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Objective: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH)., Design: Case-control study on patients with VVS and healthy controls., Methods: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation., Results: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 μg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate., Conclusion: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: Vasovagal syncope (VVS) in children and adolescents is a common disorder. There may be an internal relationship between creatine kinase (CK) and its isoenzymes (CKMB) and syncope. The aim of this study was to evaluate the changes of CK and CKMB in children and adolescents with VVS., Methods and Results: The VVS group included 218 patients (93 male and 125 female). The control group included 129 healthy children (78 male and 51 female). Serum CK and CKMB levels were estimated. We founded ①Serum CK and CK-MB levels decreased in VVS group than that in control group (P < 0.05). ②The CK levels of female were significantly lower than those of male in VVS group (P < 0.05). ③Serum level of CK-MB were in negative correlation with age, height, weight, BMI whereas in positively correlation with HR. ④CK was effected by CK-MB (β = 0.147, P = 0.037) while CK-MB was independently influenced by age (β = -0.203, P = 0.002) and DBP (β = 0.171, P = 0.011). ⑤Both CK and CK-MB significantly influenced on VVS occurrence after adjusting for the effects of gender, age, height, weight, BMI and HR., Conclusion: The serum CK and CKMB levels decrease in children and adolescents with VVS. CK and CK-MB are the independent protective factors with VVS., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope., Methods: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope., Results: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm 3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope., Conclusion: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope., (© 2019 Wiley Periodicals, Inc.)

Background and Objectives : Vasovagal syncope (VVS) is the most common cause of syncope and has multiple pathophysiological mechanisms. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide (NO). In this study, we aimed to investigate the relationship between plasma ADMA levels and syncope during the head-up tilt (HUT) test. Materials and Methods : Overall, 97 patients were included in this study. They were above 18 years of age and were admitted to our clinic with the complaint of at least one episode of syncope consistent with VVS. The HUT test was performed in all patients. Patients were divided into the following two groups based on the HUT test results: group 1 included 57 patients with a positive HUT test and group 2 included 35 patients with a negative HUT test. Blood samples were taken before and immediately after the HUT test to measure ADMA levels. Results : No significant intergroup differences were observed concerning gender and age (female gender 68% vs 60%; mean age 24.85 ± 4.01 vs 25.62 ± 3.54 years, respectively, for groups 1 and 2). ADMA values were similar between groups 1 and 2 before the HUT test [ADMA of 958 (544-1418) vs 951 (519-1269); p = 0.794]. In the negative HUT group, no significant differences were observed in ADMA levels before and after the HUT test [ADMA of 951 (519-1269) vs 951 (519-1566); p = 0.764]. However, in the positive HUT group, ADMA levels were significantly decreased following the HUT test [pretest ADMA of 958 (544-1418) vs post-test ADMA of 115 (67-198); p < 0.001]. Conclusion : ADMA levels significantly decreased after the HUT test in patients with VVS., Competing Interests: The authors have no conflict of interests to disclose.

Troponin release following exertional vasovagal syncope has not previously been reported. A young man was investigated after being admitted twice with exertional syncope, each time followed by a 10-fold spike in troponin I over 24 h. Treadmill exercise tests reproduced his symptoms and demonstrated a vasovagal mechanism. During recovery, despite lying supine, he remained hypotensive for 5 min, with profound bradycardia and ST segment depression. We suspected that intense cardiovagal neural activity may have caused the troponin leak., (© 2019 Royal Australasian College of Physicians.)

Aims: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients., Methods and Results: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group., Conclusion: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system., Competing Interests: The authors have declared that no competing interests exist.

Background Vasovagal reflex is the most common form of syncope, but the pathophysiological mechanisms that initiate the reflex are not well understood. We aimed to study supine and early orthostatic levels of the neurohormones involved in control of circulatory homeostasis in relation to the onset of tilt-induced vasovagal syncope (VVS). Methods and Results A total of 827 patients who were investigated for unexplained syncope with head-up tilt test (HUT) and optional nitroglycerin provocation (Italian protocol) had blood samples collected while supine and after 3-minutes of HUT. Of these, 173 (20.9%) patients developed VVS during drug-free HUT, 161 of whom (males 44.7%; age 45±21 years) had complete data. We analyzed levels of epinephrine, norepinephrine, C-terminal pro-arginine vasopressin, C-terminal endothelin-1, and midregional fragments of pro-atrial natriuretic peptide and pro-adrenomedullin in relation to time from tilt-up to onset of VVS. We applied a linear regression model adjusted for age and sex. The mean time to syncope was 11±7 minutes. Older age (β=0.13; SE=0.03, P<0.001), higher supine systolic blood pressure (β=0.06; SE=0.03, P=0.02), and higher supine midregional fragment of pro-adrenomedullin predicted longer time to syncope (β=2.31; SE=0.77, P=0.003), whereas supine levels of other neurohormones were not associated with time to syncope. Among 151 patients who developed VVS later than 3 minutes of HUT, increase in epinephrine (β=-3.24; SE=0.78, P<0.001) and C-terminal pro-arginine vasopressin (β=-2.07; SE=0.61, P=0.001) at 3 minutes of HUT were related to shorter time to syncope. Conclusions Older age, higher blood pressure, and higher level of pro-adrenomedullin are associated with later onset of VVS during tilt testing, whereas greater increase of tilt-induced epinephrine and vasopressin release correlate with shorter time to syncope.

Background: Head-up tilt (HUT) is widely used for diagnostic evaluation of patients with suspected vasovagal syncope (VVS), but also offers an opportunity to study VVS pathophysiology. In this regard, it is known that plasma epinephrine (Epi) levels and Epi/norepinephrine (NE) ratio are markedly increased from baseline at the time of HUT-induced VVS. However, whether these changes contribute to VVS susceptibility remains uncertain., Objective: We hypothesized that if catecholamines contributed to VVS directly, then a greater increase of plasma Epi and Epi/NE ratio early during HUT would be associated with shorter time to syncope., Methods: The patient population comprised 33 individuals (14 men, 43 ± 2 years) with suspected VVS in whom 70° HUT reproduced symptoms. Arterial Epi and NE concentrations were collected at baseline (supine) and 2 minutes of HUT. Linear, exponential, and multiple regression were used to access the association between changing catecholamine levels and time to syncope., Results: Mean ± SD time to positive HUT was 11 (7.6) minutes. Higher plasma Epi levels (pg/mL) both at baseline and at 2 minutes upright correlated with shorter time to syncope (baseline, R = -0.35, P = 0.048; and 2 minutes, R = -0.58, P = 0.001). Similarly, a greater Epi/NE ratio at 2 minutes head-up correlated with earlier time to syncope (R = -0.49, P = 0.007). These relationships remained significant after adjusting for age and sex (P = 0.006 and 0.02, respectively)., Conclusion: Greater Epi levels and Epi/NE ratio early during HUT were associated with shorter time to VVS, suggesting a possible contribution to VVS susceptibility., (© 2018 Wiley Periodicals, Inc.)

