Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.

Chronic orthostatic intolerance (COI) occurs in postural tachycardia syndrome (POTS) and in some individuals with repeated neurocardiogenic syncope/presyncope (NCS), without POTS. This study addressed whether patients with COI and POTS or NCS have neurocirculatory abnormalities during supine rest. Adult patients referred for COI who had POTS (n=90, mean+/-SEM age 40+/-1 years, 86% women) or NCS (n=36, 41+/-2 years old, 78% women) underwent measurements of plasma levels of catecholamines and forearm hemodynamics. Comparison data were obtained from 32 age- and gender-matched normal volunteers (39+/-2 years old, 81% women). The POTS group had a relatively fast mean heart rate (79+/-2 bpm) during supine rest compared with the NCS group (69+/-1.6 bpm, P=0.03) and normal volunteers (66+/-3 bpm, P=0.0004). The POTS group also had higher mean arterial norepinephrine (1.61+/-0.11 nmol/L, n=37) and epinephrine (0.39+/-0.03 nmol/L, n=37) concentrations than the NCS group (1.03+/-0.12 nmol/L, n=20, P=0.0012; 0.21+/-0.03 nmol/L, n=20, P=0.0005) and normal volunteers (1.13+/-0.11 nmol/L, n=20, P=0.006; 0.17+/-0.03 nmol/L, n=15, P=0.0001). The NCS group had higher mean forearm vascular resistance (52+/-6 U) than the POTS group (36+/-2 U, P=0.003). Overall, POTS features increased heart rate and sympathetic nervous and adrenomedullary hormonal system outflows during supine rest. Increased sympathetic outflow may contribute to the relative tachycardia in POTS. NCS features forearm vasoconstriction during supine rest but not sympathoneural or adrenomedullary activation.

Previous studies have reported slow (<0.5 Hz) modulation of electroencephalographic (EEG) background amplitude and suggested that this reflects periodic neuronal activity in the brainstem, such as may be recorded from cardiovascular and respiratory centers in animals. We searched for a relationship between EEG amplitude modulation and modulation of simultaneously recorded cardiovascular variables and attempted to determine whether this relationship was altered in subjects with postural tachycardia syndrome (POTS). We recorded EEG, blood flow velocity in the middle cerebral artery (MCA), heart rate, respirations, and blood pressure from subjects with POTS and controls during head-up tilt. Time-frequency analysis of 0.512-s epochs of EEG was performed to determine peak alpha amplitude. Spectra were divided into 3 bands: ultraslow, middle, and respiratory. EEG alpha amplitude modulation in all frequency bands was reduced in POTS subjects while supine. EEG modulation decreased in controls with head-up tilt but not in POTS subjects. Heart rate modulation in the respiratory frequency band decreased with head-up tilt and was significantly less (P<0.02) in ultraslow and respiratory frequency bands in POTS subjects after head-up tilt. Blood pressure and MCA flow velocity modulation in middle and respiratory bands increased with head-up tilt to a greater degree in POTS subjects. Blood pressure and MCA flow velocity modulation frequencies were moderately correlated, but correlations between EEG and cardiovascular variable modulation frequencies were generally low, being highest in the respiratory band but not statistically significant. There are subtle differences in EEG amplitude modulation in subjects with POTS. Altered EEG amplitude modulation in POTS may reflect altered brainstem physiology in this disorder.

Recent studies suggest that water drinking elicits acute changes in human physiology. Water drinking profoundly increases blood pressure in patients with autonomic failure. Water drinking also increases blood pressure in quadriplegic patients, cardiac transplant recipients, and older healthy subjects, but to a lesser extent. Blood pressure does not change in healthy young subjects. More recently, water drinking was shown to increase energy expenditure. The acute changes in cardiovascular regulation and in energy expenditure with water drinking appear to be mediated through activation of the sympathetic nervous system. The sympathetic activation may involve a spinal reflex-like mechanism. The stimulus that causes the sympathetic activation is not known. The acute water pressor response can be exploited in the treatment of patients with impaired orthostatic tolerance caused by autonomic failure, postural tachycardia syndrome, or, perhaps, neurocardiogenic (vasovagal) syncope. The increase in energy expenditure with water drinking should be recognized as an important confounding variable in metabolic studies and may hold some promise as an adjunctive measure in the prevention or treatment of obesity.

