Previous studies suggest that the beta2-adrenoceptor functions abnormally in patients with postural tachycardia syndrome (POTS) and may contribute to their altered hemodynamic profile. To test the hypothesis that the beta2-adrenoceptor response is decreased in POTS, we studied: (1) the arterial vasodilation response to the beta agonist, isoproterenol, and (2) the distribution of common polymorphisms (codons 16 and 27) of the gene coding the receptor (beta2-AR) in a large population with POTS. We measured plasma catecholamines and monitored hemodynamics and changes in forearm and leg blood flow to incremental doses of intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy subjects. For polymorphism assessment we collected DNA from 57 patients with POTS and compared with 67 age-sex matched healthy subjects. Circulating catecholamines were significantly higher in POTS subjects compared with controls. Intrabrachial and intrafemoral isoproterenol infusion elicited a dose-dependent increase in blood flow. In healthy subjects, blood flow increased (mean+/-SEM) 400+/-70% in the forearm and 170+/-40% in the leg, but only 280+/-60% in forearms and 120+/-20% in legs of patients with POTS (ANOVA for both P<0.001). The genotype and allele distributions for codons 16 and 27 beta2-AR variants were not different in the 2 groups. However, the blood pressure and plasma norepinephrine levels diverged in patients according to their genotype. Patients with Gly16Gly and patients with Glu27Glu had lower plasma catecholamines and higher supine and upright blood pressure, compared with other genotypes. Therefore, both decreased beta2-adrenoceptor-related vasodilation and beta2-AR polymorphisms may contribute to the hemodynamic diversity of patients with POTS.

This study analyses the changes in cerebral blood flow (CBF) velocity occurring in the near syncopal phase of head-up tilt test (HUT) to determine whether their appearance during the premonitory symptoms permits the differentiation of the different types of haemodynamic response. Six hundred and nineteen patients aged 35.9 +/- 16.4 with a prior history of syncope (55%) or presyncope (45%) were studied. Head-up tilt test was positive in 585 patients. The test was interrupted before syncope, once hypotension was evident and CBF changed. A vasovagal reaction (VVR) was observed in 245 patients. They had a 59% fall in diastolic CBF velocity, whereas systolic CBF velocity decreased by 12%. Postural orthostatic tachycardia syndrome (POTS) was observed in 82, systolic and diastolic CBF velocity decreased 44 and 60%, respectively. A similar response was observed in 258 patients with the orthostatic intolerance (OI) pattern. No significant changes were observed in the negative group. Patients with VVR had changes in CBF velocity, which are different from those presented by patients with POTS and OI pattern. Cerebral blood flow monitoring is useful to increase the yield of HUT and may allow early interruption before syncope occurs, reducing patient discomfort.

Postural tachycardia syndrome (POTS), characterized by orthostatic tachycardia in the absence of orthostatic hypotension, has been the focus of increasing clinical interest over the last 15 years 1. Patients with POTS complain of symptoms of tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache and mental clouding. Patients with POTS demonstrate a heart rate increase of >or=30 bpm with prolonged standing (5-30 minutes), often have high levels of upright plasma norepinephrine (reflecting sympathetic nervous system activation), and many patients have a low blood volume. POTS can be associated with a high degree of functional disability. Therapies aimed at correcting the hypovolemia and the autonomic imbalance may help relieve the severity of the symptoms. This review outlines the present understanding of the pathophysiology, diagnosis, and management of POTS.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, relatively common autonomic disorder typically affecting younger females. It is distinguished by a dramatic increase in heart rate on the assumption of an upright posture from the supine position. The authors provide an overview of the demographics, clinical assessment, diagnostic features, differential diagnoses, pathogeneses and medical treatment of patients with POTS, with an emphasis on the clinical treatment of the dental patient affected by the syndrome. Patients frequently exhibit symptoms of lightheadedness, fatigue, palpitations and syncope. Patients with POTS may have Ehlers-Danlos syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the Brugada syndrome. Despite widespread dissemination of information regarding POTS in the medical literature, scant information on it has appeared in dental publications. Dentists need to be familiar with the clinical features of POTS and be prepared to treat patients at risk of developing syncope.

