Oxygen delivery from the cerebral microvasculature to tissue is governed by a single time constant of approximately 6 seconds

Payne, Stephen J.; Lucas, Claire Huang

doi:10.1111/micc.12428

Cited by 18 publications

(22 citation statements)

References 32 publications

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“…Generally, these efforts fall into two types. One type adopts a reductionist approach using simplified networks to highlight global blood flow distribution patterns [7,24–28]. The second type follows a bottom-up strategy which aims at replicating relevant microcirculatory components down to the level of the cellular ensemble.…”

Section: Introductionmentioning

confidence: 99%

“…Noteworthy examples include quantifying the neurovascular coupling in functional hyperemia [3], analysis of pressure drop dependence on cortical depth [22], predictions of blood flow control by intra-cortical arterioles [9], and cortical oxygen distribution [29,30]. The ultimate goal of bottom-up models is a hemodynamic simulation of the entire brain , yet virtual circulation models of the whole brain have been perceived as intractable due to size and nonlinearity of the mathematical coupling between blood flow and oxygen kinetics [24].…”

Section: Introductionmentioning

confidence: 99%

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Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

et al. 2018

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Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

et al. 2018

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“…Furthermore, the model shows that

P_{normalT O_{2}}

is well controlled in anaemia with little error signal to drive CBF compared to arterial hypoxia, meaning that the regulator gain must be extremely high for anaemia, which again is a scenario of low probability. Furthermore, the time constant for oxygen delivery from the cerebral microvasculature to tissue is in the order of 6 s (Payne & Lucas, ), which is too long to explain the control of CBF. These differences suggest separate CBF regulatory mechanisms for anaemia and hypoxia.…”

Section: Discussionmentioning

confidence: 99%

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Duffin

Hare

Fisher

2020

The Journal of Physiology

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Key points The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. Abstract A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

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“…The governing equations of these models are summarised in Appendix B. All of the model parameters remained the same as previously used 27 , except for the maximum CMRO 2 , which was set as 6.72×10- 4 cm 3 /(cm 3 · s) based on human data 36 and the haematocrit was assumed to be a constant value of 0.45 which has been used previously to simulate the blood flow 15 .…”

Section: Methodsmentioning

confidence: 99%

Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death

Xue

El-Bouri

Józsa

et al. 2021

Preprint

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Thrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is due to the clot fragments that block the downstream vessels. In this paper, we present a new way of quantifying the effects of cerebral microthrombi on oxygen transport to tissue in terms of hypoxia and ischaemia. The oxygen transport was simulated with the Green’s function method on physiologically accurate microvascular cubes, which was found independent of both microvascular geometry and length scale. The microthrombi occlusions were then simulated in the microvasculature, which were extravasated over time with a new vessel extravasation model. The tissue hypoxic fraction was fitted as a sigmoidal function of vessel blockage fraction, which was then taken to be a function of time after the formation of microthrombi occlusions. A novel hypoxia-based 3-state cell death model was finally proposed to simulate the hypoxic tissue damage over time. Using the cell death model, the impact of a certain degree of microthrombi occlusions on tissue viability and microinfarct volume can be predicted over time. Quantifying the impact of microthrombi on oxygen transport and tissue death will play an important role in full brain models of ischaemic stroke and thrombectomy.

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Oxygen delivery from the cerebral microvasculature to tissue is governed by a single time constant of approximately 6 seconds

Abstract: The overall response time for the whole network is approximately 6 seconds; this value indicates that the flow response to increases in metabolic activity cannot be driven solely by changes in tissue oxygenation.

Cited by 18 publications

References 32 publications

Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death

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