Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias

2021 ◽  
Author(s):  
Chau Vu ◽  
Adam Bush ◽  
Soyoung Choi ◽  
Matthew Borzage ◽  
Xin Miao ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Cerebral Oxygen ◽  
Cell Disease

Cerebral Oxygen Saturation in Sickle Cell Patients Treated with Hydroxyurea:.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1677-1677
Author(s):  
Masoud Nahavandi ◽  
Fatemeh Tavakkoli ◽  
Melville Q. Wyche ◽  
Syed P. Hasan ◽  
Oswaldo Castro
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Sickle Cell ◽  
Cerebral Oxygenation ◽  
Cerebral Oximetry ◽  
Cerebral Oxygen Saturation ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Non Invasive

Abstract Recently we reported the use of a non-invasive near-infrared optical spectroscopy technique to measure cerebral oxygenation (cerebral oximetry, rSO2%) in agroup of 27 adult patients with sickle cell disease (Eur J Clin Invest, 34:143,2004). The sickle cell patients’ rSO2 values were significantly lower (mean 47.7%) than those in normal subjects (mean 61.3%) even though none of the patients had clinical evidence of stroke or cerebral ischemia. We included patients with all Hb phenotypes, and regardless of hydroxyurea (HU) treatment. Transfusions improved cerebral oxygen saturation but the post-transfusion values still did not reach normal levels. Our findings were corroborated independently by Raj et al. who studied 25 children with sickle cell disease (J Pediat Hematol Oncol 26:279,2004). In order to determine if long-term HU treatment affects rSO2, we analyzed cerebral oximetry results in a subset of 31 patients with sickle cell anemia (Hb SS). Eleven of them were on long-term (more than 6 months) HU treatment at stable doses (1000–1500 mg/day). The table shows that the mean rSO2, Hb, Hct, and MCV in HU-treated patients were significantly higher than those in sickle cell anemia (SCA) patients not on HU. The rSO2 in HU-treated patients was 12.5% higher than in SS patients not on this drug. By comparison, we previously reported a 24% increment in rSO2 following transfusions. A group of 8 patients who were on long-term HU treatment were given also single 1000 mg oral doses of HU and their rSO2 was measured for 12 hours without noticeable change in cerebral oxygenation. Nor did rSO2 change after oxygen inhalation (3L/min). The cause of the low rSO2 in sickle cell patients is unknown and still under investigation. It is probably not related exclusively to the anemia, since, as previously reported, anemic subjects without sickle cell disease appear to have normal rSO2. These preliminary results indicate that chronic HU treatment is associated with higher rSO2 values in SCA. If validated in a larger number of patients, our findings suggest that cerebral oximetry could be a useful, non-invasive method for assessing a new in vivo effect of HU and red cell transfusion in sickle cell disease: increased blood oxygen saturation in the cerebral vasculature. HYDROXYUREA AND CEREBRAL OXYGEN SATURATION IN PATIENTS WITH SICKLE CELL DISEASE NO HYDROXYUREA (N=20) HYDROXYUREA (N=11) P value* rSO2 = cerebral oxygen saturation. *= t-test. Plus/minus figures represent SD Mean rSO2 (%) 41 ± 6.6 46 ± 7.6 0.025 Mean Hb (g/dl) 8.4 ± 1.4 9.68 ± 1.2 0.029 Mean Hct (%) 24± 3.4 28± 4.4 0.027 Mean MCV (fl) 89± 8 102± 7 0.028

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.

scholarly journals PF742 CEREBRAL OXYGEN METABOLISM MEASUREMENTS WITH MRI IN ADULTS WITH SICKLE CELL DISEASE

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 324-325
Author(s):  
L. Vaclavu ◽  
E. Petersen ◽  
H. Mutsaerts ◽  
J. Petr ◽  
C. Majoie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Cerebral Oxygen Metabolism

scholarly journals Cerebral oxygen metabolism in adults with sickle cell disease

2020 ◽  
Author(s):  
Lena Václavů ◽  
Jan Petr ◽  
Esben Thade Petersen ◽  
Henri J.M.M. Mutsaerts ◽  
Charles B.L. Majoie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Cerebral Oxygen Metabolism

Resting metabolic rate in homozygous sickle cell disease

1993 ◽  
Vol 57 (1) ◽  
pp. 32-34 ◽  
Author(s):  
A Singhal ◽  
P Davies ◽  
A Sahota ◽  
P W Thomas ◽  
G R Serjeant
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Resting Metabolic Rate ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

scholarly journals Reduced Cerebral Metabolic Rate of Oxygen in Adults with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Lena Vaclavu ◽  
Esben Thade Petersen ◽  
Ed T VanBavel ◽  
Charles BL Majoie ◽  
Aart J Nederveen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Carrying Capacity ◽  
Oxygen Extraction Fraction ◽  
Healthy Controls ◽  
Cell Disease ◽  
Whole Brain ◽  
Cerebral Metabolic Rate ◽  
Oxygen Carrying Capacity