To examine the association between migraine and syncope-related autonomic nervous system (ANS) symptoms. A population-based study among migraineurs with and without aura (n = 323) and control subjects (n = 153) was conducted. A systematic questionnaire and cardiovascular measurements during rest, while standing, and after venipuncture addressed the prevalence of syncope, orthostatic intolerance, orthostatic hypotension (OH), and the postural tachycardia syndrome (POTS) in migraineurs and control subjects. The lifetime prevalence of syncope in all participants was 41%, more often in women (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p < 0.001). There was no association between ANS symptoms and the severity of migraine or migraine subtype. Cardiovascular measurements and the prevalence of POTS and OH did not differ significantly between migraineurs and control subjects. This population-based study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction.

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.

Complex regional pain syndromes (CRPS) involve neuropathic limb pain and localized circulatory abnormalities. The authors hypothesized that (1) pediatric CRPS patients exhibit systemic autonomic symptoms and orthostatic and/or cardiac sympatho-vagal dysregulation and (2) their orthostatic regulation differs from healthy controls and pediatric patients with postural orthostatic tachycardia syndrome (POTS). CRPS children and adolescents (n=20) underwent a 6-week trial of physical therapy and cognitive-behavioral treatment. Measures included pain and function scores, regional and systemic autonomic symptom profiles, heart rate and blood pressure with tilt, heart rate variability indices, and baroreflex gain. Systemic autonomic symptoms were recorded in 55 healthy pediatric controls. Tilt responses in CRPS patients were compared with those of 21 POTS patients and 39 healthy controls. CRPS patients' regional autonomic symptoms, pain, and limb function improved over 6 weeks (P<0.01). At baseline CRPS patients reported more systemic autonomic symptoms than controls (P<0.05). Tilt table test showed orthostatic stability, but the mean heart rate increase with tilt was greater in CRPS patients than controls (P<0.001). POTS patients showed significant increases with tilt in mean heart rate and diastolic and systolic blood pressures compared with controls (P<0.001). There were significant increases in the mean systolic and diastolic blood pressures in POTS compared with CRPS patients but no difference in the mean heart rate between groups. CRPS patients reported multiple regional and systemic autonomic symptoms that improved during the study course, and they experienced minimal and transient tilt table-induced hemodynamic changes compared with POTS patients but relatively similar to controls.

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). 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. 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. 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.

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients. Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic 'co-morbidity' perhaps underlies the clinical concordance. Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).

Postural orthostatic tachycardia syndrome encompasses a group of disorders characterized by orthostatic intolerance. We describe the anaesthetic management of analgesia for labour and of Caesarean section in a parturient suffering from this disorder. Worsening of her symptoms during pregnancy was managed with an increase in the dose of beta-blockers taken by the patient. Epidural analgesia was instigated early to attenuate the stress of labour and avoid consequent triggering of a tachycardic response. Slow titration of epidural analgesia and anaesthesia after an adequate fluid preload was undertaken to minimize hypotension and subsequent tachycardia. Neuraxial opioid, combined with non-steroidal anti-inflammatory drugs and bilateral iliohypogastric and ilioinguinal nerve blocks were used to optimize postoperative analgesia.

Pyridostigmine has been proposed for the treatment of postural orthostatic tachycardia syndrome in adults at a dose of 60 mg twice daily, but no dosing recommendation exists for children. With the approval of our local ethics board, we tested the pharmacokinetics of pyridostigmine in 6 children with myasthenia and a pediatric index patient with severe postural orthostatic tachycardia syndrome whose condition failed all conventional therapy and who had developed significant postural hypertension. Pyridostigmine was quantified by using a validated, semiautomated, and specific high-performance liquid chromatography/tandem mass spectrometry assay in combination with online column-switching extraction and turbo electrospray ionization. The patient with postural orthostatic tachycardia syndrome showed a dose-dependent favorable response to oral pyridostigmine. Pharmacokinetic evaluation revealed a short half-life of 2.29 hours, similar to the 2.0 +/- 0.63 hours in the patients with myasthenia. The patient with postural orthostatic tachycardia syndrome has subsequently been treated at a dose of 45 mg in the morning, 30 mg at lunchtime, and 15 mg at bedtime; after 9 months, there has been persistent positive effect and without additional blood pressure medication. No major adverse effects occurred. Pyridostigmine has been a safe and effective treatment modality for this child with postural orthostatic tachycardia syndrome. The short half-life suggests that dosing 3 times per day is preferable.