Objective: To compare the curative effect and the changes of serum electrolytes between oral rehydration salts (ORS) I and ORS III treatment in neurally mediated syncope children.
 Methods: The children with the symptom of unexplained syncope and pre-syncope were collected in Second Xiangya Hospital from May 2014 to May 2017. After head-up tilt test (HUTT), their serum electrolytes levels were examined. Children who were positive in the HUTT received ORS (ORS I or ORS III) and health education. Subjects were randomly divided into an ORS I group (n=27) and an ORS III group (n=49).
 Results: There was no statistical significance in sex, age, height, body mass, initial diagnosis and re-diagnosis interval between the 2 groups (P>0.05); the total efficiency after ORS III and ORS I 
treatment were 79.59% and 62.96%, respectively, with no statistical significance (χ2=2.483, P>0.05); the HUTT negative conversion rate after ORS III and ORS I treatment were 51.02% and 48.16%, respectively, with no statistical significance (χ2=0.058, P>0.05); before treatment, the serum sodium [(140.20±2.26) mmol/L vs (138.39±2.72) mmol/L; t=2.856, P<0.05] in the ORS III group was higher than that in the ORS I group, the serum phosphorus [(1.46±0.19) mmol/L 
vs (1.65±0.29) mmol/L; t=3.146, P<0.05] in the ORS III group was lower than that in the ORS I 
group; after treatment, the serum sodium [(140.31±2.01) mmol/L vs (138.88±2.08) mmol/L; 
t=2.692, P<0.05] and serum calcium [(2.31±0.09) mmol/L vs (2.24±0.11) mmol/L; t=2.696, P<0.05] in the ORS III group were higher than those in the ORS I group, the serum phosphorus [(1.45±0.16) mmol/L vs (1.61±0.25) mmol/L; t=3.128, P<0.05] in the ORS III group was lower than that in the ORS I group; after ORS III treatment, there was no statistical significance in serum electrolytes between HUTT positive group and HUTT negative group (P>0.05); after ORS I treatment, the serum calcium [(2.29±0.10) mmol/L vs (2.19±0.10) mmol/L; t=2.501, P<0.05] and serum phosphorus [(1.71±0.24) mmol/L vs (1.50±0.21) mmol/L; t=2.392, P<0.05] in HUTT positive group were higher than those in HUTT negative group. There was no statistical significance in serum sodium, potassium, magnesium, and chloride (P>0.05); there was no statistical significance in serum electrolytes between pre-treatment and post-treatment in the ORS I group and the ORS III 
group (P>0.05); there was no statistical significance in serum electrolytes between vasovagal syncope and postural orthostatic tachycardia syndrome in the ORS I group and the ORS III 
group before ORS treatment (P>0.05). 
 Conclusion: The ORS III and ORS I have the similar efficacy in the treatment of children with neurally mediated syncope. ORS III is easier to be accepted by children than ORS I, with better compliance.

Background and Objectives: The present study aims to determine the serum vitamin B-12 in children presenting with vasovagal syncope., Methods and Study Design: This is a prospective review of 160 children presenting with vasovagal syncope. Subgroup analysis was done based on the results of head up tilt test., Results: Head up tilt test gave positive results in 80 children and yielded negative results in the remaining 80 children. The tilt test positive children had significantly lower thyroid stimulating hormone concentrations (p=0.06), total iron binding capacity (p=0.04) and serum vitamin B-12 (p=0.01). The prevalence of vitamin B-12 deficiency was significantly higher in the tilt positive group (80% vs 52.5%, p=0.001). Out of 80 children with positive tilt test, 8 children (10%) showed cardioinhibitory response, 22 children (27.5%) demonstrated a vasodepressor response, 24 children (30%) displayed mixed response and 26 children (32.5%) had the postural orthostatic tachycardia syndrome. Erythrocyte sedimentation rate was significantly lower in the mixed response group than in the vasodepressor group (6.2±0.8 mm/h vs 14.3±2.5 mm/h, p=0.001). Serum vitamin B-12 was significantly lower in the postural orthostatic tachycardia syndrome (POTS) group than in the vasodepressor group (240.8±38.2 pg/mL vs 392.7±27.1 pg/mL, p=0.001). The prevalence of vitamin B-12 deficiency was significantly higher in the POTS group than in the vasodepressor group (92.3% vs 45.5%, p=0.001)., Conclusions: Vitamin B-12 deficiency causes reduction in myelinization, deceleration in nerve conduction and elevation in serum concentrations of noradrenaline. These factors may contribute to the impairment of autonomic functions which are involved in the pathogenesis of vasovagal syncope.

Background: Vasovagal syncope (VVS) is the most common cause of syncope in children. Neuropeptide Y (NPY) plays an important role in the regulation of blood pressure (BP), as well as myocardial contractility. This study aimed to explore the role of plasma NPY in VVS in children., Methods: Fifty-six children who were diagnosed with VVS (VVS group) using head-up tilt test (HUT) and 31 healthy children who were selected as controls (control group) were enrolled. Plasma NPY concentrations were detected. The independent t-test was used to compare the data of the VVS group with those of the control group. The changes in plasma NPY levels in the VVS group during the HUT, as well as hemodynamic parameters, such as heart rate (HR), BP, total peripheral vascular resistance (TPVR), and cardiac output (CO), were evaluated using the paired t-test. Furthermore, the correlations between plasma NPY levels and hemodynamic parameters were analyzed using bivariate correlation analysis., Results: The BP, HR, and plasma NPY (0.34 ± 0.12 pg/ml vs. 0.46 ± 0.13 pg/ml) levels in the supine position were statistically low in the VVS group compared to levels in the control group (all P < 0.05). Plasma NPY levels were positively correlated with the HR (Pearson, R = 0.395, P < 0.001) and diastolic BP (Pearson, R = 0.311, P = 0.003) when patients were in the supine position. When patients in the VVS group were in the supine position, elevated TPVR (4.6 ± 3.7 mmHg·min-1·L-1 vs. 2.5 ± 1.0 mmHg·min-1·L-1, respectively, P < 0.001; 1 mmHg = 0.133 kPa) and reduced CO (1.0 ± 0.7 L/min vs. 2.4 ± 1.3 L/min, respectively, P < 0.001) were observed in the positive-response period compared with baseline values. The plasma NPY levels were positively correlated with TPVR (Spearman, R = 0.294, P = 0.028) but negatively correlated with CO in the positive-response period during HUT (Spearman, R = -0.318, P = 0.017)., Conclusions: Plasma NPY may contribute to the pathogenesis of VVS by increasing the TPVR and decreasing the CO during orthostatic regulation.

Objectives: The aim of the present study was to explore the predictive value of red cell distribution width as a means to differentiate between neurally mediated syncope and arrhythmic syncope in children., Method: Patients were divided into a neurally mediated syncope group (n=72) and an arrhythmic syncope group (n=21) on the basis of clinical history, results of the head-up tilt test, electrocardiography, and 24-hour ambulatory electrocardiography. As controls, we recruited 55 healthy children. Red cell distribution width was determined for children in all groups. A receiver operating characteristic curve was drawn to study the predictive effect of red cell distribution width to differentiate between neurally mediated syncope and arrhythmic syncope., Results: Red cell distribution width was significantly higher in children with neurally mediated syncope than in children with arrhythmic syncope and the control group. A receiver operating characteristic curve on the predictive value of red cell distribution width in differentiating neurally mediated syncope from arrhythmic syncope showed that the area under the curve was 0.841 (95% confidence interval: 0.737-0.945, p<0.05). A red cell distribution width value of 12.8% as the cut-off value yielded a sensitivity of 80.6% and a specificity of 76.2% in discriminating between patients with neurally mediated syncope and arrhythmic syncope., Conclusion: Red cell distribution width value of ⩾12.8% might be a useful adjunct for primary-care physicians to differentiate neurally mediated syncope from arrhythmic syncope in children.

