Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO(2) responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO(2) responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V(mean)), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO(2) tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO(2) responsiveness was quantified as Delta% V(mean) and Delta mu mol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO(2) tension. Both ways of measurements revealed lower cerebrovascular CO(2) responsiveness in SCD patients versus controls (V(mean), 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 Delta% V(mean) per mm Hg, P <.001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 Delta mu mol/L per mm Hg, P = .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 Delta mu mol/L per mm Hg, P = .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 Delta mu mol/L per mm Hg, P = .038). Cerebrovascular CO(2) responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO(2) responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke. (Blood. 2009;114:3473-3478)