To evaluate the role of the Schellong test (ST) in forms of orthostatic dysregulation in comparison with the tilt-table test (TT). 67 young males (mean age 22 +/- 4 years) from the military service, representing two different cohorts, were examined by ST and TT, which served as gold standard. 32 of the 67 subjects were asymptomatic while 35 had sought medical advice because of orthostatic complaints. The subjects subsequently were classified into four categories according to the TT: normal TT, orthostatic hypotension (OH), postural orthostatic tachycardia syndrome (POTS), and neurocardiogenic syncope (NCS). Chi-square test was used to calculate the sensitivity and specificity of ST in detecting forms of orthostatic dysregulation (OH, POTS and NCS). In total, TT detected 23 recruits with POTS, 16 with NCS and 2 with OH. Out of the 32 asymptomatic subjects only one was diagnosed having POTS by TT and ST, the rest had a normal ST and TT. For detecting POTS, ST sensitivity was 61% and specificity was 100% compared with TT. For detecting NCS, ST sensitivity was 31% and specificity 100% compared with the reference test, the TT. The data concerning OH could not be analyzed because of the small number of cases. In conclusion the results of our study indicate that ST can be used in first line in the diagnosis of patients with orthostatic symptoms by the medical practitioner. If the ST is normal, further examination by TT is indispensable, because sensitivity of ST concerning POTS and NCS is relatively low.

Sinus tachycardia, in the forms of four distinct rhythm disturbances, is frequently encountered in clinical practice but is often overlooked. The most common rhythm, normal sinus tachycardia, whether physiologic, pathologic or iatrogenic, is predominantly catecholamine driven, is virtually asymptomatic and is managed by identifying and treating the underlying cause. The other so-called primary sinus tachycardias, which include inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome and sinus node re-entry tachycardia, have fundamentally different clinical features, basic underlying etiologic mechanisms and treatment strategies. Differentiation of these types from normal sinus tachycardia and from other atrial arrhythmias is crucial for successful management. Accurate diagnosis and appropriate therapy of the sinus tachycardias not only prevents multiple consultations but might also have important long-term prognostic implications.

Recurrent syncope may be either a sign or a symptom and may occur due to a wide variety of very different causes. Extensive investigations into the nature of this disorder soon uncovered that it represents only one aspect of a broad, heterogenous group of disturbances of the autonomic nervous system (ANS) that can result in hypotension, orthostatic intolerance, and often syncope. Disorders of orthostatic regulation may be subgrouped into both primary and secondary forms. In primary autonomic failure syndromes, as opposed to the intermittent periods of hypotension seen in the reflex syncopes, patients could develop orthostatic intolerance due to a failure of the ANS to function under normal circumstances. Chronic autonomic insufficiency has two entities: Pure Autonomic Failure (PAF) and Multiple System Atrophy (MSA). Over the last several years, it has become apparent that a milder form of autonomic insufficiency occurs that is now referred to as the Postural Orthostatic Tachycardia Syndrome (POTS). The secondary forms of autonomic failure occur in association with a particular disease process. One of the most important things to remember are the vast number of pharmacologic agents that may either cause or worsen orthostatic hypotension. The principal feature that all of these conditions share is that normal cardiovascular regulation is disturbed resulting in postural hypotension. The comerstone of evaluation is a detailed history and physical examination. One of the physician's most important tasks is to identify whether hypotensive syncope is primary or secondary in nature, and to determine if there are any potentially reversible causes (i.e., drugs, anemia, volume depletion). It is equally important to educate the patient. Nonpharmacologic therapies are useful. Pharmacotherapy should be used cautiously in selected cases.

