scholarly journals Progressive Derangement of Periinfarct Viable Tissue in Ischemic Stroke

1992 ◽  
Vol 12 (2) ◽  
pp. 193-203 ◽  
Author(s):  
W.-D. Heiss ◽  
M. Huber ◽  
G. R. Fink ◽  
K. Herholz ◽  
U. Pietrzyk ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Metabolic Rate ◽  
Effective Treatment ◽  
Brain Slices ◽  
Border Zone ◽  
Oxygen Extraction Fraction ◽  
Metabolic Derangement ◽  
Cerebral Metabolic Rate ◽  
Observation Period

Sixteen patients were studied by multitracer positron emission tomography (PET) within 6–48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13–25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 ± 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 ± 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke.

scholarly journals Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e018560 ◽  
Author(s):  
Klaus Ulrik Koch ◽  
Anna Tietze ◽  
Joel Aanerud ◽  
Gorm von Öettingen ◽  
Niels Juul ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Metabolic Rate ◽  
Transit Time ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Brain Oxygenation ◽  
Cerebral Metabolic Rate ◽  
Arterial Blood ◽  
Extraction Fraction

IntroductionDuring brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby reducing brain oxygenation.Methods and analysisThis is a double-blind, randomised clinical trial including 48 patients scheduled for surgical brain tumour removal. Prior to imaging and surgery, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood flow, capillary transit-time heterogeneity, cerebral blood volume, blood mean transit time, and calculated oxygen extraction fraction and cerebral metabolic rate of oxygen for negligible tissue oxygen extraction. PET measurements include cerebral metabolic rate of oxygen, cerebral blood flow and oxygen extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured.Ethics and disseminationThis study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration numberNCT02713087; Pre-results. 2015-001359-60; Pre-results.

Cerebral Blood Flow and Cerebral Metabolic Rate of Oxygen Requirements for Cerebral Function and Viability in Humans

1985 ◽  
Vol 5 (4) ◽  
pp. 600-608 ◽  
Author(s):  
William J. Powers ◽  
Robert L. Grubb ◽  
Danielle Darriet ◽  
Marcus E. Raichle
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Cerebral Blood Volume ◽  
Oxygen Extraction Fraction ◽  
Neurological Deficits ◽  
Regional Cerebral Blood ◽  
Cerebral Tissue ◽  
Cerebral Metabolic Rate ◽  
Regional Cerebral Blood Volume

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.

scholarly journals Metabolic Control of Resting Hemispheric Cerebral Blood Flow is Oxidative, not Glycolytic

2011 ◽  
Vol 31 (5) ◽  
pp. 1223-1228 ◽  
Author(s):  
William J Powers ◽  
Tom O Videen ◽  
Joanne Markham ◽  
Vonn Walter ◽  
Joel S Perlmutter
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Metabolic Control ◽  
Univariate Analysis ◽  
Oxygen Metabolism ◽  
Oxygen Extraction Fraction ◽  
Arterial Oxygen ◽  
Whole Brain ◽  
Cerebral Metabolic Rate

Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO2, CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO2 was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO2: arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO2 and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.

scholarly journals Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients

2020 ◽  
Vol 133 (2) ◽  
pp. 304-317
Author(s):  
Klaus U. Koch ◽  
Irene K. Mikkelsen ◽  
Joel Aanerud ◽  
Ulrick S. Espelund ◽  
Anna Tietze ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Oxygen Saturation ◽  
Oxygen Extraction Fraction ◽  
Cerebral Oxygen Saturation ◽  
Cerebral Oxygen ◽  
Contralateral Hemisphere ◽  
Regional Cerebral Oxygen Saturation ◽  
Cerebral Metabolic Rate

Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. Methods In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. Results Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 μmol · 100 g−1 · min−1; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 1.5 [−13.3 to 16.3] μmol · 100 g−1 · min−1 [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 μmol · 100 g−1 · min−1; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 8.2 [−2.0 to 18.5] μmol · 100 g−1 · min−1 [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g−1 · min−1 [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], −0.6 [−14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], −0.1 [− 12.1 to 12.0]% [P = 0.989]) were comparable between groups. Conclusions The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Vasopressin and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs

1990 ◽  
Vol 258 (2) ◽  
pp. H408-H413 ◽  
Author(s):  
W. M. Armstead ◽  
C. W. Leffler ◽  
D. W. Busija ◽  
R. Mirro
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Vascular Resistance ◽  
Brain Regions ◽  
Cerebral Metabolic Rate ◽  
Cerebral Vasoconstriction ◽  
Newborn Pigs ◽  
Cerebral Vascular Resistance ◽  
Cerebral Vascular

The interaction between vasopressinergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious hypotensive newborn pig was investigated. Indomethacin treatment (5 mg/kg) of hypotensive piglets caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 52 and 198% 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.58 +/- 0.32 ml.100 g-1.min-1 to 1.01 +/- 0.12 and 0.29 +/- 0.08 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Treatment with the putative vascular (V1) receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine]arginine vasopressin (MEAVP) had no effect on regional cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or during hemorrhagic hypotension. However, decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were blunted markedly in animals treated with MEAVP. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn pig, as reported previously, and implicate removal of vasopressinergic modulation by prostanoids as a potential mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

Elevated Cerebral Blood Oxygen Extraction in Non-Transfused Sickle Cell Disease Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1387-1387
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Soyoung Choi ◽  
Thomas Coates ◽  
John C Wood
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Cell Disease ◽  
T2 Relaxation ◽  
Hemoglobin S ◽  
Cerebral Metabolic Rate ◽  
Extraction Fraction

Abstract Introduction Chronic Transfusion Therapy (CTT) has been successful in decreasing stroke frequency in patients with sickle cell disease (SCD). Despite this, indication for CTT is largely based on empirical evidence and the mechanisms by which CTT protects the brain remain unclear. CTT improves oxygen carrying capacity and lowers hemoglobin S%, but the corresponding impact on cerebral blood flow(CBF), cerebral metabolic rate (CMRO2), and oxygen extraction fraction (OEF) is unknown. Understanding the impact of these competing influences in non-transfused (NT) and chronically transfused (CT) SCD patients will inform stroke prevention. Thus, we measured CBF, CMRO2, and OEF, in NT and CT patients with SCD using magnetic resonance imaging (MRI). Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fourteen (6 NT, 8 CT) patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Complete blood count and hemoglobin electrophoresis were performed. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. CaO2 was calculated as the product of hemoglobin, SaO2 and the oxygen density of hemoglobin (1.36 ml/g). Phase contrast imaging of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via previously validated calibration curves. OEF represented the difference of SaO2 andSvO2 divided bySaO2. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for brain volume calculation using BrainSuiteñ software. Results Table 1 summarizes the results. Hemoglobin and oxygen content were well matched between transfused and non transfused SCD patients. Cerebral metabolic rate was also nearly identical in the two groups. However, CT patients exhibited 25% higher CBF than NT SCD patients, allowing them to have a normal oxygen extraction fraction ~30%. In contrast, OEF in NT SCD patients was abnormally high (37.8%), suggesting a decreased extraction reserve. Total oxygenation index (TOI) by NIRS also trended lower in NT SCD patients, consistent with the greater oxygen extraction and lower cerebral venous saturations observed. Abstract 1387. TableCTL (reference)NTCTp value (NT vs CT)Hemoglobin (g/dl)13.5 ± 1.229.7 ± 1.259.7 ± 1.05nsCaO2 (umol O2/ml)9.85 ± .996.84 ± 1.176.95 ±.71nsCMRO2 (umol O2/100g/min)193.1 ± 44.9239.7 ± 35.3238.6 ± 38.3nsCBF (ml/100g/min)70.0 ± 12.8101.5 ± 16.6127.1 ± 23.5< 0.05OEF (%)30.0 ± 7.137.8. ± 3.0629.7 ± 7.53< 0.05NIRS TOI56.0 ± 4.0948.5 ± 4.2153.5 ± 8.760.076SvO2 (%)65.6 ± 6.856.2 ± 5.267.1 ± 6.7< 0.05 Discussion: Chronically transfused SCD patients achieve normal brain oxygenation metrics (SvO2, OEF, and NIRS) but require very high CBF to achieve this balance (lowering flow reserve). In contrast, NT SCD patients have smaller increases in CBF but require greater oxygen extraction to meet cerebrovascular demands (lowering extraction reserve). Hemoglobin S mediate changes in oxygen dissociation, blood viscosity, red cell deformability and microvascular damage potentially mediate these differences but their interplay is complicated and requires further study. Disclosures Coates: novartis: Consultancy, Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria; acceleron: Consultancy, Honoraria.

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