-scale heterogeneities such as biopores.

On the timing characteristics of the apparent diffusion coefficient contrast in fMRI.

For the past 10 years, functional MRI (fMRI) has seen rapid progress in both clinical and basic science research. Most of the imaging techniques are based on the blood oxygenation level-dependent (BOLD) contrast which arises from the field perturbation of the paramagnetic deoxyhemoglobin due to the mismatch between the local oxygen demand and delivery. Because the changes of oxygenation level take place mostly in the veins, the dominant signal sources of the BOLD signal are intra- and extravascular proton pools of the veins. Perfusion imaging methods, developed parallel to the BOLD technique, seek to quantify the blood flow and perfusion. Recently, perfusion imaging using arterial spin tagging methods have been used to study brain function by investigating the changes of the blood flow and perfusion during brain activation, thereby generating an alternative contrast mechanism to the functional brain imaging. Since most of these methods require tagging pulse and wait time for blood to be delivered to the imaged slice, the temporal resolution may not be optimal. Dynamic intravoxel incoherent motion (IVIM) weighting schemes using apparent diffusion coefficient (ADC) contrast were suggested to image the relative changes of the in-plane blood flow during brain function. In this report, it was demonstrated that, in addition to the spatial discrepancies of the activated areas, the time course based on the ADC contrast consistently precedes that from the BOLD contrast with timing offset on the order of 1 sec. Since arterial networks would have different spatial locations and preceding temporal characters, the findings in this report are indicative that the ADC contrast is sensitive to the arterial blood flow changes.

Computational modelling of pulverised fuel burnout in tangentially fired furnaces

Two operating furnaces are completely modelled computationally to investigate incomplete fuel burnout. Combustion parameters for a range of coals are obtained from laboratory data. The burnout predictions for seven operating conditions are found to agree very well with the test data. Unburned carbon in the ash hopper is also predicted accurately. This study validates the computational model carbon burnout predictions and shows that laboratory derived coal combustion data can be used to predict full-scale furnace performance. Carbon burnout is found to be quite sensitive to the flow distribution between burners. A cause for incomplete carbon burnout is found to be low local oxygen concentrations for some of the conditions in these tangentially fired furnaces. Particle trajectories concentrate near the furnace walls because of the cyclonic action of the swirling flow causing high local oxygen demand.

Responses to oxygen deprivation: variations among human corneas

The cornea's interface with the atmosphere makes it uniquely accessible among avascular tissue for the study of local oxygen demand and proximal reservoir dynamics. Corneal oxygen-uptake rates obtained under normoxic vs hypoxic conditions are not predictive of each other. Proximal tissue reservoirs appear to play a role in moderating oxygen demands following periods of hypoxic stress: as the ratio of epithelia/stromal thickness rises, so does oxygen demand (r = +0.932, P = 0.01). The thickness of the stroma was most closely related to the oxygen uptake rates associated with the normal, open eye (r = +0.773, P = 0.07), whereas the thickness of the epithelium was more closely related to rates obtained after the cornea had been deprived of oxygen (r = +0.783, P = 0.07).

Muscle PO2 in the initial phase of increased local oxygen demand (rhythmical muscle contraction) in rats with portacaval shunt (PCA).

The influence of a hyperdynamic syndrome caused by PCA on PO2 distribution in skeletal muscle of rats during the initial phase of muscle activity was examined. Rhythmical muscle contraction of the m. biceps femoris was induced by direct electrical stimulation. Tissue PO2 of the contracting muscle was recorded continuously from the start of the 210 s-long activity period up to 140 s after the last contraction using a multiwire surface electrode. In comparison with controls no different behaviour of mean muscle PO2 in the initial phase of contraction was found. After muscle activity mean PO2 decreased to a lower level in rats with PCA than in controls. This might be a further indication of the disturbing influence of a hyperdynamic syndrome on the regulating mechanisms of the microcirculation.

Left ventricular mechanics related to the local distribution of oxygen demand throughout the wall.

The complex interactions between left ventricular mechanics and the oxygen demand is studied by relating the left ventricular transmural oxygen demand to the myocardial structural and dynamic characteristics. The study utilizes a recent model of left ventricular contraction, which is based on a nested shell spheroidal geometry, a fan-like fibrous structure, the twisting motion of the left ventricle over its long axis, a transmural electrical activation propagation and the basic laws of sarcomere dynamics. The local "axial" stress (in the direction of the fibers) and the instantaneous sarcomere length are used to calculate the spatial distribution of the intramural oxygen demand per beat Vo2(y), where y is the distance from the endocardium. The normalized local sarcomere stress-length area SLAn(y) is related linearly to Vo2(y) by: Vo2(y) = K1 X SLAn(y) + K2, where K1 and K2 are constants. The calculations show a transmural metabolic gradient which is characterized by higher values of Vo2(y) in the endocardial layers than in the epicardial layers. Shorter endocardial sarcomeres and the twisting motion of the left ventricle around the long axis decrease the metabolic gradient across the wall, while a slow transmural electrical propagation wave as well as a wider angle of distribution of the fan-like fiber architecture increases the transmural metabolic gradient. Integration of the local oxygen demand across the left ventricular wall yields global values in agreement with those based on Suga's pressure-volume area approach. The model thus provides a qualitative and quantitative tool to assess the relation of the local and global oxygen demand to the complex left ventricular structure, fiber mechanics, and the dynamics of contraction.

Retinal Vascular Changes in Retrograde Optic Atrophy

Five patients with unilateral optic atrophy of extraocular origin had a normal retinal vasculature. Clinical examination of the patients included color fundus photographs and fluorescein angiography. After comparing the blood vessels in the blind eye with those in the normal fellow eye, we concluded that vascular attenuation is neither invariably associated with optic atrophy, nor solely caused by decreased local oxygen demand in the retina.