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 CO2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO2 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 CO2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO2 responsiveness was quantified as Delta% V(mean) and Deltamicromol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO2 tension. Both ways of measurements revealed lower cerebrovascular CO2 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 Deltamicromol/L per mm Hg, P = .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 Deltamicromol/L per mm Hg, P = .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 Deltamicromol/L per mm Hg, P = .038). Cerebrovascular CO2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke.

Baroreflex sensitivity is higher during acute psychological stress in healthy subjects under ß-adrenergic blockade.

Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). ß-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under ß-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24-42) compared with 17 (16-28) ms·mmHg-1, P<0.05; BRSFD: 27 (20-34) compared with 14 (9-19) ms·mmHg-1, P<0.05; values are medians (interquartile range)]. BP declined after the jump in both groups, and post-jump BRS did not differ between the groups. In conclusion, during acute psychological stress, BRS is higher in healthy subjects treated with non-selective ß-adrenergic blockade with significantly lower HR but comparable BP.

Arterial wave reflection decreases gradually from supine to upright.

BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS. In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection was quantified as the augmentation index (AIx) and the reflection magnitude (RM). RESULTS. During HUT, heart rate increased (p < 0.001), stroke volume and cardiac output decreased (p < 0.001 and p < 0.01), diastolic blood pressure increased (p < 0.001), whereas systolic blood pressure did not change. TPR increased from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p < 0.001). AIx fell gradually from 25% at 0°to 16%, -1% and -10% at 30°, 70° and 90° (p < 0.001). The RM decreased from 0.572 at 0°to 0.456 at 90° (p < 0.001). CONCLUSION. From supine to upright, arterial wave reflection represented as AIx and RM gradually decreases in the presence of increasing TPR.

Dynamic cerebral autoregulation in homozygous Sickle cell disease.

BACKGROUND AND PURPOSE: Sickle cell disease (SCD) is associated with cerebral hyperperfusion and an increased risk of stroke. Also, both recurrent microvascular obstruction and chronic hemolysis affect endothelial function, potentially interfering with systemic and cerebral blood flow control. We addressed the question whether cerebrovascular control in patients with SCD is affected and related to hemolysis. METHODS: Systemic and cerebrovascular control were studied in 18 patients with SCD and 10 healthy subjects. Dynamic cerebral autoregulation was evaluated by transfer function analysis assessing the relationship between mean cerebral blood flow velocity and mean arterial pressure. RESULTS: Normal baroreflex sensitivity and postural cardiovascular reflex responses indicated integrity of systemic cardiovascular control. In the low- (0.07 to 0.15 Hz) frequency region, mean arterial pressure variability was comparable for both groups, but a larger mean cerebral blood flow velocity variability in SCD (6.1 [4.6 to 7.0] versus 4.2 [2.6 to 5.2] [cm x s(-1)](2) x Hz(-1); P<0.05) indicated a reduced capacity to buffer the transfer of blood pressure surges to the cerebral tissue. Impairment of dynamic cerebrovascular control was confirmed by a reduced mean arterial pressure-to-mean cerebral blood flow velocity transfer function phase lead in SCD versus healthy subjects (32+/-17 degrees versus 50+/-19 degrees , P<0.05) that was unrelated to the severity of hemolysis. CONCLUSIONS: In patients with SCD, dynamic cerebral autoregulation is impaired but appears unrelated to hemolysis.

Impaired nocturnal blood pressure dipping in patients with type 2 diabetes mellitus.

Hypertension is a common comorbidity of type 2 diabetes mellitus (T2DM). Both conditions are associated with an increased cardiovascular risk, which is reduced by tight blood pressure (BP) and glycemic control. However, nondipping BP status continues to be an enduring cardiovascular risk factor in T2DM. Cardiovascular autonomic neuropathy and endothelial dysfunction have been proposed as potential mechanisms. This study tested the hypothesis that microvascular disease rather than cardiovascular autonomic neuropathy interferes with the physiological nocturnal BP reduction. Cardiovascular autonomic function and baroreflex sensitivity were determined in 22 type 2 diabetic patients with (DM+) and 23 diabetic patients without (DM-) manifest microvascular disease. BP dipping status was assessed from 24-hour ambulatory BP measurements. Sixteen nondiabetic subjects served as controls (CTRL). Cardiovascular autonomic function was normal in all subjects. Baroreflex sensitivity was lower in DM- compared with CTRL (7.7 ± 3.3 vs. 12.3 ± 8.3 ms·mm Hg-1; P < 0.05) and was further reduced in DM + (4.6 ± 2.0 ms·mm Hg-1; P < 0.01 vs. DM- and CTRL). The nocturnal decline in systolic and diastolic BP was blunted in DM- (12% and 14% vs. 17% and 19% in CTRL; P < 0.05) and even more so in DM+ (8% and 11%; P < 0.05 vs. DM- and P < 0.001 vs. CTRL). A nocturnal reduction in pulse pressure was observed in CTRL and DM- but not in DM+ (P < 0.05 vs. DM- and P < 0.01 vs. CTRL). In T2DM, progression of microvascular disease interferes with the normal nocturnal BP decline and coincides with a persistently increased pulse pressure and reduced baroreflex sensitivity, contributing to their increased cardiovascular risk.