Tilt table testing represents a valuable diagnostic method in suspected neurally mediated syncope. As sympathovagal imbalance and impaired baroreceptor sensitivity (BRS) have been observed in these patients, both methods were used in this study to investigate whether a combination of these parameters would improve sensitivity and whether specific patterns of neurally mediated syncopes would correspond to characteristic trends in heart rate variability (HRV) and BRS. Fifty-one pts. (29 female, mean age 14.5 +/- 3.9 y) with unexplained syncope and 15 control subjects (9 female, mean age 14.8 +/- 3.0 y) were tested following a standard tilt table test protocol. Power spectral analysis (PSA) of HRV and BRS calculation were used additionally to beat-to-beat blood pressure and ECG-monitoring. Twenty-three out of 51 pts. (45%) experienced a syncope after 18 +/- 10.2 min of tilting. In 2/23 patients (8.6%) a postural tachycardia syndrome (POTS), in 14/23 (60.8%) a neurally mediated syncope of mixed type, in 2/23 (8.6%) a vasodepressor syncope and in 5/23 (21.7%) a cardioinhibitory syncope with asystole were observed. PSA of HRV and BRS revealed a specificity, sensitivity, and positive and negative predictive values of the cut-off points in combination (LF/HF > or = 2.7 and BRS > or = 8) of 93.3%, 65.2%, 93% and 39%, respectively. In this study population, BRS and PSA of HRV were able to improve sensitivity of tilt testing after unexplained syncope. Specific BRS or HRV patterns in different mechanisms of neurally mediated syncope could not be identified possibly due to the small sample size.

We assessed the potency of octreotide and midodrine, and their combination, in the treatment of the postural tachycardia syndrome (POTS) and orthostatic intolerance (OI). Nine patients with POTS and six patients with OI stood for up to 1 hour while their HR and BP were monitored. Patients received on separate days, midodrine 10 mg 1 hour before testing, octreotide 0.9 micro g/kg 8 minutes before testing or combination therapy. Standing time in the patients with POTS was 41.2 +/- 8.4 minutes and not improved by midodrine or octreotide, but increased to 56.3 +/- 2.7 (P < 0.01) minutes following combination therapy. The standing heart rate in POTS, 114 +/- 0.7 bpm, was suppressed by midodrine 92.8 +/- 0.7 (P < 0.001), octreotide 90.6 +/- 0.78 (P < 0.001), and combination therapy 84.7 +/- 0.7 (P < 0.001). Combination therapy was better than monotherapy (P < 0.001) but only for the first 10 minutes of standing. Standing time of 36.3 +/- 3.5 minutes in the patients with OI improved with midodrine, octreotide and combination therapy (55.5 +/- 3.1, 56.5 +/- 3.5, and 56.6 +/- 3.3, respectively, P < 0.05 for each). Standing heart rate in OI was 100 +/- .76 bpm; following midodrine it was 80.3 +/- .69 (P < 0.05), following octreotide it was 84.8 +/- .86, and following combination therapy it was 71.2 +/- .9 (P < 0.01). The RR interval versus time area under the curve (The Orthostatic Index) was 21.1 +/- 4 in patients with OI. After midodrine it was 41.4 +/- 3.5 (P < 0.01), after octreotide 40.3 +/- 3.8 (P < 0.01) and after the combination it was 47.3 +/- 4.6 (P < 0.001). Midodrine and octreotide suppressed tachycardia in POTS and improved standing times in OI. The two drugs had similar potencies; combination therapy was not significantly better than monotherapy.