Abstract Introduction: Cerebral blood flow (CBF) is increased in sickle cell disease (SCD) to compensate for chronic hemolytic anemia. Since the brain is strongly dependent on adequate oxygen levels, severe anemia may result in ischemia and silent cerebral infarctions (SCIs), which are present in the majority of patients with SCD. Besides CBF, the cerebral metabolic rate of oxygen (CMRO2), representing the cerebral oxygen consumption, can be measured using specialized MRI techniques. CMRO2 is dependent on CBF, OEF oxygen extraction fraction (OEF) and the hematocrit in the cerebral circulation. In order to maintain stable CMRO2 the OEF changes to compensate for fluctuations in CBF. Previous studies found either elevated or reduced rather than stable CMRO2 in SCD. To further explore the regulation of cerebral oxygenation in SCD, we measured CMRO2, OEF and CBF using MRI at rest and upon administration of acetazolamide (ACZ), a non-metabolic vasodilator. In addition, we related the CMRO2 to the prevalence and location of SCIs and to laboratory parameters of hemolysis. Methods: Adult SCD patients (HbSS/HbSβ0) without a history of stroke, and healthy age-, sex, and race-matched controls were recruited for this IRB-approved MRI study with ACZ-induced vasodilation and venous blood sampling. MRI images were acquired at 3T (Philips Healthcare, Best, NL). Sequences included 3D FLAIR with 1mm isotropic resolution for lesion evaluation, longitudinal and transverse relaxation times of blood (T1b and T2b) in the cerebral sagittal sinus using a T2 prepared tissue relaxation with inversion recovery sequence (T2-TRIR), and pseudo-continuous arterial spin labeling (ASL) for whole brain CBF measurements. T1b was used to correct ASL-based CBF values. T2b was converted to venous saturation (Yv) using a recently published SCD-specific model, which was calibrated in sickle blood rather than bovine blood. CBF was measured at baseline and 10 min post acetazolamide (ACZ) (16mg/kg intravenous infusion over 3min). Images were co-registered and quantified using the ExploreASL toolbox. CMRO2 was calculated as follows: CMRO2 = CBF * OEF * Ca, where CBF is the whole brain CBF map from ASL, OEF is the arteriovenous oxygen saturation (Y) difference (Ya-Yv/Ya) derived from T2 measurements, and Ca is the oxygen carrying capacity of blood calculated from hematocrit sampled immediately prior to MRI. Blood markers of hemolysis (reticulocyte count and bilirubin) were correlated to MRI hemodynamic markers using bivariate Spearman's rho (ρ). Group comparisons were tested using Student's t-tests. P values <0.05 were considered statistically significant. Results: As expected, CBF was significantly higher in patients with SCD (69 ± 16 mL/100g/min) compared to healthy controls (42 ± 4 mL/100g/min, P <0.001), whereas oxygen carrying capacity (Ca) was significantly lower in patients with SCD vs healthy controls due to lower hematocrit (485 ± 83 vs 794 ± 66 μmol O2/100ml blood, P=0.001). At baseline, mean CMRO2 was lower in patients with SCD compared to healthy controls (88 ± 20 vs 117 ± 18 μmol/100 g/min, P = 0.002), contrary to our hypothesis, indicating a reduced oxygen metabolism in patients with SCD. After acetazolamide, CMRO2 remained the same due to an increase in CBF (P<0.001) and a compensatory reduction in OEF. The reduction in OEF in patients with SCD and healthy controls (20 ± 7 vs 19 ± 6, respectively P= 0.76) indicates that OEF adjusts appropriately according to the increased flow. By mapping CMRO2 and the locations of SCIs, we found that lesions were most prevalent in the regions with the lowest CMRO2 corresponding to the deep white matter and borderzone regions, supporting an ischemic etiology of lesions. High hemolytic rate was associated with higher CMRO2 most likely due to an increased CBF. Conclusion: We observed reduced CMRO2 in patients with SCD compared to healthy controls due to low OEF. A reduced CMRO2 could pose a risk for ischemia, despite high flow rate delivering oxygen, because of low OEF. This is supported by the fact that the silent cerebral infarcts are located in regions with the lowest CMRO2. We postulate that patients with SCD have a reduced capacity to increase the OEF in regions with inadequate CBF resulting in local ischemia and local infarction. The pathogenesis of the reduced OEF remains unclear but could be related to arteriovenous shunting whereby there is insufficient time for oxygen to dissociate. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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