Tracer Oxygen Distribution Is Barrier-Limited in the Cerebral Microcirculation

Kassissia, Ibrahim; Goresky, Carl A.; Rose, Colin P.; Schwab, Andreas; Simard, André; Huet, Pierre‐Michel; Bach, Glen G.

doi:10.1161/01.res.77.6.1201

Cited by 57 publications

(40 citation statements)

References 39 publications

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“…The baseline blood flow in the somatosensory cortex was measured by our group to be 150 ml/min/100g under similar experimental conditions . The surface area and the permeability values were adopted from the literature (Liu, et al, 1994;Kassissia, et al, 1995). There are several reports for these values in the literature and the values selected are close to their respective average values.…”

Section: Discussionmentioning

confidence: 99%

“…When using suppressed CBF condition data, this baseline blood flow level was adjusted by the relative change in LDF signal between control and suppressed CBF conditions. Lastly, the permeability-surface area (PS c ) parameter value was obtained from the literature and assumed to represent the control condition permeability-surface area (Kassissia, et al, 1995). Under suppressed CBF conditions, the permeability-surface area product was increased to 7900 ml/min/100g (from 7000 ml/min/ 100g) to match the baseline metabolic rate of the control condition.…”

Section: Oxygen Exchange Modelmentioning

confidence: 99%

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Dynamics of oxygen delivery and consumption during evoked neural stimulation using a compartment model and CBF and tissue PO2 measurements

Vazquez

Masamoto²,

Kim

2008

NeuroImage

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The dynamics of blood oxygen delivery and tissue consumption produced by evoked stimulation of the rat somato-sensory cortex were investigated. Tissue oxygen tension (P O2 ) and laser Doppler flowmetry (LDF) measurements were recorded under two experimental conditions: normal, which represented both oxygen delivery and consumption, and suppressed CBF (achieved using a vasodilator), which only represented tissue oxygen consumption. Forepaw stimulation for 10 s produced increases of 27.7% and 48.8% in tissue P O2 and LDF signal under normal conditions, respectively. The tissue P O2 response peaked 9.8 s after stimulation onset and did not show any early transient decreases indicating that measurable oxygen deficits are not required to increase the delivery of oxygen by blood flow. Under suppressed CBF conditions, the LDF signal was mostly suppressed while the tissue P O2 decreased by 11.7% and reached a minimum 10.8 s after stimulation onset. These data were analyzed using a dynamic model that described the transport of oxygen from blood to tissue. In order to explain the differences between the model prediction of the tissue P O2 changes and the experimental data, several hypothetical scenarios were considered, such as changes in the vascular volume, permeability-surface area or arterial oxygenation. The increase in tissue P O2 was found to probably require the recruitment of upstream oxygen from larger arteries as well as increases in the vascular volume at the oxygen exchange sites. The amplitude of the estimated tissue tension of oxygen delivered was about 2.7× larger than the estimated consumption under normal conditions (45.7% vs. 17.1%, respectively).

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Section: Discussionmentioning

confidence: 99%

Section: Oxygen Exchange Modelmentioning

confidence: 99%

Dynamics of oxygen delivery and consumption during evoked neural stimulation using a compartment model and CBF and tissue PO2 measurements

Vazquez

Masamoto²,

Kim

2008

NeuroImage

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“…The recent models assume that the human brain has unidirectional flux of oxygen out of the capillary. This assumption appears justified by the finding that there is minimal oxygen in brain tissue compared with blood, using transit time measures (42). However, because of the very high oxygen content of blood (from hemoglobin), the actual level of human brain oxygen is difficult to estimate with these techniques.…”

Section: Discussionmentioning

confidence: 99%

Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data

Mintun

Lundstrom

Snyder

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

330

246

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Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO2 during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [ 15 O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen. It was long assumed that changes in cerebral blood flow (CBF) and in the cerebral metabolic rate of oxygen (CMRO 2 ) are tightly coupled in both resting and active brain states. This assumption resulted from the premises that the brain needs oxygen, that CBF is a main homeostatic factor for oxygen supply regulation, and that oxygen availability should be adjusted to meet tissue needs (1). It is known that the brain needs an abundant supply of oxygen and that, at rest, 80-92% of its ATP comes from oxidative metabolism of glucose. Early studies by Kety and Schmidt (2) and Cohen et al. (3) demonstrated that resting CBF does change with hypoxia and hyperoxia, thereby suggesting that CBF regulates oxygen delivery, although it was noted that blood oxygen levels but not tissue oxygen levels likely triggered these CBF changes (1). Therefore, if the cerebral oxygen supply was closely regulated to match tissue demands, then functional activation, which implies the need for additional ATP and oxygen, should cause a coupled increase in both CBF and CMRO 2 . However, two positron emission tomography (PET) studies conducted by Fox et al. (4,5) revealed that in humans large, stimulus-induced increases in CBF (Ϸ30% and 50%) were accompanied by only small increases in CMRO 2 (Ϸ5%). Others using PET and functional MRI confirmed these findings (6-10). The data indicated that, during short-term functional activation, CBF and CMRO 2 are not directly coupled.Recently, several reports using theoretical models suggested that the apparent uncoupling of CMRO 2 and CBF might actually be a tight nonlinear coupling. Mathematical models of oxygen delivery to the brai...

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“…We previously formulated a mechanism of nonlinear flowmetabolism coupling in normothermia (16,20,60) based on the observation of diffusion-limited transport of oxygen to brain tissue (21,34), and we validated the formulation for the cases of visual cortex activation (20), cortical motor activation (19), and arterial hypoxemia (17). The mechanism dictates the rate of blood flow needed to supply the tissue with an adequate amount of oxygen…”

Section: Nonlinear Flow-metabolism Couplingmentioning

confidence: 99%

Neuroprotection in hypothermia linked to redistribution of oxygen in brain

Sakoh

Gjedde²

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Hypothermia improves the outcome of acute ischemic stroke, traumatic injury, and inflammation of brain tissue. We tested the hypothesis that hypothermia reduces the energy metabolism of brain tissue to a level that is commensurate with the prevailing blood flow and hence allows adequate distribution of oxygen to the entire tissue. To determine the effect of 32 degrees C hypothermia on brain tissue, we measured the sequential changes of physiological variables by means of PET in pigs. Cerebral blood flow and oxygen consumption (cerebral metabolic rate of oxygen) declined to 50% of the baseline in 3 and 5 h, respectively, thus elevating the oxygen extraction fraction to 140% of the baseline at 3 h. The results are consistent with the claim that cooling of the brain to 32 degrees C couples both energy metabolism and blood flow to a lower rate of work of the entire tissue.

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Tracer Oxygen Distribution Is Barrier-Limited in the Cerebral Microcirculation

Cited by 57 publications

References 39 publications

Dynamics of oxygen delivery and consumption during evoked neural stimulation using a compartment model and CBF and tissue PO2 measurements

Dynamics of oxygen delivery and consumption during evoked neural stimulation using a compartment model and CBF and tissue PO2 measurements

Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data

Neuroprotection in hypothermia linked to redistribution of oxygen in brain

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