Background and Purpose: Vasovagal syncope (VVS) is linked to more than one pathophysiologic mechanisms. Copeptin, an emerging cardiovascular marker, is a surrogate for arginine-vasopressin, which increases following VVS. We aimed to assess the dynamic pattern of copeptin levels in typical VVS, categorized by the degree of vasoconstriction during orthostasis, and healthy controls., Methods: The following groups were studied: Group A (n=21), with adequate limb vasoconstriction during the first min. of tilt, assessed by limb plethysmography (at least 30% flow reduction); Group B (n=15), showing impaired vasoconstriction during orthostasis (<10% reduction); Group C (n=18), history of VVS and negative tilt test result; Group D (n=18), healthy controls. Copeptin plasma levels were assessed before and 5min following tilt test positivity or termination., Results: Baseline copeptin values were similar in all groups (8.3±6.4 in Group A, 5.7±2.3pmol/l in B, 6.0±1.9 in C, and 6.9±2.6 in D, p: 0.41). Significant increases in copeptin during tilt were observed in all Groups of VVS patients (A, B, C), including those with negative tilt (Group C: from 6.0±1.9 to 27.7±12.6pmol/l, p: 0.001), but not in controls. Following tilt termination, a greater increase was observed in copeptin values in Group B vs all other Groups A, C, and D (111.6±63.5 vs 29.5±51.3, 27.7±12.6, and 8.3±2.9, respectively)., Conclusions: Copeptin increases following tilt not only in VVS with a positive response, but also in typical history patients with a negative test. Increased copeptin levels following orthostasis may be useful for diagnosing VVS., (Copyright © 2017. Published by Elsevier B.V.)

We conducted a cross-sectional study to elucidate factors contributing to vasovagal reaction (VVR), the most frequent side effect following whole blood and apheresis donations. Complications recorded at the collection sites after voluntary donations by the Japanese Red Cross Tokyo Blood Center (JRC), in the 2006 and 2007 fiscal years, were analyzed by both univariate analysis and the multivariate conditional logistic regression model. Of 1,119,716 blood donations over the full two years, complications were recorded for 13,320 donations (1.18%), among which 67% were VVR. There were 4,303 VVR cases which had sufficient information and could be used for this study. For each VVR case, two sex- and age-matched controls (n = 8,606) were randomly selected from the donors without complications. Age, sex, body mass index (BMI), predonation blood pressure, pulse and blood test results, including total protein, albumin, and hemoglobin, were compared between the VVR group and the control group. In univariate analysis, the VVR group was significantly younger, with a lower BMI, higher blood pressure and higher blood protein and hemoglobin levels than the control group (p<0.001). Furthermore, blood protein and hemoglobin levels showed dose-dependent relationships with VVR incidences by the Cochran-Armitage trend test (p<0.01). For both sexes, after adjusting for confounders with the multivariate conditional logistic regression model, the higher than median groups for total protein (male: OR 1.97; 95%CI 1.76,-2.21; female: OR 2.29; 95%CI 2.05-2.56), albumin (male: 1.75; 1.55-1.96; female: 1.76; 1.57-1.97) and hemoglobin (male: 1.98; 1.76-2.22; female: 1.62; 1.45-1.81) had statistically significant higher risk of VVR compared to the lower than median groups. These elevated serum protein and hemoglobin levels might offer new indicators to help understand VVR occurrence.

Background: The diagnosis of vasovagal syncope continues to be difficult despite the use of accurate histories, tilt testing and implantable loop recorders. A circulating biomarker might be useful to facilitate diagnoses. Both endothelin-1 and vasopressin are increased during positive tilt tests resulting in syncope. Copeptin is a stable cleavage product of vasopressin formation. We conducted a pilot study to assess the utility of endothelin-1 and copeptin as circulating biomarkers of vasovagal syncope., Methods: Three populations were studied: syncope patients, epilepsy patients and controls. Vasovagal syncope diagnosis was ascertained with the Calgary Syncope Score and epilepsy diagnosis was confirmed with EEG. Plasma levels of endothelin-1 were measured using by ELISA and copeptin levels were determined using an EIA kit., Results: Asymptomatic control subjects had mean age 35 ± 11 years (7/22 male); epileptic subjects had mean age 32 ± 7 years (4/15 male); and syncope subjects had mean age 33 ± 16 years (4 of 21 male). Circulating plasma levels of endothelin-1 and copeptin were no different among the three groups. Mean concentrations of endothelin-1 were as follows: syncope, 23 ± 32 pg/mL; controls, 21 ± 17 pg/mL; and epileptics, 18 ± 12 pg/mL. Mean concentrations of copeptin were as follows: syncope, 1·29 ± 0·79 ng/mL; controls, 1·25 ± 0·79 ng/mL; and seizures, 1·23 ± 0·45 ng/mL. There were no significant correlations between syncope frequency and copeptin or endothelin-1 levels., Conclusion: Circulating plasma endothelin-1 and copeptin levels are not significantly different among populations of controls, syncope patients and seizure patients., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction and Objectives: Orthostatic intolerance (OI) syndromes are a confusing topic and determining a specific diagnosis to achieve optimal treatment can be troublesome. We sought to assess biomarker, hemodynamic and autonomic variables in OI patients (autonomic dysfunction [AD], postural orthostatic tachycardia syndrome [POTS] and neurally mediated syncope [NMS]) and healthy controls during supine and head-up tilt position in order to achieve a better diagnosis., Results: In response to head-up tilt, patients with AD presented a marked decrease in systolic blood pressure (SBP) (p=0.002), and a blunted increase in heart rate (HR) (p=0.04). Baroreceptor gain was almost absent in supine position and did not change in response to tilt. Patients with POTS had lower values of atrial natriuretic peptide (p=0.03) but similar neurohormonal biomarkers and hemodynamic and baroreceptor function in supine position compared to healthy subjects. However, in response to head-up tilting greater reductions in stroke volume (p=0.008) and baroreceptor gain (p=0.002) and greater rises in HR (p=0.001), total peripheral resistance (p=0.008), low frequency component of SBP variability (LF-SBP) (p=0.003) and plasma noradrenaline (p=0.03) were observed. Patients with NCS had similar biomarkers and autonomic indices to healthy subjects in supine position, but a larger decrease in baroreceptor gain (p=0.007) and a greater rise in LF-SBP (p=0.004) and plasma adrenaline (p=0.003) response to head-up tilting., Conclusion: Although different OI syndromes share similar symptoms, including blurred vision, syncope and dizziness particularly during orthostatism, they differ markedly regarding biochemical, autonomic and hemodynamic parameters. Assessment of these differences may be helpful for better diagnosis and management., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Objective: Neurocardiogenic syncope (NCS) is the most common cause of syncope in children and adolescents. Neurocardiogenic syncope occurs secondary to cerebral hypotension because of bradycardia, hypotension, or both. Head-up tilt-table test (HUTT) is the primary diagnostic test. Near-infrared spectroscopy (NIRS) is a noninvasive technology that directly monitors trends in regional tissue oxygen saturations over a specific body region. Placing an NIRS probe over the temporal region allows an indirect measurement of cerebral perfusion. Our hypothesis is that regional tissue oxygen saturation will decrease during an NCS episode and will remain stable in patients without syncope., Patients and Design: The investigators conducted a retrospective review of all HUTT utilizing cephalic NIRS performed at our institution from August 2012 to January 2013. Tests were classified as positive, negative, or psychogenic reactions. Paired t-test was used to determine statistical significance of NIRS changes and one-way analysis of variance was used to analyze baseline characteristics among the three groups., Results: Twelve patients were included in the study (female = 10). The average age was 14.4 years (range: 12-17). Five tests were positive for NCS, four were negative, and three demonstrated psychogenic reactions. Patients with a positive test had a sudden, significant decrease in regional tissue oxygen saturations (P = .009) by an average of 11.3 ± 5.2% compared with baseline. The decrease in regional tissue oxygen saturation preceded symptoms, hypotension, and bradycardia in all patients. Regional tissue oxygen saturation levels remained stable in patients with a negative test or psychogenic syncope., Conclusions: NIRS monitoring during HUTT produces a reliable, positive result that precedes clinical signs and symptoms. Further, it helps distinguish NCS from psychogenic syncope., (© 2014 Wiley Periodicals, Inc.)