Increased central sympathetic activity and/or deficient peripheral sympathetic nerve function are among the proposed pathophysiological changes in patients with the postural tachycardia syndrome (POTS). Little is known about sympathetic nerve outflow and its role in hemodynamic control in this disorder. We recorded peroneal muscle sympathetic nerve activity in 9 POTS patients and 9 control subjects at rest and during a nitroprusside-induced hypotensive stimulus. Baseline blood pressure (BP) and heart rate were significantly higher in POTS patients than in controls. At rest, the burst frequency was similar in POTS patients and controls (18.1+/-6.2 and 20.1+/-7.9 bursts/min, respectively; P=NS), whereas the burst incidence was significantly lower (23.1+/-6.8 versus 32.2+/-11.4 bursts/100 heartbeats, P<0.05). Nitroprusside increased sympathetic outflow significantly more in POTS patients than in controls despite a similar BP decrease (burst frequency 20.4+/-7.5 versus 12.1+/-4.1 bursts/min, P=0.008, and burst incidence 21.8+/-8.4 versus 14.4+/-5.2 bursts/100 heartbeats, P=0.03). The change in mean burst area, a measure of the number of actively firing sympathetic neurons, was similar in patients and controls (117+/-15% versus 114+/-21%, P=NS). At rest, the tachycardia and normal burst frequency result in normal or even elevated BP in POTS patients. During a hypotensive stimulus, cardiovascular homeostasis is maintained by the increased sympathetic outflow and normal heart rate response despite the lack of concomitant increase in mean burst area that is most likely due to sympathetic denervation.

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.

Water drinking recently has been shown to raise blood pressure in normal subjects and in patients with autonomic failure who have orthostatic hypotension. However, in normal young subjects, ingestion of approximately 500 ml has no pressor effect; but in older subjects there is an increase in blood pressure. An even greater rise in blood pressure occurs in cases with autonomic failure. The possible mechanisms responsible for the pressor response to water include neural and humoral factors; fluid redistribution also needs to be considered. This review will concentrate on the water pressor response in normal subjects and different groups of patients with autonomic diseases who have orthostatic intolerance, on the mechanisms that could be involved, and on whether this pressor response may be used in the management of orthostatic hypotension, vasovagal syncope and the postural tachycardia syndrome.

Fibromyalgia (FM) is a major determinant of poor health status in systemic lupus erythematosus (SLE). FM has been shown to be associated with neurally mediated hypotension (NMH) in the general population, in which effective treatments exist. We explored whether NMH was more common in SLE patients with FM than those without. Seventy-six SLE patients (4 male, 72 female; 1 ethnic Indian, 28 African American, 47 Caucasian; mean age 40.2 +/- 9.4 yr) were recruited and their FM status ascertained using American College of Rheumatology (ACR) classification criteria. Patients who were pregnant or deconditioned were excluded. A two-stage tilt-table test was used to detect NMH. All patients completed the SF-36 Heath Status Inventory (SF-36) and the Krupp Fatigue Severity Scale (KFSS) to evaluate their quality of life. Serological markers and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were recorded. Medications that might interfere with testing were temporarily withheld before the tilt-table test. The prevalence of NMH (first stage) in SLE patients was 47.9%. Seven patients had both NMH and postural orthostatic tachycardia syndrome. Two patients had borderline results with symptoms reproduced but an inadequate drop in systolic blood pressure by definition (a drop of at least 25 mmHg defines an abnormal response). Eighteen (23.7%) SLE patients had FM and 51 (67.1%) had at least one tender point (TP). The frequency of NMH (first or second stage) in SLE with FM was 58.3% compared with 69.4% in SLE without FM (odds ratio 0.62, 95% CI 0.16-2.37). SF-36 and KFSS scores were not significantly different in SLE patients with and without NMH. However, both scores were found to be associated with FM status (P<0.001 and P = 0.014), reflecting poor health status in the FM group. No confounding variable was found to be significantly associated with both NMH and FM. NMH is common in SLE patients with a high prevalence rate. The large increase in NMH, a form of autonomic neuropathy, in SLE, has not been explained. However, NMH has no impact on quality of life above that determined by FM, and has no statistically significant association with FM status. Identification of NMH may be important in selected patients with SLE who have chronic fatigue, but NMH cannot explain the increased prevalence of FM in SLE.

The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF). Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS). Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83+/-1.78 (healthy group -7.60+/-5.41) ( P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity. A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.

Autonomic imbalance may work as a modifying factor for initiating lethal arrhythmia in patients with Brugada syndrome. A 26-year-old man with episodes of near syncope was given a diagnosis of an autonomic disorder, postural orthostatic tachycardia syndrome (POTS). The patient spontaneously showed typical Brugada-type ECG, and ventricular fibrillation was induced by programmed electrical stimulation, which allowed the further diagnosis of Brugada syndrome. Although it seems that Brugada syndrome is asymptomatic, its uncommon association of POTS may increase the risk for future arrhythmic events in this patient.