Patients with postural tachycardia syndrome (POTS) might be misdiagnosed with panic disorder due to shared clinical features. The first aim of our study was to investigate the relationship between symptoms of POTS and panic disorder. The second aim was to delineate clinical features distinguishing symptoms of POTS from panic disorder. A total of 11 patients with POTS and 11 control subjects participated in an IRB-approved, prospective, placebo-controlled study. The experimentally induced panic-like symptoms of POTS were systematically studied using the Acute Panic Inventory (API) questionnaire. The participants answered the questionnaire after each placebo infusion and after each of the three provoking stimuli: head-up tilt test (HUT), isoproterenol infusion (ISI), and sodium lactate infusion (SLI). API responses were summed for each subject at each time point of administration. Individual API symptoms and summed responses were analyzed for statistical significance. All patients with POTS developed symptoms of orthostatic intolerance during HUT. Pharmacologically induced symptoms subjectively mimicked spontaneous symptoms in 5 of 11 patients during ISI and in none of 11 patients during SLI. In contrast, API scores in these patients reached panic threshold in 0 of 11 following HUT, in 4 of 11 following ISI and in 4 of 11 following SLI. Individual symptoms analysis revealed that significant increase in scores was limited to the somatic symptoms of palpitations, dyspnea, and twitching or trembling. In conclusion, the symptoms of POTS are phenomenologically different and clinically distinguishable from panic disorder symptoms.

Syncope is common in children and adolescents, with 15% estimated to have had at least one syncopal episode by age 18. In recent years, an increasing number of children, especially girls at their school age, have developed unexplained syncope. The mechanism of an unexplained syncope exhibited by children is incompletely studied; the association between different hemodynamic patterns and clinical features is also not clear. The aim of the study was to investigate the hemodynamic patterns of children with unexplained syncope and to examine the clinical relevance. Two hundred and eight children [87 boys, 121 girls, aged 3 - 19 years, mean (11.66 +/- 2.72) years] were selectively recruited from May 2000 to April 2006 when they presented syncope as their main complaint at the Multi-center Network for Childhood Syncope in Beijing, Hunan Province, Hubei Province, and Shanghai of China. All of the patients underwent head-up tilt tests; data were analyzed using SPSS version 10.0 for Windows. Continuous variables were expressed as the mean +/- standard deviation. Dichotomous variables were compared through a chi(2) test. A value of P < 0.05 (two sided) was regarded as statistically significant. The age distribution of children with syncope was approximately normal. Head-up tilt tests was positive in 155 children, and the incidence of positive response of the baseline head-up tilt test for diagnosing unexplained syncope was 50.48%. The sensitivity value and diagnostic value of sublingual nitroglycerin head-up tilt test were both 74.52%. The hemodynamic pattern was normal in 53 children. The 155 children, who were positive in head-up tilt tests, showed signs of postural orthostatic tachycardia syndrome (60, 28.8%), the vasoinhibitory pattern (72, 34.6%), the cardioinhibitory pattern (5, 2.4%), and the mixed pattern (18, 8.7%). The gender distribution between the two age groups (age < 12 years vs age > or = 12 years) was not different (P > 0.05). The distribution of hemodynamic patterns between the children of the two age groups (age < 12 years vs age > or = 12 years), and the children with different complaints (dizziness vs syncope) was significantly different (P < 0.05), while the distribution between the children of different sexes and different lasting time of syncope (< or = 5 minutes vs > 5 minutes) was not significantly different (P > 0.05). Different hemodynamic patterns were differentiated by differing syncope inducements, presymptoms, and complicated symptoms during and after syncope. The tested girls were more prone when compared with the boys to have unexplained syncope, and the peak age was around twelve years old. The incidence of positive response of head-up tilt tests was also relatively higher for the girls. The distribution of hemodynamic patterns for different ages was different. For children with unexplained syncope, we should use head-up tilttests to distinguish the hemodynamic patterns in order to adopt rational therapeutic measures.

