Vasoconstriction Response to Mental Stress in Sickle Cell Disease: The Role of the Cardiac and Vascular Baroreflexes

Abstract

Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R–R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the “sequence” and “spectral” techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events.

Natural history of blood pressure in sickle cell disease pregnancy

“…7,15 Many cardiovascular adaptations of pregnancy are mediated by vascular signalling changes. 16,17 People with SCD have well described vascular damage and aberrant vascular responsiveness 18,19 which may limit their physiological adaptations to pregnancy. Previous studies have demonstrated abnormally low prostaglandin to thromboxane ratios during pregnancy in people with HbSS compared to unaffected pregnancies.…”

Brain network hypersensitivity underlies pain crises in sickle cell disease

“…The frequency of VOCs varies widely across SCD individuals with a recent systematic review reporting a range of 0–18 per year 2 . Recent studies suggest that the occurrence of VOCs is associated with abnormal vasoconstriction patterns resulting from dysfunction of the autonomic nervous system, endothelial dysfunction, and/or psychological stress 3 – 5 . Central nervous system (CNS) factors may also contribute to VOCs.…”

Brain network hypersensitivity underlies pain crises in sickle cell disease

“…The frequency of VOCs varies widely across SCD individuals with a recent systematic review reporting a range of 0 to 18 per year [48]. Recent studies suggest that the occurrence of VOCs is associated with abnormal vasoconstriction patterns resulting from dysfunction of the autonomic nervous system, endothelial dysfunction, and/or psychological stress [8,40,43]. Central nervous system (CNS) factors may also contribute to VOCs.…”