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review.

Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs). Various treatments have been evaluated over the years. However, a clear overview is lacking. The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD. Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants l-glutamine and ω-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was registered at PROSPERO (CRD42015025250).

[Concentration problem or epilepsy? Sudden changes in behaviour in adolescents]. / Concentratiestoornis of epilepsie? Adolescenten met plotselinge gedragsveranderingen.

Sudden changes in behaviour and concentration problems can be caused by non-convulsive status epilepticus. This generalised form of epilepsy can be easily missed as a diagnosis. In this case report series we describe three adolescent boys (13, 14 and 17 years old respectively) presenting with behavioural disturbances caused by idiopathic non-convulsive status epilepticus. The diagnosis was confirmed by electroencephalography (EEG). The medical history mentioned previous episodes of changes in behaviour in all patients. The 14-year-old boy was diagnosed with attention deficit hyperactivity disorder (ADHD). It is questionable whether this diagnosis was justified, or whether his behavioural problems were caused by non-convulsive epileptic seizures. Non-convulsive status epilepticus is characterised by diminished cognitive functioning in an otherwise reactive patient. Testing of memory and other cognitive functions is essential for diagnosis. All children with behavioural problems should undergo a thorough neurological assessment by a paediatrician or neurologist in order to recognise non-convulsive epilepsy.

Intensive blood pressure control affects cerebral blood flow in type 2 diabetes mellitus patients.

Type 2 diabetes mellitus is associated with microvascular complications, hypertension, and impaired dynamic cerebral autoregulation. Intensive blood pressure (BP) control in hypertensive type 2 diabetic patients reduces their risk of stroke but may affect cerebral perfusion. Systemic hemodynamic variables and transcranial Doppler-determined cerebral blood flow velocity (CBFV), cerebral CO2 responsiveness, and cognitive function were determined after 3 and 6 months of intensive BP control in 17 type 2 diabetic patients with microvascular complications (T2DM+), in 18 diabetic patients without (T2DM-) microvascular complications, and in 16 nondiabetic hypertensive patients. Cerebrovascular reserve capacity was lower in T2DM+ versus T2DM- and nondiabetic hypertensive patients (4.6±1.1 versus 6.0±1.6 [P<0.05] and 6.6±1.7 [P<0.01], Δ%mean CBFV/mm Hg). After 6 months, the attained BP was comparable among the 3 groups. However, in contrast to nondiabetic hypertensive patients, intensive BP control reduced CBFV in T2DM- (58±9 to 54±12 cm·s(-1)) and T2DM+ (57±13 to 52±11 cm·s(-1)) at 3 months, but CBFV returned to baseline at 6 months only in T2DM-, whereas the reduction in CBFV progressed in T2DM+ (to 48±8 cm·s(-1)). Cognitive function did not change during the 6 months. Static cerebrovascular autoregulation appears to be impaired in type 2 diabetes mellitus, with a transient reduction in CBFV in uncomplicated diabetic patients on tight BP control, but with a progressive reduction in CBFV in diabetic patients with microvascular complications, indicating that maintenance of cerebral perfusion during BP treatment depends on the progression of microvascular disease. We suggest that BP treatment should be individualized, aiming at a balance between BP reduction and maintenance of CBFV.

Active standing reduces wave reflection in the presence of increased peripheral resistance in young and old healthy individuals.

OBJECTIVE: Pressure wave reflections are age-dependent and generally assumed to increase with increasing peripheral resistance. We sought to determine the effect of standing on wave reflection in healthy older and younger individuals and the influence of increased peripheral resistance. METHODS: During supine rest and active standing, continuous finger arterial blood pressure was measured. Data obtained in the supine period and after 1 and 5 min standing were analysed. Aortic pressure and flow, calculated from finger pressure, were used to derive forward and backward pressure waves, reflection magnitude (ratio of backward and forward pressure waves), augmentation index, and peripheral resistance. RESULTS: Fifteen healthy older (aged 53±7 years) and 15 healthy younger (aged 29±5 years) individuals were included. In both groups, upon standing, stroke volume, cardiac output and pulse pressure decreased with an increase in heart rate and in diastolic pressure. In the older group peripheral resistance increased from 1.3±0.4 to 1.5±0.4 and 1.5±0.4 for supine, 1 and 5 min standing, whereas reflection magnitude decreased from 0.67±0.1 to 0.61±0.1 and 0.61±0.1, and augmentation index from 33±11 to 23±12 and 25±11. In the younger group peripheral resistance increased from 0.9±0.2 to 1.1±0.2 and 1.1±0.2, whereas reflection magnitude decreased from 0.55±0.05 to 0.48±0.05 and 0.49±0.05 and augmentation index from 18±11 to 1±18 and 4±19. CONCLUSION: With standing, haemodynamic variables change similarly in older and younger individuals. The opposite changes in reflection magnitude and peripheral resistance suggest that reflection and pressure augmentation are not solely dependent on peripheral resistance.