TY - JOUR
T1 - Cerebral oxygen metabolism in adults with sickle cell disease
AU - Václavů, Lena
AU - Petr, Jan
AU - Petersen, Esben Thade
AU - Mutsaerts, Henri J.M.M.
AU - Majoie, Charles B.L.
AU - Wood, John C.
AU - VanBavel, Ed
AU - Nederveen, Aart J.
AU - Biemond, Bart J.
N1 - Funding Information: Funding: Fonds Nuts Ohra grant no. 1303‐055. Publisher Copyright: © 2020 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
PY - 2020/4
Y1 - 2020/4
N2 - In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2. CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2-prepared tissue relaxation with inversion recovery (T2-TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P <.001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 μmol O2/100g/min, P =.69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P <.001), resulting in lower CMRO2 in patients versus controls (102 ± 24 versus 127 ± 20 μmol O2/100g/min, P =.002). After acetazolamide, CMRO2 declined further in patients (P <.01) and did not decline significantly in controls (P =.78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.
AB - In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2. CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2-prepared tissue relaxation with inversion recovery (T2-TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P <.001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 μmol O2/100g/min, P =.69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P <.001), resulting in lower CMRO2 in patients versus controls (102 ± 24 versus 127 ± 20 μmol O2/100g/min, P =.002). After acetazolamide, CMRO2 declined further in patients (P <.01) and did not decline significantly in controls (P =.78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.
KW - Acetazolamide/pharmacology
KW - Adult
KW - Anemia, Sickle Cell/blood
KW - Brain Ischemia/etiology
KW - Brain/diagnostic imaging
KW - Cerebrovascular Circulation/drug effects
KW - Cross-Sectional Studies
KW - Female
KW - Fetal Hemoglobin/analysis
KW - Humans
KW - Hydroxyurea/therapeutic use
KW - Hypoxia, Brain/diagnostic imaging
KW - Magnetic Resonance Imaging
KW - Male
KW - Middle Aged
KW - Neuroimaging
KW - Oxygen Consumption
KW - Oxygen/metabolism
KW - Treatment Failure
KW - Vasodilator Agents/pharmacology
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85078656014&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajh.25727
DO - https://doi.org/10.1002/ajh.25727
M3 - Article
C2 - 31919876
SN - 0361-8609
VL - 95
SP - 401
EP - 412
JO - American journal of hematology
JF - American journal of hematology
IS - 4
ER -