Postural tachycardia syndrome (POTS) is a disorder of unknown etiology, and patients with this condition exhibit orthostatic intolerance (OI) and excessive tachycardia. Excessive tachycardia with POTS has been defined as a rapid (within 10 minutes) increase in heart rate by more than 30 beats per minute or a heart rate that exceeds 120 beats per minute. Patients with POTS can experience difficulty with daily routines such as housework, shopping, eating, and attending work or school. The possibility exists that all forms of OI, including POTS, result from central hypovolemia even without tachycardia. The clinical findings of POTS are observed in an increasing number of patients who are usually female and aged 15 to 50 years. Adults with POTS do not have hypotension, whereas children may exhibit hypotension. Many patients with POTS are intolerant of exercise. "Idiopathic" POTS must be distinguished from other conditions that can reduce venous return to the heart and produce similar signs and symptoms such as dehydration, anemia, or hyperthyroidism. Therapies for POTS are directed at relieving the central hypovolemia or at compensating for the circulatory dysfunctions that may cause this disorder. Treatments have resulted in varying degrees of success and are often used in combination with each other.

We report the anesthetic management of a parturient with postural orthostatic tachycardia syndrome. This syndrome is associated with hemodynamic instability, which can be worsened by the physiology of labor and delivery. We discuss anesthetic concerns with this disease in the parturient and suggest approaches for management of this disease.

To test the validity and practicality of a simple, rapid autonomic cardiovascular evaluation (RACE). Assessment of the autonomic nervous system is costly and time consuming. Consequently, briefer measures are often utilized as evaluations of autonomic function. We therefore set out to assess the validity and practicality of a simple, rapid autonomic cardiovascular evaluation protocol which mimicked the bedside evaluations used in many healthcare centers. Every eligible patient undergoing full autonomic testing (FAT) in our laboratory was enrolled. The protocol, performed blinded to FAT results, consisted of one breath in the supine position, and supine and standing (1 and 3 min) pressures and pulse. Results were scored for cardiac variation during the breath, a drop in pressure during the stand. Pulse increase was also scored. Aggregate RACE score was regressed against a similarly scored FAT. The single breath response correlated poorly with the standard response to deep breathing with convergent results in only 26/37 patients, with a specificity of 30%, and sensitivity of 85%. HR and BP changes standing showed little regression against matching values during FAT. Only 5/11 patients who met the criteria for postural tachycardia syndrome by FAT demonstrated a >20 bpm increase in HR by 3 min standing. Finally, aggregate scores for FAT and RACE correlated poorly. The RACE does not satisfy the criteria to serve as a robust dysautonomia screen. Full autonomic testing provides more complete and accurate information than simple bedside assessment.

To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.

To evaluate the prevalence and pathogenetic mechanisms of postural orthostatic tachycardia syndrome (POTS). We reviewed the medical records of patients with POTS seen at the Mayo Clinic in Rochester, Minn, from January 1, 1993, through December 31, 2003. All patients were required to have had a full autonomic reflex screen. The results of the following additional tests were evaluated: thermoregulatory sweat test, plasma catecholamine measurement, serum ganglionic (a3) acetylcholine receptor antibody detection, and 24-hour urinary sodium measurement. We identified 152 patients (86.8% female; mean +/- SD age, 30.2+/-10.3 years) with a mean duration of symptoms of 4.1 years. The mean orthostatic heart rate increment was 44 beats/min. Half the patients had sudomotor abnormalities (apparent on both the quantitative sudomotor axon reflex test and thermoregulatory sweat test), and 34.9% had significant adrenergic impairment, indicating that at least half of the patients had a neuropathic pattern of POTS. In 13.8% of patients, onset was subacute, and ganglionic acetylcholine receptor antibody was detected in 14.6%, suggesting an autoimmune origin in at least 1 in 7 patients. Hyperadrenergic status was documented in 29.0% of patients (standing plasma norepinephrine level 2600 pg/mL), and at least 28.9% were presumably hypovolemic (24-hour urinary sodium level <100 mEq/24h). The lack of correlation between urinary sodium and standing norepinephrine levels suggests that mechanisms other than hypovolemia accounted for the hyperadrenergic state. Our findings suggest a neuropathic basis for at least half the cases of POTS and that a substantial percentage of cases may be autoimmune. Hyperadrenergic and hypovolemic correlates are likely compensatory or exacerbating.