Objective: To determine the clinical indications and adverse reactions of platelet apheresis procedure., Study Design: Cross-sectional, observational study., Place and Duration of Study: Blood Bank of Pakistan Atomic Energy Commission General Hospital, Islamabad, from January 2010 to December 2014., Methodology: Indications and adverse reaction verified for 200 consecutive platelet apheresis donations performed for 125 patients was included in this study. Data was analysed for descriptive variables using SPSS version 16., Results: Donor deferral rate in the study was 63.83%. All the donors were males (100%) and replacement donors. Most prevalent blood type was B-positive (n=63, 31.5%), followed by O-positive (n=59, 29.5%). Rh negative groups constituted 13.5% (n=27) of all the donors. Average age of platelet apheresis donors was 28.56 ± 5.77 years. Maximum numbers of donors were in age range 20 - 30 years. Average weight of the donors was 73.96 ± 11.96 kg. Mean pre-procedure platelet count of donors was 268,000/µL. The postprocedure average platelet count was approximately 200,000/µL. The mean duration of a platelet apheresis session was 78.27 ± 26.07 minutes. Average volume of the final product was 412.53 ± 45.33 ml. Average volume of anti-coagulant acid citrate dextrose used per procedure was 300 ± 40 ml, 245 ml returned to donor along with returned blood while 55 ml used as anticoagulant in final concentrate. Of total 200, two (1%) final products were contaminated with red cells. Three (1.5%) products were not issued and finally expired. Of the 125 patients for which plateletpheresis procedures were performed, 54 (43.2%) patients were males and 71 (56.8%) were females (M: F=0.76:1). Six donors (3%) had adverse events: three donors (1.5%) had mild reactions, two (1%) moderate reaction, and one donor (0.5%) developing hematoma. None had severe or life-threatening reactions., Conclusion: Plateletpheresis procedure is relatively safe and forms an important adjuvant to blood bank inventory.

Objectives: To explore the differences in erythrocyte hydrogen sulfide (H2S) production in children with vasovagal syncope (VVS)., Study Design: A total of 54 children including 27 with VVS, aged 6-16 years (mean age 11.3 ± 3.3 years), and 27 healthy children, aged 3-17 years (mean age 10.4 ± 1.8 years) were included in the study. Children with VVS had symptoms of dizziness, pallor, blurred vision, nausea, and some had syncope. Erythrocyte H2S production was measured by a sulphur-sensitive electrode. Flow-mediated dilation (FMD) of brachial artery was measured for each patient by vascular ultrasound., Results: H2S production from erythrocytes was significantly increased in the children with VVS compared with controls (P < .01). The erythrocytic H2S production in the VVS-vasoinhibitory subgroup was obviously higher than that in VVS-cardioinhibitory (P < .05) and VVS-mixed inhibitory subgroups (P < .05). FMD in the VVS-vasoinhibitory subgroup was greater than that in the VVS-cardioinhibitory (P < .05) and the VVS-mixed subgroups (P < .05). The erythrocytic H2S production had a positive linear correlation with FMD in children with VVS (P < .05)., Conclusions: Increased erythrocyte H2S production may be involved in the pathogenesis of VVS in children., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the clinical significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in the differentiation of patients with cardiac and reflex syncope., Methods: The study included a group of 100 patients (56 women, 44 men), aged 18-77 years (mean 52.6 ± 16.7), with a history of reflex (group I) or cardiac syncope (group II). Diagnosis of syncope was performed according to the European Society of Cardiology (ESC) guidelines. In all patients, the concentration of NT-proBNP was measured., Results: The assessment of NT-proBNP concentrations showed significantly higher concentrations in group II than in group I (448.7 ± 212.2 vs. 68.2 ± 64.1 pg/ml, P<0.0001). The receiver operating characteristic (ROC) curve analysis revealed that the concentration of NT-proBNP at 210.5 pg/ml may be a useful cut-off point which allows the prediction of cardiac syncope with 98 % specificity, 94 % sensitivity, and 94 % negative predictive value. In patients with cardiac arrhythmias and conduction abnormalities, the concentrations of NT-proBNP were higher in comparison to those without such disorders., Conclusions: The concentration of NT-proBNP is useful in the diagnosis of syncope and may initially guide the diagnostic process. The NT-proBNP value exceeding 200 pg/ml seems to be the most rational in determining cardiac syncope.

Syncope is a transient loss of consciousness, which is the result of global brain hypoperfusion, characterized by rapid onset, short duration, and spontaneous complete resolution. Syncope is a common clinical problem due to its complex, multi-causal etiology, not completely understood pathogenesis and potential complications. Diagnosis of syncope is often associated with the implementation of many medical tests. In the recent years, the role of determining the concentration of NT-proBNP in the differential diagnosis of syncope has been highlighted. Aims of the study was analysis of NT-proBNP concentrations in patients with cardiogenic syncope in comparison to patients with neurogenic syncope and determination of the threshold value of NT-proBNP to differentiate cardiac and neurogenic syncope and to determine its sensitivity and specificity. The study included 160 pts (64 man, 96 women), aged 18 - 77 yrs (mean age 50,6) with a reflex syncope (group I) or cardiac syncope (group II). To determine the etiology of syncope, collected were: medical history for symptoms and circumstances of the syncope, measurements of blood pressure, resting ECG recording, cardiac echocardiography, and the concentration of NT-proBNP levels. Results: the group I included 80 pts (29 men, 51 women), aged 18 - 72 yrs (mean age 41.2). Group II included 80 pts (35 man, 45 women), aged 38 - 77 yrs (mean age 62.1). The assessment of concentrations of NT-proBNP showed significantly higher levels in group II than group I (467.6 +/- 227.4 vs 64.1 +/- 59.1; p <0.0001). In patients with arrhythmias and conduction abnormalities, the levels of NT-proBNP were higher in comparison to those without such disorders (364 +/- 249 vs. 171 +/- 209 pg/ml, p < 0.001). It was found that the concentration of NT-proBNP at 230.6 pg/ml might be a cut-off point that allows the prediction of cardiogenic cause of syncope with 96% specificity, 92% sensitivity and 93% negative predictive value. Conclusions: 1. The concentration of peptide NT-proBNP patients with reflex syncope. 2. It was shown that the cut off concentration of the NT-proBNP equal 230.6 pg/ml is characterized by the high sensitivity, specificity, and negative predictive value in determining the etiology of syncope.

Objective: To explore the predictive value of serum iron in differentiating between vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children., Methods: Totally 57 children (aged 4-17 years, POTS 40 cases, and VVS 17 cases) who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2009 to September 2012 were included in the study. The diagnoses were analyzed by the value of serum iron and receiver operating characteristic (ROC) curves used to explore the predictive value of different serum iron in differential diagnosis between VVS and POTS., Results: There were significant differences in the median value of POTS [17.4 (interquartile range 13.5 -21.8) μmol/L] and VVS [8.9 (interquartile range 7.5-17.6) μmol/L] (P<0.01). When the value of serum iron was 11.8 μmol/L, the sensitivity and specificity of the differential diagnosis between VVS and POTS were 92.5% and 64.7%, respectively., Conclusion: The serum iron might be used as an initial diagnostic method in differential diagnosis between VVS and POTS, based on the history of the patients.

Background: Although automated cell separators have undergone a lot of technical refinements, attention has been focused on the quality of platelet concentrates than on donor safety. We planned this prospective study to look into donor safety aspect by studying adverse events in normal healthy plateletpheresis donors., Study Design and Methods: The study included 500 healthy, first-time (n=301) and repeat (n=199) plateletpheresis donors after informed consent. The plateletpheresis procedures were performed on Trima Accel (5.1 version, GAMBRO BCT) and Amicus (3.2 version FENWAL) cell separators. The adverse events during procedure were recorded and classified according to their nature. The pre and post procedure hematological and biochemical profiles of these donors were also assessed with the help of automated cell counter and analyser respectively., Results: A total of 18% (n=90) adverse events were recorded in 500 plateletpheresis donors, of which 9% of were hypocalcaemia in nature followed by hematoma (7.4%), vasovagal reaction (0.8%) and kit related adverse events in (0.8%). There was significant post procedure drop in Hb, Hct, platelet count of the donors (p<0.0001) whereas WBC count showed a statistically significant rise (p<0.0001). Divalent cations (iCa(+), TCa(+), TMg(+)) also showed a statistically significant decline after donation (p<0.0001). However there were no statistically significance difference between adverse events in Trima Accel (5.1 version, GAMBRO BCT) and Amicus (3.2 version FENWAL) cell separators., Conclusion: Donor reactions can adversely affect the voluntary donor recruitment strategies to increase the public awareness regarding constant need for blood and blood products. Commonly observed adverse events in plateletpheresis donors were hypocalcemia, hematoma formation and vasovagal reactions which can be prevented by pre-donation education of the donors and change of machine configuration. Nevertheless, more prospective studies on this aspect are required in order to establish guidelines for donor safety in apheresis and also to help in assessing donor suitability, especially given the present trend of double product apheresis collections., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aims: Adenosine is a possible mediator in vasovagal syncope (VVS) via the activation of its receptors. High expression of adenosine A2A receptors (A2AR) has been reported in VVS. The function of these over-expressed receptors in this population has never been evaluated., Methods and Results: We used Adonis, a specific-made antibody with A2AR agonist properties, to evaluate binding parameters (i.e. dissociation constant KD) and cAMP production (i.e. EC50) by peripheral blood mononuclear cells of 16 VVS patients. Eight healthy volunteers served as controls. A2AR expression was higher in patients than controls; mean: 11.5 ± 1.2 vs. 7.7 ± 0.8 AU, P = 0.04. Also, KD values were higher in patients than controls: 2.1 ± 0.02 × 10(-7) vs. 5 ± 1 × 10(-8) M, P < 0.01 In controls, KD values were lower than EC50 (5 ± 1.7 × 10(-8) vs. 2.8 ± 0.4 10(-7) M, P < 0.01), but in patients, KD values did not differ from EC50: 2. ± 0.2 × 10(-7) vs. 2.5 ± 0.4 × 10(-7) M, P > 0.05. However, four patients had lower EC50 (3.5 ± 0.3 × 10(-8) M) than KD (2.9 ± 1.2 × 10(-7) M; KD/EC50 = 9.6), suggesting the presence of spare receptors., Conclusion: The function of A2AR of patients with VVS was preserved since their stimulation by Adonis led to cAMP production with an EC50 comparable with those in controls. However, their affinity was lower than those of controls. Our results suggest that A2AR are implicated in the physiopathology of VVS.

Aims: Orthostatic stimuli are known to elicit changes in vasoactive peptide levels. The hypothesis of no difference in adrenomedullin and/or galanin levels in patients with recurrent vasovagal syncope and healthy controls was tested in a passive 35-min head-up tilt test (HUTT)., Methods: Twenty eight persons (14 patients and 14 healthy controls) were tested in a 35-min/60° head-up tilt test with telemetry monitoring. Three blood samples were evaluated for each person during the HUTT. Plasma levels of adrenomedullin and galanin were analysed by the Kruskal-Wallis test for all sampling periods. Vagal influence was indirectly assessed by the break index., Results: There were no significant differences between groups in median values for either adrenomedullin or galanin plasma levels (all 6 p-values were greater than 0.4). For adrenomedullin, no significant difference between groups was found. For galanin, the rate of change between the 1st and 2nd measurement was significantly greater for patients (P=0.04), regardless of HUTT result but between the 2(nd) and 3(rd) measurement it was insignificant (P=0.36). In the group of positive cases, the break index increased significantly (P=0.02)., Conclusion: We confirmed that there is a different galanin secretion pattern during orthostatic provocation in patients with recurrent vasovagal syncope than healthy individuals. For adrenomedullin, no significant difference was found. A significant increment of the break index confirmed increased vagal influence in the subgroup of positive cases.

Objective: To improve the pathophysiological understanding of cardioinhibitory and vasodepressor reflex syncope, by evaluating orthostatic effects on electrical and hemodynamic variables. To unravel the pathogeneses further, we studied these effects during both the passive head-up tilt test and the active standing test., Background: The current knowledge of the compromised autonomic balance in patients with reflex syncope is limited. The orthostatic responses to head-up tilt test in cardioinhibitory and vasodepressor patients differ, suggesting different pathogeneses; however, the more physiological active standing test represents daily life situations better., Methods: We included 74 patients; 36 cardioinhibitory and 38 vasodepressor. Patients were compared with respect to vascular hemodynamics and heart rate variability during the change from supine to upright position. Resting electrolytes, brain natriuretic peptide (BNP), pro-atrial natriuretic peptide (pro-ANP), and the C-terminal of pro-vasopressin, copeptin were measured., Results: Resting systolic blood pressure was higher in cardioinhibitory (117.8 ± 15.7 mmHg) than in vasodepressor patients (109.1 ± 15.3 mmHg, p < 0.001). Changes in heart rate tended to be smaller in cardioinhibitory patients (6.7 ± 9.8 vs. 10.7 ± 8.9 bpm, p = 0.056). Heart rate variability was lower and changed less in cardioinhibitory patients (p < 0.05). Cardioinhibitory patients had higher pro-ANP levels (63.5 ± 18.8 pM) compared to vasodepressor patients (54.2 ± 31.4 pM, p = 0.018). Responses during active standing were attenuated compared to head-up tilt in both groups., Conclusions: This study demonstrated that cardioinhibitory patients had higher blood pressure, attenuated hemodynamic responses, and reduced autonomic regulation compared to vasodepressor patients. Furthermore, cardioinhibitory patients showed a sympathetic predominance in their modulation of autonomic responses. Orthostatic responses induced by active standing were modest and did not sufficiently explain potential pathophysiological differences between cardioinhibitory and vasodepressor patients.