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found that blood flow was linearly correlated (r(p) = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3 in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients.

There are a number of distal and generalized small-fiber neuropathies. The neuropathologic basis is poorly understood as somatic and autonomic C fibers are not usually studied in the same region of the body. To evaluate prospective somatic and autonomic C-fiber function in 11 healthy control subjects and 38 patients with different clinical patterns of neuropathy. Distal small-fiber neuropathy (DSFN), peripheral neuropathy (PN), diabetic neuropathy (DN), neuropathic postural tachycardia syndrome (POTS), and idiopathic autonomic neuropathy (IAN) were evaluated. Intraepidermal nerve fiber density was used to evaluate distal somatic C fibers. Both quantitative sudomotor axon reflex test and skin norepinephrine content were measured for the biopsy site to assess distal autonomic C-fiber function. Postganglionic sudomotor, adrenergic, and cardiovagal functions were evaluated by autonomic reflex testing and quantified using a Composite Autonomic Severity Scale. Skin norepinephrine concentration was significantly related to CASS. DN was associated with somatic and autonomic C-fiber impairment with good agreement. POTS was associated with selective distal autonomic deficit. DSFN had combined distal somatic and C-fiber impairment. IAN showed combined and selective distal and generalized autonomic C-fiber impairment. The somatic neuropathies had C-fiber impairment affecting both populations to varying degrees. Although a general agreement exists between the loss of somatic C fibers and autonomic deficits, selective involvement occurs for specific autonomic neuropathies.

This paper discusses the development of a system to measure continuous cardiac baroreceptor measurement during a 45-minute 70-degree head-up tilt (HUT) of five groups of subjects suffering the following: chronic fatigue syndrome (CFS), CFS with fibromyalgia (CFS-FM), CFS with postural orthostatic tachycardia syndrome (CFS-POTS), controls with POTS (CON-POTS), and controls (CON). The duration of the test was 56-minutes, which included a five-minute supine baseline, a 45-minute HUT and a six-minute recovery period. The system was developed in LabView, and can provide a comparative time analyses of weighted BRSI averages. Baroreflex effectiveness index (BEI) was also investigated over the course of lags 0, 1 and 2 as well as an assessment of overall BEI performance between groups.

Postural Orthostatic Tachycardia Syndrome (POTS) is a type of orthostatic intolerance that is characterized by excessive tachycardia and decreased cerebral blood flow in the upright position. This can result in significant symptoms of dizziness and light-headedness that can eventually lead to syncope. In this review, we describe two patients with POTS that varied in their degree of symptoms and treatment. One patient was able to be treated as an outpatient, while the other required hospitalization and extensive medical therapy. We would like to emphasize with this review that POTS is probably more common than it is diagnosed and is often confused with other conditions, such as chronic fatigue syndrome or functional syncope. It is important to make the correct diagnosis in order to allow appropriate treatment and to improve the quality of life for these patients.

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.

The study investigated correlates of functional disability in 94 patients (89.4% women, 10.6% men; mean age=34.2 years) with postural tachycardia syndrome (POTS), a clinical syndrome of orthostatic intolerance characterized by significant functional limitations. Path analysis supported a model in which, controlling for demographic and disease variables, catastrophic cognitions were directly related to the latent variable functional disability, whereas somatic vigilance, anxiety sensitivity, and neuroticism were indirectly associated with functional disability through their relationship with catastrophic cognitions. Results suggest that modifiable psychological factors play a role in the functional limitations experienced by patients with POTS. Longitudinal research is necessary to confirm these relationships.

Four women age 17 to 28 years presented with orthostatic headaches as the most prominent feature of their symptom complex. None had CSF leak or intracranial hypotension. Autonomic studies showed evidence of orthostatic intolerance with tachycardia in all cases. Treatment of orthostatic intolerance, mainly with volume expansion, was only partially effective. Orthostatic headaches are not always caused by CSF leak or supine intracranial hypotension. Occasionally they may be the major clinical manifestation of postural tachycardia syndrome or orthostatic intolerance.

Postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia are two clinically different entities but with significant overlap of symptoms. Treatment by and large is medical; however, other modalities of treatment are being evaluated.

