Endothelial-Dependent Vasodilation Is Impaired in Children with Sickle Cell Disease (SCD).

Impairment of endothelium-dependent vasodilation has been reported in steady-state SCD adult patients, and could contribute to the occurrence of vaso-occlusive events. In order to study whether vascular tone abnormalities could be also observed in SCD children, we enrolled 21 SCD steady-state children (18 homozygous SS, 3 S-b⁰ thalassemics); 12 males, 9 females, mean aged 10.4 ± 3.3 yrs, mean Hb level: 7.6 ± 1.0 g/dL. None had had a transfusion in the 3 previous months, nor were treated with hydroxyurea. These SCD children were compared to a control group of 23 Afro-Caribbean AA and AS controls matched for age and gender. Blood pressure and vascular function parameters were measured after the child had been recumbent for at least 10 minutes. Flow-mediated (FMD) and nitroglycerine-mediated (GTNMD) dilation of the brachial artery were examined in cases and controls using echotracking techniques. Additionally, intima-media thickness (IMT) and mechanical properties of the common carotid artery were measured using previously described methods.

Blood pressures in SCD and control children were comparable. IMT was not different in SCD children (0.42 ± 0.06 mm) vs controls (0.42 ± 0.03 mm). Systolic and diastolic diameters of the common carotid artery were significantly higher in SCD children than in controls (respectively, 6.8 ± 0.8 vs 5.7 ± 0.4, p<0.001, and 5.7 ±0.7 vs 5.0 ± 0.4 mm, p< 0.005) but the stiffness of the common carotid artery was not different in SCD children and in controls. Finally, FMD was significantly decreased in SCD children vs controls (5.6 ± 0.2 vs 8.0 ± 0.2 %, p: 0.008), while GTNMD was comparable in SCD patients and controls. We hypothesize that the increase of the carotid artery diameters, without modification of the distensibility, is related to the higher cardiac output secondary to anemia. Interestingly, we observed a significant decrease of the endothelial-dependent flow-mediated vasodilation in SCD children, which had never been reported before. This could result of impaired NO bioavailability, correlated with enhanced arginase activity and hemolysis rate. Oral arginine supplementation in SCD children could be an appropriate treatment.