Georgios Settakis

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature

Pathologic processes affecting the brain vessels may damage cerebral vasodilatory capacity. Early detection of cerebral dysfunction plays an important role in the prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has frequently been used for this purpose. In the present work the mechanism of action and the previous studies are reviewed. The authors conclude that AZ tests are useful in cerebrovascular research. Further investigations are recommended to prove how impaired reserve capacity and reactivity influence the stroke risk in patients and whether these tests may indicate therapeutic interventions.

Transcranial Doppler Study of the Cerebral Hemodynamic Changes During Breath-Holding and Hyperventilation Tests

Background and purpose. The aim of the present study was to assess the time course of hyperventilation (HV) and breath‐holding (BH) tests in healthy volunteers. Subjects and Methods. Young healthy volunteers (n= 29) underwent continuous registration of the middle cerebral artery mean blood flow velocity (MCAV) during and after 30 seconds of BH and 60 seconds of HV. Absolute values as well as percentage changes of the MCAV are reported. In 13 subjects, determination of capillary blood gas parameters (pH, pCO2, pO2, and O2 saturation) was performed before tests, after BH and after HV. Results. MCAV during 30 seconds of breath‐holding starts to increase after 10 seconds and reaches its highest level at 30 seconds. After breathing normally, MCAV normalizes within 30 seconds. Hyper‐ ventilation results in a decrease in MCAV, which reaches a plateau at 20 to 30 seconds after starting to hyperventilate, and blood flow velocity did not change significantly any further until the end of the procedure. The normalization of the MCAV is incomplete at 30 seconds after finishing hyperventilation. None of the capillary blood gases changed significantly after breathholding, whereas capillary pH, pO2, and oxygen saturation increased and pCO2 decreased after hyperventilation. No relationship was found between capillary blood gas parameters and MCAV values. Conclusions. The authors concluded that breathholding and hyperventilation tests seem to be a practical alternative to acetazolamide and the CO2 inhalation method in the assessment of cerebral hemodynamics.

Increased common carotid artery intima media thickness in adolescent hypertension: Results from the Debrecen Hypertension Study

Background: The aim of the present work was to investigate intima media thickness (IMT) in healthy and in hypertensive adolescents and its influencing factors. Methods: 103 hypertensive and 58 healthy adolescents were studied. IMT was measured in the common carotid artery using B-mode ultrasonography. Additionally, laboratory parameters (blood glucose, cholesterol, triglycerides, HDL- and LDL-cholesterols) and left ventricular mass indices were obtained. Results: IMT in the common carotid artery was higher in hypertensive adolescents (means ± SD: 0.55 ± 0.11 mm) than in healthy control subjects (0.48 ± 0.08 mm, p < 0.001). Similarly, a higher left ventricular mass index was measured in hypertensive (103.2 ± 30.6 g/m2) than in healthy teenagers (91.1 ± 25.2 g/m2, p < 0.001). In general, IMT in adolescents was associated with age, weight, body mass index, left ventricular mass index and average systolic and diastolic blood pressure values of the subjects. By assessing the multivariate association between IMT and other factors, intima-media thickness was only associated with age and left ventricular mass index of the hypertensive subjects and was independent from all the investigated factors in normotensive controls. Conclusions: Our data suggest an ongoing target-organ damage in adolescent hypertension. These patients need to be subjected to early diagnostic methods, treatment and a regular follow-up, in order to avoid severe clinical manifestations of secondary target-organ damage due to hypertension.

Cerebrovascular Reactivity in Hypertensive and Healthy Adolescents: TCD With Vasodilatory Challenge

Background. Adolescent hypertension predicts hypertension and increased cardiovascular morbidity in adulthood. The aim of the present work was to test whether cerebrovascular reactivity to CO2 is altered among hypertensive adolescents. Methods. From the population‐based cohort of the Debrecen Hypertension Study, 113 hypertensive and 58 normotensive adolescents underwent transcranial Doppler measurements at rest and after 30 seconds of breath holding. Results. Systolic, mean, and diastolic blood flow velocities were higher among hypertensive individuals at rest. Taking the absolute blood flow velocity parameters into account, after breath holding, only the pulsatility index was significantly higher in the hypertensive group. The percentage change of the different blood flow parameters showed less intensive change in hypertensive teenagers. Conclusion. Cerebral vasoreactivity is decreased among hypertensive individuals as compared to healthy controls.