Extraarticular manifestations of the joint hypermobility syndrome may include the peripheral nervous system. The purpose of this study was to investigate autonomic function in patients with this syndrome. Forty-eight patients with the joint hypermobility syndrome who fulfilled the 1998 Brighton criteria and 30 healthy control subjects answered a clinical questionnaire designed to evaluate the frequency of complaints related to the autonomic nervous system. Next, 27 patients and 21 controls underwent autonomic evaluation: orthostatic testing, cardiovascular vagal and sympathetic functions, catecholamine levels, and adrenoreceptor responsiveness. Symptoms related to the autonomic nervous system, such as syncope and presyncope, palpitations, chest discomfort, fatigue, and heat intolerance, were significantly more common among patients. Orthostatic hypotension, postural orthostatic tachycardia syndrome, and uncategorized orthostatic intolerance were found in 78% (21/27) of patients compared with in 10% (2/21) of controls. Patients with the syndrome had a greater mean (+/- SD) drop in systolic blood pressure during hyperventilation than did controls (-11 +/- 7 mm Hg vs. -5 +/- 5 mm Hg, P = 0.02) and a greater increase in systolic blood pressure after a cold pressor test (19 +/- 10 mm Hg vs. 11 +/- 13 mm Hg, P = 0.06). Patients with the syndrome also had evidence of alpha-adrenergic (as assessed by administration of phenylephrine) and beta-adrenergic hyperresponsiveness (as assessed by administration of isoproterenol). The autonomic nervous system-related symptoms of the patients have a pathophysiological basis, which suggests that dysautonomia is an extraarticular manifestation in the joint hypermobility syndrome.

Postural tachycardia syndrome (POTS) is related to defective peripheral vasoconstriction of dependent extremities with redistributive hypovolemia. To test whether enhanced microvascular filtration produces leg enlargement, we studied 12 patients 13 to 19 years of age with POTS and defective leg vasoconstriction and 13 age-matched healthy control subjects, with strain-gauge plethysmography used to measure venous pressure (Pv), forearm and calf blood flow, vascular capacitance, and the microvascular filtration coefficient (Kf). Measurements were made while the patient was supine and at steady state during upright tilt to 35 degrees. Supine Pv was not different in POTS, but upright leg Pv tended to be increased above control. Arm and leg peripheral arterial resistance was decreased in the supine and upright positions in patients with POTS compared with control subjects (P=0.01, upright legs). Supine Kf was not significantly increased in the forearm in patients with POTS but was increased in the calf (9.3+/-2.2 versus 5.7+/-2.4 [10(-3)] mL/100 mL per minute per mm Hg, P=0.04), correlating with calf blood flow (rs=0.84, P=0.002). Kf was invariant with orthostasis. The hydraulic contribution to upright filtered flow at 35 degrees tilt, the product of Kf and Pv, was approximately twice that of control (0.41+/-0.09 versus 0.19+/-0.04 mL/100 mL per minute, P=0.04). Increased microvascular filtration accounts for enhanced leg swelling in patients with POTS with increased arterial blood flow.

A relatively novel group of drugs that inhibit the funny current in the sinus node pacemaker cells, the so-called specific bradycardic agents, are likely to play a significant role in the management of a wide range of cardiovascular disorders, including the sinus tachyarrhythmias. This comprehensive review initially provides an insight into these agents, their historical background, and their mechanism of action. It then discusses the differential diagnosis of the sinus tachyarrhythmias (normal sinus tachycardia, inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and sinus node reentry tachycardia), elaborates on their pathophysiologic basis, and provides up-to-date evidence-based information on their optimum management. The specific bradycardic agents, by the very nature of their mode of action, may prove ideal therapies for the management of the sinus tachyarrhythmias, and this is explored at every stage.

In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53+/-0.07 nmol/l) and dihydroxyphenylglycol (6.52+/-0.46 nmol/l) than did control subjects (0.90+/-0.09 and 9.64+/-0.46 nmol/l respectively; P =0.0001). The MSA+OH group had higher plasma levels of both catechols (noradrenaline, 1.31+/-0.16 nmol/l; dihydroxyphenylglycol, 5.08+/-0.43 nmol/l) than did the PAF group (noradrenaline, 0.38+/-0.08 nmol/l; dihydroxyphenylglycol, 2.53+/-0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71+/-0.64 nmol/l; dihydroxyphenylglycol, 10.41+/-1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA+OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.