scholarly journals The Roles of Cerebral Blood Flow, Capillary Transit Time Heterogeneity, and Oxygen Tension in Brain Oxygenation and Metabolism

2011 ◽  
Vol 32 (2) ◽  
pp. 264-277 ◽  
Author(s):  
Sune N Jespersen ◽  
Leif Østergaard

Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow ( CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction ( OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic—metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia—reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism.

2015 ◽  
Vol 35 (5) ◽  
pp. 806-817 ◽  
Author(s):  
Hugo Angleys ◽  
Leif Østergaard ◽  
Sune N Jespersen

We recently extended the classic flow–diffusion equation, which relates blood flow to tissue oxygenation, to take capillary transit time heterogeneity ( CTH) into account. Realizing that cerebral oxygen availability depends on both cerebral blood flow ( CBF) and capillary flow patterns, we have speculated that CTH may be actively regulated and that changes in the capillary morphology and function, as well as in blood rheology, may be involved in the pathogenesis of conditions such as dementia and ischemia-reperfusion injury. The first extended flow–diffusion equation involved simplifying assumptions which may not hold in tissue. Here, we explicitly incorporate the effects of oxygen metabolism on tissue oxygen tension and extraction efficacy, and assess the extent to which the type of capillary transit time distribution affects the overall effects of CTH on flow–metabolism coupling reported earlier. After incorporating tissue oxygen metabolism, our model predicts changes in oxygen consumption and tissue oxygen tension during functional activation in accordance with literature reports. We find that, for large CTH values, a blood flow increase fails to cause significant improvements in oxygen delivery, and can even decrease it; a condition of malignant CTH. These results are found to be largely insensitive to the choice of the transit time distribution.


2021 ◽  
Author(s):  
Klaus U. Koch ◽  
Irene K. Mikkelsen ◽  
Ulrick S. Espelund ◽  
Hugo Angleys ◽  
Anna Tietze ◽  
...  

Background This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. Methods In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. Results Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], −0.6 [−0.9 to −0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], −0.4[−0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. Conclusions Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


2010 ◽  
Vol 112 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Mads Rasmussen ◽  
Niels Juul ◽  
Søren M. Christensen ◽  
Kristjana Y. Jónsdóttir ◽  
Carsten Gyldensted ◽  
...  

Background The regional cerebral blood flow (CBF) response to propofol and indomethacin may be abnormal in patients with brain tumors. First, the authors tested the hypothesis that during propofol anesthesia alone and combined with indomethacin, changes in CBF, cerebral blood volume (CBV), and plasma mean transit time (MTT) differ in the peritumoral tissue compared with the contralateral normal brain region. Second, the authors tested the hypothesis that CBF and CBV are reduced and MTT is prolonged, in both regions during propofol anesthesia and indomethacin administration compared with propofol alone. Methods The authors studied eight patients subjected to craniotomy under propofol-fentanyl anesthesia for supratentorial brain tumors. Magnetic resonance imaging, including perfusion- and diffusion-weighted and structural sequences, was performed (1) on the day before surgery, (2) before and (3) after administration of indomethacin in the propofol-fentanyl anesthetized patient, and (4) 2 days after surgery. Maps of CBF, CBV, and MTT were calculated. The regions of interest were peritumoral gray matter and opposite contralateral gray matter. Analysis of variance was used to analyze flow data. Results Propofol anesthesia was associated with a median 32% (range, 3-61%) and 47% (range, 17-67%) reduction in CBF in the peritumoral and contralateral regions, respectively.The interaction between intervention with propofol and indomethacin and region of interest was not significant for any flow modalities. Neither intervention nor region was significant for MTT, CBF, and CBV (P > 0.05). Conclusion The CBF, CBV, and MTT responses to propofol and indomethacin are not different in the peritumoral region compared with contralateral brain tissue. Indomethacin did not further influence regional CBF, CBV, and MTT during propofol anesthesia.


Neurosurgery ◽  
2001 ◽  
Vol 48 (2) ◽  
pp. 436-440 ◽  
Author(s):  
Colin P. Derdeyn ◽  
DeWitte T. Cross ◽  
Christopher J. Moran ◽  
Ralph G. Dacey

Abstract OBJECTIVE AND IMPORTANCE The presence of reduced blood flow and increased oxygen extraction fraction (OEF) (misery perfusion) in the hemisphere distal to an occluded carotid artery is a proven risk factor for subsequent stroke. Whether angioplasty of intracranial stenosis is sufficient to reverse this condition has not been documented. CLINICAL PRESENTATION A 67-year-old man exhibited progressive right hemispheric ischemic symptoms despite maximal antiplatelet and antithrombotic therapy. Angiography demonstrated focal 80% stenosis of the supraclinoid segment of the ipsilateral internal carotid artery. TECHNIQUE 15O positron emission tomographic measurements of cerebral blood flow and OEF were made before and after transfemoral percutaneous angioplasty. OEF values measured before angioplasty were elevated in the middle cerebral artery distal to the stenosis. Angioplasty reduced the degree of luminal stenosis to 40% (linear diameter). OEF values measured 36 hours after angioplasty were normal. CONCLUSION Angioplasty of intracranial stenosis can restore normal cerebral blood flow and oxygen extraction, despite mild residual stenosis after the procedure. Hemodynamic measurements may be useful for the identification of patients with the greatest potential to benefit from angioplasty.


Radiology ◽  
1999 ◽  
Vol 210 (2) ◽  
pp. 519-527 ◽  
Author(s):  
A. Gregory Sorensen ◽  
William A. Copen ◽  
Leif Østergaard ◽  
Ferdinando S. Buonanno ◽  
R. Gilberto Gonzalez ◽  
...  

2006 ◽  
Vol 100 (3) ◽  
pp. 850-857 ◽  
Author(s):  
Kenneth M. Tichauer ◽  
Derek W. Brown ◽  
Jennifer Hadway ◽  
Ting-Yim Lee ◽  
Keith St. Lawrence

Impaired oxidative metabolism following hypoxia-ischemia (HI) is believed to be an early indicator of delayed brain injury. The cerebral metabolic rate of oxygen (CMRO2) can be measured by combining near-infrared spectroscopy (NIRS) measurements of cerebral blood flow (CBF) and cerebral deoxy-hemoglobin concentration. The ability of NIRS to measure changes in CMRO2 following HI was investigated in newborn piglets. Nine piglets were subjected to 30 min of HI by occluding both carotid arteries and reducing the fraction of inspired oxygen to 8%. An additional nine piglets served as sham-operated controls. Measurements of CBF, oxygen extraction fraction (OEF), and CMRO2 were obtained at baseline and at 6 h after the HI insult. Of the three parameters, only CMRO2 showed a persistent and significant change after HI. Five minutes after reoxygenation, there was a 28 ± 12% (mean ± SE) decrease in CMRO2, a 72 ± 50% increase in CBF, and a 56 ± 19% decrease in OEF compared with baseline ( P < 0.05). By 30 min postinsult and for the remainder of the study, there were no significant differences in CBF and OEF between control and insult groups, whereas CMRO2 remained depressed throughout the 6-h postinsult period. This study demonstrates that NIRS can measure decreases in CMRO2 caused by HI. The results highlight the potential for NIRS to be used in the neonatal intensive care unit to detect delayed brain damage.


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