To elucidate the mechanisms whereby postural tachycardia syndrome (POTS) patients maintain orthostatic blood pressure and explain the greater prevalence of female cases in POTS cohorts. We investigated muscle sympathetic nerve (MSN) discharge characteristics in 12 female POTS patients and in 9 male and 12 female control subjects using the burst amplitude distribution and the relative contribution of burst frequency and burst amplitude. At rest, burst distribution was shifted toward larger amplitudes in POTS patients (p < 0.005), consistent with increased sympathetic activity. During hypotension, the distribution shifted toward larger amplitude bursts in control subjects (p < 0.001), whereas it did not change in POTS patients. Total MSN activity increase to hypotension did not differ between subject groups, but the relative contribution of burst frequency change to the total activity increase was greater in POTS patients than in female (p < 0.05) and male (p < 0.001) control subjects. In contrast, the relative contribution of burst amplitude change to total MSN activity increase was greater in male compared with female control subjects (p < 0.05) and POTS patients (p < 0.001). At rest, the burst amplitude distribution was consistent with increased sympathetic activity in POTS and did not change in response to hypotension. In response to hypotension, burst frequency makes a proportionally greater contribution to the increase in total MSN activity in POTS patients compared with female control subjects, and female compared with male control subjects. These physiological differences in MSN discharge characteristics, in the setting of sympathetic fiber loss associated with POTS, may contribute to the predisposition to and greater prevalence of POTS in female individuals.

The postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia with chronic symptoms that are associated with upright posture. These chronic symptoms (of at least 6 months' duration) include tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache, and mental clouding. Patients with POTS demonstrate an increase in heart rate of at least 30 beats/min within 5 to 30 minutes of assuming an upright posture, in the absence of orthostatic hypotension (a fall in blood pressure >20/10 mm Hg) and in the absence of other medical disorders that might cause tachycardia. POTS can be associated with a high degree of functional disability. The blood volume has been found to be low in many patients with POTS. This article will review some of the data regarding blood volume perturbations in POTS, blood volume regulation in POTS, and potential treatment approaches.

Norepinephrine is frequently elevated in postural tachycardia syndrome (POTS), a syndrome of heterogeneous etiology characterized by a >30 beats/min increase in heart rate with standing. Norepinephrine is synthesized from dopamine by dopamine-beta-hydroxylase (DBH). The results of a preliminary study suggested that the T allele frequency of the DBH -1021C-->T polymorphism is elevated in POTS. This allele correlates with low DBH activity and might predict reduced serum DBH activity in patients with POTS. To test the hypothesis that low DBH activity and the underlying -1021C-->T polymorphism are associated with increased susceptibility to POTS, we measured serum DBH activity in POTS and determined its relationship to the DBH genotype and plasma norepinephrine. Serum DBH was similar for 83 normal volunteers and 42 patients with POTS: median (range) = 22.5 (0.5-94.2) and 19.6 (0.1-68.8) nmol.min(-1).ml(-1), respectively (P = 0.282). The genotype frequencies for 254 control and 157 POTS patients were not different between groups ( approximately 63% CC genotype and approximately 5% TT genotype, P = 0.319). The T allele associated with lower serum DBH in both groups [control serum DBH = 15.7 (SD 12.3) and 35.1 nmol.min(-1).ml(-1) (SD 18.6) for T carriers and noncarriers, respectively; POTS serum DBH = 8.2 (SD 5.6) and 28.5 nmol.min(-1).ml(-1) (SD 14.7) for T carriers and noncarriers, respectively]. High DBH in POTS was linked to elevated plasma levels of norepinephrine. Although DBH activity and genotype are unlikely to be primary determinants of susceptibility to POTS, differences in DBH activity in POTS may reflect differences in the level of sympathetic activation.