Objectives: The purpose of this study was to investigate the hypothesis that responses to the ATP test and head-up tilt test (HUT) may be correlated with different purinergic profiles., Design and Setting: The ATP and HUT identify distinct subsets of patients with neurally mediated syncope (NMS). Adenosine and its A(2A) receptors (A(2A)R) may be implicated in the pathophysiology of NMS in patients with positive HUT. Nothing is known about the purinergic profile of patients with positive ATP. PATIENTS AND MEASURES: This prospective study includes a consecutive series of patients with suspected NMS. All patients underwent both HUT and ATP. Before testing, samples were collected for measurement of baseline adenosine plasma level (APL) and expression., Results: A total of 46 patients (25 men and 21 women) with a mean age of 57±18 years were enrolled. The HUT test was positive in 27 patients and the ATP test in 20. Both tests were positive in 9 and negative in 8. High APL was associated with high probability of positive HUT while low APL was associated with high probability of positive ATP. Expression of A(2A)R was lower in patients with positive ATP than in those with positive HUT., Conclusion: These findings indicate that patients with NMS present different purinergic profiles and that responses to HUT and ATP are correlated with these profiles.

Objective: To explore the predictive value of plasma hydrogen sulfide (H(2)S) in differentiating between vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children., Study Design: Patients were divided between the POTS group (n=60) and VVS group (n=17) by using either the head-up test or head-up tilt test. Twenty-eight healthy children were selected for the control group. Plasma concentrations of H(2)S were determined for children in all groups (POTS, VVS, and control)., Results: Plasma levels of H(2)S were significantly higher in children with VVS (95.3±3.8 μmol/L) and POTS (100.9±2.1 μmol/L) than in children in the control group (82.6±6.5 μmol/L). Compared with the VVS group, the POTS group had plasma levels of H(2)S that were significantly increased. The receiver operating characteristic curve for the predictive value of H(2)S differentiation of VVS from POTS showed a H(2)S plasma level of 98 μmol/L as the cutoff value for high probability of distinction. Such a level produced both high sensitivity (90%) and specificity (80%) rates of correctly discriminating between patients with VVS and patients with POTS., Conclusion: H(2)S plasma level has both high sensitivity and specificity rates to predict the probability of correctly differentiating between patients with VVS and patients with POTS., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The pathophysiology of vasovagal syncope is poorly understood, and the treatment usually ineffective. Our clinical experience is that patients with vasovagal syncope fall into 2 groups, based on their supine systolic blood pressure, which is either normal (>100 mm Hg) or low (70-100 mm Hg). We investigated neural circulatory control in these 2 phenotypes., Methods and Results: Sympathetic nervous testing was at 3 levels: electric, measuring sympathetic nerve firing (microneurography); neurochemical, quantifying norepinephrine spillover to plasma; and cellular, with Western blot analysis of sympathetic nerve proteins. Testing was done during head-up tilt (HUT), simulating the gravitational stress of standing, in 18 healthy control subjects and 36 patients with vasovagal syncope, 15 with the low blood pressure phenotype and 21 with normal blood pressure. Microneurography and norepinephrine spillover increased significantly during HUT in healthy subjects. The microneurography response during HUT was normal in normal blood pressure and accentuated in low blood pressure phenotype (P=0.05). Norepinephrine spillover response was paradoxically subnormal during HUT in both patient groups (P=0.001), who thus exhibited disjunction between nerve firing and neurotransmitter release; this lowered norepinephrine availability, impairing the neural circulatory response. Subnormal norepinephrine spillover in low blood pressure phenotype was linked to low tyrosine hydroxylase (43.7% normal, P=0.001), rate-limiting in norepinephrine synthesis, and in normal blood pressure to increased levels of the norepinephrine transporter (135% normal, P=0.019), augmenting transmitter reuptake., Conclusions: Patients with recurrent vasovagal syncope, when phenotyped into 2 clinical groups based on their supine blood pressure, show unique sympathetic nervous system abnormalities. It is predicted that future therapy targeting the specific mechanisms identified in the present report should translate into more effective treatment.

Aims: Nitric oxide (NO) formed in the vascular endothelium produces, among other effects, a strong vasodilation. In order to evaluate the possible role of NO in hypotension induced by head-up tilt test (HUT), we measured plasma levels of its metabolites, nitrites and nitrates (NOx), during the test., Methods and Results: Twelve patients with vasovagal syncope and positive HUT [HUT(+)] (mean age: 23+/-5 years) and 13 healthy volunteers with negative HUT (controls) (mean age: 24+/-5 years) were included. Venous blood samples were obtained during the baseline stage for biochemical measurements. Plasma values of NOx were obtained under baseline conditions (T0), at the end of the HUT (T1), and 15 min after the end of the HUT (T2). The baseline biochemical values as well as haemodynamic parameters were similar in HUT(+) patients and controls. NOx plasma values (in micromol/L) were as follows [HUT(+) vs. controls]: T0: 5.7+/-1.6 vs. 8.8+/-4.7 (P=0.05), T1: 6.1+/-3.2 vs. 8.5+/-3.6 (P=NS), and T2: 6.1+/-3 vs. 10.2+/-8.9 (P=NS). The NOx levels were directly correlated with the insulin levels (Spearman's R=0.53, P=0.008)., Conclusion: Baseline plasma levels of NOx were significantly lower in HUT(+) patients than in controls. However, since the expected increase in NOx values during HUT-induced syncope was not observed, the possible role of NO in vasovagal hypotension is uncertain.

Objective: To investigate clinical features of childhood vasovagal syncope (VVS) and the possible relationship between changes of plasma and platelet 5-hydroxytryptamine (5-HT) and childhood VVS., Method: Forty-one children who were diagnosed as VVS because of positive head-up tilt test (HUTT) in Capital Institute of Pediatrics were enrolled as HUT-positive group, while 36 healthy children as control group. Clinical features of all children were analyzed, and blood samples of all children were obtained. Plasma and platelet 5-HT was measured by enzyme-linked immunosorbent assay (ELISA)., Result: (1) The mean age of 41 VVS children was (10.5 +/- 1.8) years, and there were more girls than boys with the boys to girls ratio of 1:1.4. (2) Presyncopal symptoms occurred in 33 patients (80.4%), among whom dizziness had a high rate: 78.8%. (3) Commonly, there were some provocation factors before syncope, among which long-time standing was the most common one with the rate of 91.7%. (4) The mean time of positive response in BHUT and SNHUT were (20.6 +/- 8.6) minutes and (5.0 +/- 2.2) minutes, respectively. Duration of syncope was shorter than 5 minutes. (5) HUTT positive response included vasodepressor type with the rate of 61.0%, cardioinhibitory type with 14.6%, and mixed type with 24.4%. (6) There were no significant differences in baseline heart rate, systolic blood pressure and diastolic blood pressure between VVS children and healthy children. And it was the same among different types of VVS children. (7) There were no significant differences in plasma 5-HT between VVS group of baseline or HUTT-positive and control group [(27.51 +/- 1.32) microg/L vs.(27.28 +/- 2.48)microg/L, t = 0.518, P = 0.606; (27.51 +/- 1.32) microg/L vs.(28.05 +/- 1.40) microg/L, t = 2.044, P = 0.167]. There were no significant differences in platelet 5-HT concentration between VVS group of baseline and control group [(82.30 +/- 6.06) 10(9) ng/L vs. (79.88 +/- 5.79) 10(9) ng/L, t = 1.788, P = 0.780].(8) HUTT-positive platelet 5-HT concentration of VVS children was significantly higher than baseline value [(97.90 +/- 6.59) 10(9) ng/L vs. (82.30 +/- 6.06) 10(9) ng/L, t = 11.26, P = 0.00]., Conclusion: There were no significant changes in plasma 5-HT in children with VVS during baseline, syncope or pre-syncope, which suggests that plasma 5-HT might not be valuable for the prediction of syncope trigger. However, platelet 5-HT of VVS children was obviously higher during syncope and presyncope, which suggests that central serotonergic system might be involved in the pathogenesis of VVS.

Objective: Vasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK., Methods: A random sample of 1,000 subjects aged 34-60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants' CK level. We prepared this report according to the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest., Results: The proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women., Interpretation: Low CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope.

Objective: Distinguishing epileptic generalized tonic-clonic seizures (GTCS) from either psychogenic nonepileptic seizures (PNES) or vasovagal syncope (VVS) is important. In this study, we investigated the use of postictal serum creatine phosphokinase (CPK) concentrations in distinguishing between these events., Methods: Patients admitted to the Neurology Ward at Namazi Hospital in Shiraz, Iran, with an attack of transient loss of consciousness and abnormal movements witnessed by a neurologist were studied. We categorized the patients into three groups: 20 patients with GTCS, 22 with VVS, and 20 with PNES. A group of 20 normal healthy individuals were included in the study as the control group. Serum CPK concentration was measured 12-15 h after the attack in all patients and at one time in the control group. A P value less than 5% was considered significant., Results: There were no significant differences between the four groups with respect to age and sex. Mean CPK concentrations statistically significantly differed between the four groups, with higher levels in patients with GTCS (P=0.0001). Serum CPK concentration had a sensitivity of 75% and specificity of 86% for the diagnosis of GTCS. CPK concentration was above 160 mg/dl in 75% of patients with GTCS, 15% of patients with PNES, 13.6% of patients with VVS, and 15% of the control group (P=0.0001). The PNES, VVS, and control groups did not statistically significantly differ with respect to CPK concentrations., Conclusion: In patients with a recent loss of consciousness and abnormal movements, serum CPK concentration is a useful, practical, and relatively accurate parameter to assist in the differentiation of epileptic seizures from either VVS or PNES.

Objective: The susceptibility to suffer neurally mediated syncope and loss of consciousness varies markedly. In addition to vasodilatation and bradycardia, hyperventilation precedes loss of consciousness. The resultant hypocapnia causes cerebral vasoconstriction and peripheral vasodilatation. We postulate that more pronounced cerebral and peripheral vascular responses to reductions in arterial CO(2) levels underlie greater susceptibility to neurally mediated syncope., Methods: We compared vascular responses to CO(2) among 31 patients with histories of recurrent neurally mediated syncope and low orthostatic tolerance and 14 age- and sex-matched control subjects with no history of syncope and normal orthostatic tolerance. Vascular responses to CO(2) were calculated after all subjects had fully recovered and their blood pressures and heart rates were stable. We measured blood flow velocity in the middle cerebral artery (transcranial Doppler) and in the left brachial artery (brachial Doppler), and end-tidal CO(2) during voluntary hyperventilation and hypoventilation (end-tidal CO(2) from 21-45mm Hg), and determined the slopes of the relations., Results: Hypocapnia produced a significantly greater reduction in cerebral blood flow velocity and in forearm vascular resistance in patients with neurally mediated syncope than in control subjects. Opposite changes occurred in response to hypercapnia. In all subjects, the changes in cerebral blood flow velocity and forearm vasodilatation were inversely related with orthostatic tolerance., Interpretation: Susceptibility to neurally mediated syncope can be explained, at least in part, by enhanced cerebral vasoconstriction and peripheral vasodilatation in response to hypocapnia. This may have therapeutic implications.

Basic autonomic nervous function was evaluated in patients with neurocardiogenic syncope (NCS). Atropine, isoproterenol, propranolol, phenylephrine, and phentolamine were administered successively, and parasympathetic nerve activity and beta- (and alpha-) activity, sensitivity, and secretion of the sympathetic nerve were determined in patients with NCS and control subjects. In patients with NCS, beta- and alpha- sensitivity were higher and beta-activity and beta- and alpha-secretion lower than in control subjects. In patients with NCS, the increased basic beta-sensitivity may contribute to induce strong cardiac contractions and augment ventricular mechanoreceptor response, and a compensatory state against diminished neuronal sympathetic activity is suggested by the increased alpha-sensitivity.

In patients with neurocardiogenic syncope, the beneficial effects of increased daily fluid intake, without an accompanying high dose of salt, are unknown. Our aim was to (1) determine whether plasma volume was low in patients with recurrent neurocardiogenic syncope, and (2) determine how recommendation about increased daily fluid intake, without an accompanying high dose of sodium, effects plasma volume and if this potential therapy improves orthostatic tolerance. Eighty-six patients with neurocardiogenic syncope were recruited in a prospective randomized open study. After an initial head-up tilt test, patients were randomly assigned to either the hydration supplementation group (1500 ml of water + 1500 mg of NaCl/day) or the no treatment (control) group. After ten days a second head-up tilt test was performed. Plasma volume, osmolality, and total body water were measured at baseline, and heart rate, arterial blood pressure, and cardiac transthoracic impedance were monitored during tilting. Hydration treatment did not affect the number of positive tilt tests (52% initial day, 54% after treatment, NS). In both groups, the overall number of positive tilt tests decreased between the initial and final head-up tilt test. There was no association between low plasma volume and positive tilt test. Patients with the lowest plasma volume were equally distributed in both positive and negative tilt response groups. An increased daily intake of fluid, without an accompanying high dose of salt, had no measurable beneficial effect on tolerance to head-up tilting in patients with neurocardiogenic syncope. Moreover in this patient group there was no association between a low plasma volume and a reduced tolerance to orthostatic stress.

In patients with neurocardiogenic syncope, head-up tilt often evokes acute loss of consciousness accompanied by vasodilatation, increased plasma adrenaline and systemic hypotension. Since hypotension increases adrenaline levels and adrenaline can produce skeletal muscle vasodilatation by activating beta2 receptors, adrenaline might induce a positive feedback loop precipitating circulatory collapse. We hypothesized that propranolol, a non-selective beta-blocker, would prevent adrenaline-induced vasodilatation and thereby prevent syncope. Eight subjects with recurrent neurocardiogenic syncope and previously documented tilt-induced syncope with elevated plasma adrenaline levels participated in the present study. Subjects underwent tilt table testing after receiving oral propranolol or placebo in a double-blind randomized crossover fashion. Haemodynamic and neurochemical variables were measured using intra-arterial monitoring, impedance cardiography, arterial blood sampling and tracer kinetics of simultaneously infused [3H]noradrenaline and [3H]adrenaline. The occurrence of tilt-induced neurally mediated hypotension and syncope, duration of tilt tolerance, extent of the decrease in SVRI (systemic vascular resistance index) and magnitude of plasma adrenaline increases did not differ between the propranolol and placebo treatment phases. SVRI was inversely associated with fractional increase in plasma adrenaline during both phases. One subject did not faint when on propranolol; this subject's response is discussed in the context of central effects of propranolol. In this small, but tightly controlled, study, propranolol did not prevent tilt-induced vasodilatation, syncope or elevated plasma adrenaline.

Objectives: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF)., Patients and Methods: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation., Results: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients., Conclusions: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

Aims: To determine whether central serotoninergic system activity is impaired by orthostatic challenge in patients with neurocardiogenic syncope (NCS)., Methods and Results: Thirty-five [mean age: 24 (SD): 6 years] patients with a clinical history of NCS and positive head-up tilt test and 35 age-matched healthy volunteers (CON = 25+/-5 years) with negative response were studied. Overnight dexamethasone suppression test (DST) (1.5 mg given at 11 p.m.) was performed to assess the sensitivity of the hypothalamic-pituitary-adrenal axis by measuring next day cortisol (microg/dL) at 8 a.m. and 4 p.m. Cardiac autonomic function, cortisol, and prolactin (ng/dL) were also determined at baseline supine (BAS) and after 5, 10, and 15 min of orthostatic stress (OS) at 60 degrees . No significant differences were observed in cortisol plasma levels after the DST: CON = 0.6+/-0.6 microg/dL vs. NCS = 0.6+/-0.5; P = 0.7. Cardiac autonomic function, cortisol, and prolactin responses were similar in both study groups (CON vs. NCS; P > 0.05) during BAS: cortisol = 8.6+/-4 vs.8.7+/-4 microg/dL and prolactin = 16.8+/-9 vs. 16.8+/-9 ng/dL; OS-5: cortisol = 8.7+/-5 vs. 8.5+/-4 microg/dL and prolactin = 16.9+/-9 vs. 15.8+/-9 ng/dL; OS-10: cortisol = 8.5+/-5 vs. 8.1+/-3 microg/dL; prolactin = 16.2+/-9 vs. 15.8+/-9 ng/dL, and OS-15: cortisol = 9.0+/-5 vs. 8.4+/-4 microg/dL; prolactin = 17.1+/-9 vs. 15.5+/-9 ng/dL., Conclusion: Central serotoninergic response during orthostatic challenge was not impaired in patients with recurrent NCS. These findings suggest that the activation of the hypothalamic-pituitary-adrenal axis is not altered in patients with recurrent NCS.

Objective: To evaluate the role of peripheral serotoninergic system in the pathogenesis of vasovagal syncope., Background: Increased central serotoninergic activity was suggested to play a role in sudden inhibition of sympathetic activity responsible for the genesis of vasovagal syncope. There is good correlation between the central serotoninergic activity and the plasma levels of serotonine., Methods: In twenty-two patients (mean age 48 +/- 19 years, 10 men, 12 women) with suspected vasovagal syncope head-up tilt test (HUT) was performed. Passive HUT (60 degrees, 20 minutes) was followed, if negative, by nitroglycerine stimulated HUT (400 microg sublingually, 15 minutes). Blood samples were obtained at baseline (in supine position), in 5 minute, 15 minute of HUT and finally at syncope or end of the test. Plasma levels of serotonine were measured by enzyme-immunoassay (EIA) method., Results: HUT was positive in fifteen patients and negative in seven patients. In all HUT positive patients syncope developed after nitroglycerine stimulation. Mean duration of nitroglycerine phase was 4.8 +/- 1.2 min. In 5 min of HUT serotonine level was significantly lower in HUT positive patients HUT (102.40 +/- 43.11 vs 160.85 +/- 43.71 ng/ml, p = 0.01). At the time of syncope no significant differences were observed between HUT positive and HUT negative patients (184.26 +/- 118.72 vs 196.57 +/- 88.91 ng/ml, p = 0.40)., Conclusion: In patients with vasovagal syncope lower level of plasma serotonine were observed during early HUT when compared to controls. No differences in serotonin activity were observed at the time of syncope (Tab. 1, Fig. 1, Ref. 24).

Unlabelled: The stimulation of renin-angiotensin-aldosterone (RAA) system during tilt table test is caused by sympathetic nervous system activation by orthostatic stress and a serotonin release as well. In healthy individuals increase of plasma renin activity during test with maximal values on the peak of the test was described., Objective: The aim of the study was to assess the activation of RAAS in patients with neurally mediated syncope during the tilt table test by means of plasma renin activity and serum aldosterone levels., Material and Methods: The study was carried out in 31 patients aged 39.4 +/- 15.0 years (18 women and 13 men) with neurally mediated syncope during tilt test. Plasma renin activity was assessed in the baseline conditions, immediately after the test and 10 minutes after the test using radioenzymatic assay. Aldosterone concentrations were measured radioimmunologically, twice: after 30 minutes supine rest and after the syncope., Results: Plasma renin activity during supine rest was 2.2 +/- 2.4 ng/ml/h, rose after the syncope 2.5-fold to 5.2 +/- 4.5 ng/ml/h (p < 0.001 comparing to baseline) stayed on similar level approximately for the next 10 minutes--4.9 +/- 5.5 ng/ml/h (p = n.s.). In 11 patients (35%) 10 minutes after the test even further increase of PRA was observed. Serum aldosterone level increased significantly immediately after tilt test (90.0 +/- 72.9 vs 178.8 +/- 150.1 pg/ml, p < 0.01)., Conclusion: Authors showed, that in patients with NMS plasma renin activity increases and this increase lasts for 10 minutes after the syncope and the concentration of aldosterone increases immediately after tilt test.

Aims: Vasovagal syncope appears related to transient changes in sympathetic neural outflow. Several studies have documented sympathetic inhibition at the time of syncope. However, data on the activity of the sympathetic nervous system a short time before the onset of syncope are controversial. The aim of the study was to examine sympathoadrenal activity by measuring levels of plasma catecholamines and plasma cAMP in patients with vasovagal syncope induced in the head-up tilt test (HUT)., Methods and Results: Sixty-one syncopal patients (age 35 +/- 15 years) underwent the passive HUT (60 degrees, 45 minutes). Blood samples for measurement of noradrenaline (NA), adrenaline (A) and dopamine (D) were obtained prior to tilt (0 minutes), at 5 minutes of tilt and at syncope or at the end of the HUT (45 minutes). Two samples were obtained for measurement of cAMP: at 0 minutes and at the end of the test. Plasma levels of NA, A and D were measured using high-performance liquid chromatography; plasma cAMP was measured using a radioimmunoassay technique. Thirty-three patients (15 men, age 35 +/- 16 years) developed vasovagal syncope during the test (HUT-positive); twenty-eight patients (15 men, age 34 +/- 14 years) completed the test without syncope (HUT-negative). No significant differences in NA, A and D were observed between the two groups at baseline or at 5 minutes of tilt. At the time of syncope, catecholamine levels in HUT-positive patients were higher than baseline levels (NA 428 vs. 209 pg/ml, A 90 vs. 55 pg/ml, D 297 vs. 142 pg/ml) and higher than in HUT-negative patients (NA 428 vs. 263 pg/ml, A 98 vs. 67 pg/ml, D 297 vs. 195 pg/ml). cAMP levels increased at syncope and were higher than in non-syncopal patients at the end of the HUT (607 +/- 460 vs. 328 +/- 297 nmol/ml)., Conclusion: Vasovagal syncope induced by tilt testing is associated with increased levels of noradrenaline, adrenaline, dopamine and cAMP. These results suggest that sympathoadrenal activation antecedes development of vasovagal syncope and may play a role in its pathophysiology.