Sickle cell disease (SCD) is the most common cause of
stroke in childhood and results primarily from a mismatch of cerebral
oxygen supply and demand rather than arterial obstruction. However, resting cerebral blood flow (CBF) has not been examined in the general African American population, in whom
obesity,
hypertension,
cerebrovascular disease, and diminished cerebrovascular reserve capacity are common. To better understand the underlying physiological substrate upon which SCD is superimposed, we measured CBF in 32 young (age 28 ± 10 yr), asymptomatic African American subjects with and without
sickle cell trait (n= 14). To characterize the effects of chronic
anemia, in isolation of
sickle hemoglobin we also studied a cohort of 13 subjects with
thalassemia major (n= 10), dyserythropoetic
anemia (n= 1), or spherocytosis (n= 2). Blood was analyzed for complete blood count,
hemoglobin electrophoresis, cell free
hemoglobin, and
lactate dehydrogenase. Multivariate regression analysis showed that
oxygen content was the strongest predictor of CBF (r(2)= 0.33,P< 0.001). CBF declined rapidly in the second and third decades of life, but this drop was explained by reductions in cerebral gray matter. However, age effects persisted after correction for brain composition, possibly representing microvascular impairment. CBF was independent of viscosity,
hemoglobin S%, and body mass index.
Hyperoxia resulted in reduced CBF by 12.6% (P= 0.0002), and CBF changes were proportional to baseline
oxygen content (r(2)= 0.16,P= 0.02). These data suggest that these
hemoglobin subtypes do not alter the normal CBF regulation of the balance of
oxygen supply and demand.