Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.

The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.

Background-Patients with postural tachycardia syndrome (POTS) experience considerable disability, but in most, the pathophysiology remains obscure. Plasma volume disturbances have been implicated in some patients. We prospectively tested the hypothesis that patients with POTS are hypovolemic compared with healthy controls and explored the role of plasma renin activity and aldosterone in the regulation of plasma volume. Methods and Results-Patients with POTS (nϭ15) and healthy controls (nϭ14) underwent investigation. Heart rate (HR), blood pressure (BP), plasma renin activity, and aldosterone were measured with patients both supine and upright. Blood volumes were measured with 131 I-labeled albumin and hematocrit. Patients with POTS had a higher orthostatic increase in HR than controls (51Ϯ18 versus 16Ϯ10 bpm, PϽ0.001). Patients with POTS had a greater deficit in plasma volume (334Ϯ187 versus 10Ϯ250 mL, PϽ0.001), red blood cell volume (356Ϯ128 versus 218Ϯ140 mL, Pϭ0.010), and total blood volume (689Ϯ270 versus 228Ϯ353 mL, PϽ0.001) than controls. Despite the lower plasma volume in patients with POTS, there was not a compensatory increase in plasma renin activity (0.79Ϯ0.58 versus 0.79Ϯ0.74 ng · mL Ϫ1 · h

Background Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community‐based survey highlights patients’ experience with POTS. It consists of the largest sample of POTS patients reported to date. Objectives To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. Methods Postural tachycardia syndrome patients completed an online, community‐based, cross‐sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. Results The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6–72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). Conclusions These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5 Ϯ 1 episodes/mo, n ϭ 14), age-and sex-matched controls (CON, n ϭ 23), and in healthy subjects who consistently experienced syncope during tilt (FS ϩ , n ϭ 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS ϩ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope. ( J. Clin. Invest. 1997. 99:2736-2744.)

IOT responds best acutely to saline infusion to correct the underlying hypovolemia. Chronically, this can be accomplished with increased salt and water intake in conjunction with fludrocortisone. The response of patients to the alpha1-agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of alpha1-agonists to pharmacologically replace lower-extremity postganglionic sympathetics is an appropriate overall goal of therapy. These findings are consistent with our hypothesis that the tachycardia and elevated catecholamine levels associated with IOT are principally due to hypovolemia and loss of adequate lower-extremity vascular tone.

Background-Short-term and tonic regulation of arterial blood pressure (BP) differ in premenopausal women and men of similar age. The autonomic nervous system (ANS) plays a critical role in BP regulation. Methods and Results-To

Abstract-Recent studies suggest that activation of the sympathetic nervous system either directly or indirectly influences cerebrovascular tone in humans even within the autoregulatory range. In 6 healthy subjects (aged 29Ϯ4 years), we used transcranial Doppler sonography to determine cerebral blood flow velocity during sympathetic activation elicited through head-up tilt (HUT) and sympathetic deactivation through ganglionic blockade. PaCO 2 was manipulated through hyperventilation and CO 2 breathing (5%). With subjects in the supine position and during HUT, mean arterial pressure was not influenced by PaCO 2 . During ganglionic blockade, mean arterial pressure decreased markedly with hyperventilation (Ϫ13Ϯ1.9 mm Hg). Manipulation of sympathetic tone elicited only mild changes in cerebral blood flow (64Ϯ5.8 cm/s supine, 58Ϯ4.9 cm/s upright, and 66Ϯ6.2 cm/s during ganglionic blockade; Pϭ0.07 by ANOVA). The slope of the regression between PaCO 2 and mean velocity was 1.6Ϯ0.18 cm/(s ⅐ mm Hg) supine, 1.3Ϯ0.14 cm/(s ⅐ mm Hg) during HUT, and 2.3Ϯ0.36 cm/(s ⅐ mm Hg) during ganglionic blockade (PϽ0.05). Spontaneous PaCO 2 and ventilatory response to hypercapnia were also modulated by the level of sympathetic activity. Changes in sympathetic tone have a limited effect on cerebral blood flow at normal PaCO 2 levels. However, the sympathetic nervous system seems to attenuate the CO 2 -induced increase in cerebral blood flow. This phenomenon may indicate a moderate direct effect of the sympathetic nervous system on the cerebral vasculature. Furthermore, sympathetic activation tends to increase ventilation and thus can indirectly increase cerebrovascular tone. (Hypertension. 2000;36:383-388.)Key Words: carbon dioxide Ⅲ baroreflex Ⅲ receptors, adrenergic Ⅲ phenylephrine Ⅲ sympathetic nervous system T he ability to assume the upright posture depends crucially on sufficient perfusion of the brain. 1,2 Blood flow to the brain can be influenced through adjustments in systemic hemodynamics (ie, perfusion pressure) or through local vascular modulation (ie, cerebral autoregulation). 3 Thus, impaired adjustment of systemic hemodynamics or disordered regulation of cerebrovascular tone could contribute to cerebral hypoperfusion with standing. An example of the former is the profound orthostatic hypotension seen in autonomic failure patients, which leads to cerebral hypoperfusion as the decrease in blood pressure (BP) exceeds the autoregulatory capacity of the brain. 1,4 On the other hand, the concept that impaired local regulation of cerebrovascular tone can also lead to cerebral hypoperfusion with standing is supported by recent findings in patients with orthostatic intolerance. [5][6][7][8] These patients experience typical symptoms of cerebral hypoperfusion when they stand, and these symptoms are associated with excessive reductions in cerebral blood flow velocity despite maintenance of arterial BP. 6 This cerebral vasoconstriction is attenuated either by interventions that blunt sympathetic activation or by ␣-adrenoreceptor blockad...