Cardiovascular autonomic dysfunction in sickle cell anemia

Sickle cell anemia (SCA) is associated to increased cardiac output, normal heart rate (HR), abnormal QT dispersion and lower diastolic blood pressure (DBP). The mechanisms are still unknown. The objective of this study was to test the hypothesis that there is cardiovascular autonomic dysfunction (CAD) in SCA. The secondary objectives were to distinguish the roles of chronic anemia and hemoglobinopathy and to evaluate the predominance of the sympathetic or parasympathetic systems in the pathogenesis of CAD. Sixteen subjects with SCA, 13 with sickle cell trait (SCT), 13 with iron deficiency anemia (IDA), and 13 healthy volunteers (HV) were evaluated. All subjects were submitted to 24 h-electrocardiogram (24 h-ECG), plasma norepinephrine (NE) measurement before and after isometric exercise (IE), and also Valsalva maneuver (VM), diving maneuver (DV), and tilt test (TT). Baroreflex sensitivity (BRS) was also evaluated. The minimum, average and maximum HR as well as the percentage of bradycardia and tachycardia at 24-h ECG were similar in all groups. NE at baseline and after IE did not differ between groups. The SCA group showed less bradycardia at phase IV of VM, less bradycardia during DV, and also less tachycardia and lower DBP during TT. BRS for bradycardia and tachycardia reflex was decreased in the SCA and SCT groups. In conclusion, 1) there is CAD in SCA, and it is characterized by the reduction of BRS and the limitation of HR modulation mediated by the parasympathetic system; 2) cardiovascular sympathetic activity is preserved in SCA; and 3) hemoglobinopathy is the preponderant ethiopathogenic factor. (C) 2011 Elsevier B.V. All rights reserved.

The influence of hydroxyurea on oxidative stress in sickle cell anemia

OBJECTIVE: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. METHODS: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. RESULTS: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). CONCLUSION: Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals.