Pathogenesis Of Postural Tachycardia Syndrome Research Articles

Adrenergic Autoantibody-Induced Postural Tachycardia Syndrome in Rabbits.

BackgroundPrevious studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits.Methods and ResultsEight New Zealand white rabbits were coimmunized with peptides from the α1‐adrenergic receptor and β1‐adrenergic receptor (β1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope‐mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the β‐adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of β1AR antibodies. In contrast, the blood pressure response to infusion of the α1‐adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1‐adrenergic receptor antibodies. Injections of antibody‐neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays.ConclusionsThe differential allosteric effect of α1‐adrenergic receptor and β1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.

Plasma Homocysteine Level in Children With Postural Tachycardia Syndrome.

The study was designed to evaluate the changes of plasma homocysteine (Hcy) level in children with postural tachycardia syndrome (POTS) and explore its significance. A total of 65 subjects were recruited in our study, of whom 35 children were in the POTS group and 30 healthy children were in the control group. Plasma Hcy levels were determined in all subjects. The relationship between the plasma Hcy level and the symptom score was analyzed in the 35 POTS patients. The relationship between the plasma Hcy level and the change in heart rate from the supine to upright position (ΔHR) and between the plasma Hcy level and the rate of increase in heart rate from the supine to upright position (ΔHR/sHR × 100%) were analyzed in all subjects. The plasma Hcy levels were significantly higher in the children with POTS than those in the control group (9.78 [7.68, 15.31] μmol/L vs. 7.79 [7.46, 9.63] μmol/L, P < 0.05). The plasma Hcy levels were positively correlated with symptom scores in the POTS patients (n = 35, r = 0.522, P < 0.01). The plasma Hcy levels were also positively correlated with ΔHR (n = 65, r = 0.332, P < 0.01) and ΔHR/sHR × 100% (n = 65, r = 0.341, P < 0.01) in all the subjects. In conclusion, the plasma Hcy levels were elevated in the children with POTS positively correlated with the severity of POTS, suggesting that Hcy might be involved in the pathogenesis of POTS.

Increased Endogenous Sulfur Dioxide Involved in the Pathogenesis of Postural Tachycardia Syndrome in Children: A Case-Control Study.

Background:The pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO2) in patients with POTS.Methods:The study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SO2 was determined.Results:The plasma SO2 was significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SO2 levels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO2 (r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SO2 levels in all participants (r = −0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO2 (r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928–1.000), and the cutoff value of plasma SO2 level >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.Conclusions:Increased endogenous SO2 levels might be involved in the pathogenesis of POTS.

Serum Resistin Negatively Correlates with Clinical Severity of Postural Tachycardia Syndrome in Children.

This study was designed to analyse the serum resistin level in children with postural tachycardia syndrome (POTS) and its clinical significance. Twenty-one children with POTS and 31 healthy children as controls participated in the study. Clinical characteristics, heart rate and blood pressure in the supine and upright positions were monitored and collected during an upright test, and the symptom scoring of POTS patients was recorded. The serum resistin levels of patients in both groups were determined by enzyme-linked immunosorbent assay. The change in serum resistin levels in the POTS group before and after standing, as well as its correlation with symptom scores and change in heart rate after standing, was analysed. Compared with the control group, the serum resistin levels in the POTS group were significantly increased (P<0.01). The serum resistin levels in the POTS group before and after standing did not differ (P>0.05). There was a negative correlation between the serum resistin levels and a change in heart rate from the supine to upright position (correlation coefficient=-0.615, P<0.01). Moreover, serum resistin levels were negatively correlated with symptom scores (correlation coefficient=-0.493, P<0.05). Serum resistin levels in children with POTS were significantly higher than those in healthy children and negatively correlated with a change in heart rate from the supine to upright position and symptom scores. These results suggest a protective role of increased resistin in the pathogenesis of POTS.

Pathogenesis and Individualized Treatment for Postural Tachycardia Syndrome in Children.

Objective:Postural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children.Data Sources:The data analyzed in this review are mainly from articles included in PubMed and EMBASE.Study Selection:The original articles and critical reviews about POTS were selected for this review.Results:Studies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted.Conclusions:The pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.

Relationship between 24-hour urinary sodium and renin-angiotensin-aldosterone system in children with postural tachycardia syndrome

To analyze the relationship between 24 hours urinary sodium and renin-angiotensin-aldosterone system (RAAS) in children with postural tachycardia syndrome (POTS) and to explore low blood volume related pathogenesis of POTS. A total of 39 POTS children who were at the clinic or admitted to the Department of Pediatrics, Peking University First Hospital from June 2012 to February 2013 and 21 healthy children (control group) were enrolled, level of RAAS in plasma, 24-hour urinary sodium and plasma sodium were detected, respectively. Baseline data, levels of RAAS and hemodynamic parameters were compared between POTS and control group, as well as groups with different 24-hour urinary sodium levels of POTS. The angiotensin II levels of POTS children were significantly higher than that of control group ((105 ± 50) vs (84 ± 28) ng/L, P = 0.041), while no statistical significance was found in plasma renin and aldosterone (P > 0.05). Pearson correlation analysis showed that 24-hour urinary sodium and angiotensin II in children with POTS was negatively correlated (r = -0.536, P < 0.001). Angiotensin II, symptom score, upright heart rate and changes of heart rate were significantly higher in urinary sodium < 124 mmol/24 h group than that in urinary sodium ≥ 124 mmol/24 h group (P < 0.05). The regulating function disorder of RAAS may involve in the pathogenesis of POTS and cause sustained low blood volume in patients with POTS.

Changes of plasma intermedin during head-up tilt test in children with postural tachycardia syndrome and its significance

To explore possible mechanisms of postural tachycardia syndrome (POTS) by comparing plasma intermedin (IMD) during head-up tilt test (HUTT) in children with POTS. The study subjects were divided into two groups: POTS group and control group. The POTS group consisted of twenty-nine children (male 14, female 15) with POTS, the mean age (12.4 ±3.1) years old, admitted into Peking University First Hospital from November 2013 to June 2014. The control group consisted of 32 healthy children (male 17, female 15). Their mean age was (11.6±2.2) years old, who were confirmed as healthy by physical examination and HUTT. Finapres Medical System was used to continuously monitor heart rate and blood pressure during HUTT, and electrocadiogram was performed. Supine systolic and diastolic blood pressure, mean arterial pressure (MAP), ΔMAP (standing mean arterial pressure-supine MAP), supine heart rate and ΔHR (standing HR-supine HR) were compared between POTS group and control group. Sandwich immunoluminescence assay was used to test plasma IMD. The plasma IMD level was compared in supine between POTS and control group. The plasma IMD level in supine was compared with HUTT in POTS group. No significant differences were found in age, height, weight, supine systolic and diastolic blood pressure, MAP, ΔMAP and supine heart rate between POTS group and control group (P>0.05). ΔHR in POTS group was significantly higher than that of control group ((48±10) vs. (22±7) beats /min, t=9.797, P<0.05). The plasma IMD level in POTS group was lower than that of control group in supine position ((497±61)×10(-6) vs. (529±58)×10(-6) mg/L, t=2.117, P<0.05). But, it was higher during HUTT than supine IMD in POTS group ((537±57) ×10(-6) vs. (497±61)×10(-6) mg/L, t=-2.464, P<0.05). The plasma delta IMD level (HUTT vs. supine) was positively correlated with delta HR in POTS group (r=0.435, P<0.05). The excessively high heart rate during HUTT have a positive correlation with plasma IMD, which may play a role in the pathogenesis of POTS in children.

Total Peripheral Vascular Resistance, Cardiac Output, and Plasma C-Type Natriuretic Peptide Level in Children with Postural Tachycardia Syndrome

To investigate the total peripheral vascular resistance (TPVR), cardiac output (CO), and plasma C-type natriuretic peptide (CNP) levels in children with postural tachycardia syndrome (POTS) during supine, upright, and return to supine. Twenty-nine children with POTS, aged 12 ± 3 years, were recruited, and 32 healthy children, aged 11 ± 2 years, served as controls. Heart rate (HR), blood pressure, TPVR, and CO were continuously monitored with Finapres Medical System, and plasma CNP levels were detected with Sandwich immunoluminescence assay. In children with POTS, upright TPVR and CO were significantly lower than those in supine position, and they rose again when they returned to supine position. However, in healthy control patients, both TPVR and CO did not change during supine, upright, and supine again positions. Also, in the supine position, there was no significant difference in TPVR and CO between POTS children and control subjects (P > .05). When upright, however, TPVR and CO in children with POTS were significantly lower than those of controls. Plasma CNP levels were significantly greater in children with POTS than that of controls (32.8 ± 9.7 vs 24.2 ± 8.4 [pg/mL], P < .01), and symptom scores and ΔHR positively correlated with plasma CNP levels in children with POTS (symptom scores: r = 0.490, P < .01; ΔHR: r = 0.508, P < .001), but CO negatively correlated with plasma CNP levels (r = -0.446, P < .01). Reduced TPVR and CO associated with the elevated plasma CNP might be involved in the pathogenesis of POTS.

Familial orthostatic tachycardia

Postural tachycardia syndrome is an autonomic disorder primarily of younger women. The patient population is heterogeneous, making diagnosis and treatment a challenge. A mutation in the norepinephrine (noradrenaline) transporter gene prompted further genetic analysis. Eleven new mutations were found in the human norepinephrine transporter gene, although none were directly associated with postural tachycardia syndrome. The 5'-flanking -1012C --> T variant of the dopamine beta-hydroxylase gene was slightly increased and protection was associated with a reduced incidence of two mutations in the endothelial nitric oxide synthase gene, and one in endothelin-1. Mutations in other disease-related genes suggest a potential relationship with the pathogenesis of postural tachycardia syndrome. Benign joint hypermobility syndrome, for example, shares similar autonomic symptoms and is linked to a mutation in tenascin-X. Additional genetic findings are discussed as potential contributors to vascular health and neurodegeneration. Genetic testing can reveal molecular mechanisms of disease and provide an additional strategy for diagnosis and treatment of heterogeneous patient populations such as postural tachycardia syndrome. It is quite likely that the pathogenesis of this disorder will be attributed to numerous genetic mutations, both subtle and overt. Therefore, continued study of the relationships between genotype and phenotype are necessary to better understand this syndrome and others with associated dysautonomia.