Hyperventilation-induced cerebrovascular reactivity among hypertensive and healthy adolescents

Background: It is known that cerebral vasoreactivity is altered in adult arterial hypertension but no information is available about cerebral arteriolar function in hypertensive adolescents. Therefore, the aim of the present work was to assess cerebral vasoreactivity responses in adolescent hypertension. Methods: 113 hypertensive and 58 normotensive adolescents were assessed with transcranial Doppler sonography by using voluntary hyperventilation (HV) as vasoconstrictory stimulus. Absolute blood flow velocities (systolic, mean and diastolic) and pulsatility indices (PIs) at rest and after HV, as well as percentage change of the blood flow velocities after HV were compared among the groups. Results: Blood flow velocities at rest were significantly higher in hypertensive individuals, while PIs were similar in the two groups. After HV, all blood flow velocity parameters were higher among hypertensive teenagers than in healthy controls, while PIs did not differ between the two groups. Taking the relative changes after HV into account, it was found that HV induced a more pronounced change of the systolic and mean blood flow velocities of the control subjects than in hypertensive adolescents. Conclusions: Cerebrovascular reactivity to hypocapnia is decreased in hypertensive adolescents as compared to healthy teenagers. Further studies are needed to clarify the clinical significance of altered cerebral microvascular function in adolescent hypertension.

Assessment of cerebrovascular reserve capacity in asymptomatic and symptomatic hemodynamically significant carotid stenoses and occlusions.

BACKGROUND Cerebrovascular reactivity measurements are believed to be a helpful tool for selecting patients who are at higher risk for hemodynamic strokes. The aim of this study was to compare cerebral vasoreactivity among patients suffering from internal carotid artery stenosis of different severity (asymptomatic stenosis, asymptomatic occlusion, symptomatic stenosis, symptomatic occlusion). METHODS Sixty-two patients with asymptomatic and symptomatic internal carotid artery stenoses and occlusions underwent transcranial Doppler-acetazolamide tests. Absolute velocities of the middle cerebral arteries (MCAV), percent increases of the MCAV at different time points of the test (cerebrovascular reactivity, CVR) and maximal percent increase after administration of acetazolamide (cerebrovascular reserve, CRC) were compared on the affected and non-affected sides. Asymmetry indices (CRC (affected side)/CRC (non-affected side)) were compared between the groups of different severity of obstructive lesion. RESULTS Resting MCAV was similar on both sides in all groups. A significant side-difference of the MCAV values after acetazolamide was observed only in the symptomatic groups. Difference of cerebrovascular reserve capacity between the affected and non-affected side was statistically significant only in the symptomatic groups (CRC symptomatic stenosis 36.6 +/- 20.9% vs. 71.1 +/- 27.9%, CRC symptomatic occlusion: 31.2 +/- 24.6% vs. 64.5 +/- 29.7%). Asymmetry index of the CRC was near to 1 in the asymptomatic stenosis group only, while in all the other groups this index referred to a significant hemispheric asymmetry of the vasoreactivity. CONCLUSIONS Although in general cerebrovascular reserve capacity is compromised in cases of hemodynamically significant carotid lesions, there is a large individual variability within the subgroups. Further randomized studies are needed to clarify whether the clinical efficiency of carotid endarterectomy and extra-intracranial bypass may be improved by selecting the patients using hemodynamic criteria.

Target-organ damage in adolescent hypertension. Analysis of potential influencing factors, especially nitric oxide and endothelin-1

BACKGROUND AND PURPOSE To assess the role of the nitric oxide-endothelin imbalance in the development of target-organ damages (carotid intima-media thickness and left ventricular mass index) in adolescent hypertension. METHODS 125 adolescents--67 hypertensive and 58 normotensive--underwent routine anthropology (height, weight) and blood pressure measurements, and laboratory (glucose, cholesterol and triglyceride levels) testing as well as sampling blood for determination of the plasma concentrations of nitric oxide (NOx) and endothelin-1 (ET-1), followed by measurement of the carotid intima-media thickness (IMT) and left ventricular mass index (LVMI). RESULTS Plasma concentration of NOx was significantly lower (27.7+/-13.7 vs. 35.8+/-7.0 micromol/l, respectively, p<0.001) and ET-1 was higher (3.11+/-3.9 vs. 1.09+/-1.07 fmol/ml, respectively, p<0.001) in hypertensive adolescents than that of controls. NOx negatively, endothelin positively correlated with blood pressure values, especially with systolic BP. An inverse relationship has been found between NOx and ET-1 concentrations (r=-0.29, p<0.003). In this adolescent population body weight, systolic blood pressure and plasma ET-1 were the most important factors influencing IMT, whereas LVMI correlated with height and weight and systolic BP of the teenagers. CONCLUSIONS NO/endothelin imbalance seems to play a role in the development of hypertension and target-organ damages in adolescence. Further studies are encouraged in order to clarify the pathophysiological role of NO/endothelin imbalance in adolescent hypertension.

Effect of sevoflurane on cerebral blood flow and cerebrovascular resistance at surgical level of anaesthesia: a transcranial Doppler study

Background and objective: It is widely accepted that sevoflurane affects cerebral circulation, but there are uncertainities regarding the magnitude of its effect. The aim of the present work was to assess the effect of sevoflurane on the cerebral circulation at surgical levels of anaesthesia. Methods: Twenty patients undergoing elective lumbar discectomies were investigated. Anaesthesia was induced with propofol and maintained with sevoflurane. The level of surgical anaesthesia was determined by bispectral index, the target level was 45–55. Transcranial Doppler (TCD) measurement was performed before induction and after reaching the surgical level of anaesthesia. Besides routine parameters (middle cerebral artery mean blood flow velocity (MCAV) and pulsatility index (PI)) derived parameters (estimated cerebral perfusion pressure (eCPP), cerebral blood flow index (CBFI) and resistance area product (RAP)) were calculated by taking changes of mean arterial pressure also into account. Results: MCAV decreased from 54.1 ± 13.3 to 43.7 ± 18.5 cm s−1, P < 0.01 and PI increased from 0.79 ± 0.2 to 0.92 ± 0.2, P < 0.01 after reaching the surgical level of anaesthesia. As a result eCPP decreased by 18.2%, CBFI by 25.5% and RAP increased by 15% respectively. Conclusions: Our data indicate a vasodilatory effect of sevoflurane at surgical level of anaesthesia on large cerebral vessels or a vasoconstriction of the resistance arterioles likely caused by decreased brain metabolism.

Gender-Related Differences in Adolescent Hypertension and in Target Organ Effects

AIMS To assess whether a gender difference exists in adolescent hypertension and its target organ damage and to compare potential confounding factors and target organ damage in hypertensive and normotensive adolescent girls. METHODS From the Debrecen Hypertension Study, the anthropometric, blood pressure, and laboratory data as well as intima-media thickness (IMT) and left ventricular mass index (LVMI) of 58 hypertensive boys, 56 hypertensive girls, and 30 normotensive girls were analyzed. RESULTS Both systolic and mean blood pressure values were higher in adolescent hypertensive boys than in girls. This difference was also present when comparing 24-hour average blood pressure values. Plasma concentrations of nitric oxide (NO) and endothelin-1 were not different in the two gender groups. IMT of the carotid arteries were similar in hypertensive boys and girls, but a significantly higher LVMI was detected in boys. A significant difference was detected in anthropometric data (height, weight, and body mass index [BMI]), plasma concentration of NO (lower levels in hypertensives), and IMT in hypertensive and normotensive girls (higher IMT in hypertensive girls). CONCLUSIONS There is a difference between the severity of hypertension between hypertensive adolescent girls and boys. Hypertensive girls differ from normotensive girls not only in blood pressure values but also in risk factors and subclinical target organ effects. Further studies are needed to explain the gender differences in adolescent hypertension. The potential role of sex hormones in hypertensive teenagers also needs to be clarified in future works.