Idiopathic Orthostatic Intolerance Research Articles

Postural tachycardia syndrome: multiple symptoms, but easily missed

The evolution of upright posture is usually considered an advantage in humans. For people with postural tachycardia syndrome (PoTS) it can present a daily challenge. Although orthostatic intolerance is often associated with older people, PoTS tends to affect young women who present with multiple, non-specific symptoms and significant functional impairment.1 PoTS was characterised in 1993,2 but previously existed under various names including irritable heart, soldier's heart, and idiopathic orthostatic intolerance. It is a heterogeneous group of disorders sharing similar characteristics as a consequence of abnormal autonomic nervous system response to assuming upright posture. When humans stand up, approximately 500 ml of blood descends from the thorax into the abdominal cavity and limbs. A normal autonomic nervous system responds with immediate peripheral vasoconstriction, increase in heart rate of 10–20 beats per minute (bpm), and minimal change in blood pressure.1 In patients with PoTS this mechanism does not respond appropriately; the exact pathophysiology remains unclear.3 A likely mechanism is inadequate vasoconstriction on standing, resulting in pooling of blood in splanchnic and peripheral vasculature. Heart rate and catecholamine levels increase further to compensate. Symptoms of cerebral hypoperfusion including dizziness and syncope occur, often in the presence of normal blood pressure. Ironically, some patients with PoTS have a hypertensive response to standing.1 Diagnosis is usually made following a tilt table test or 10-minute stand test. The definition is arbitrary, but agreed by consensus (Box 1).4 Heart rate increases but, by definition, blood pressure does not necessarily drop. However, there is overlap with neurally mediated hypotension and some …

Microgravity and cardiac atrophy: no sex discrimination

mans’ continued initiative in space exploration will tax the human body, including the cardiovascular system. This system is exquisitely sensitive to loading conditions and neurohormonal stimuli and is adapted to function in normal gravitational environments (1 G). Both mechanical (muscle and

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Idiopathic orthostatic intolerance (IOI) is a common disorder that is characterized by chronic orthostatic symptoms and substantial increases in heart rate and plasma norepinephrine concentrations that are disproportionately high while standing. Several features of the syndrome, including the tachycardia, tremulousness, and exaggerated norepinephrine have been considered potentially due to hypoactive or hyperactive states of adrenergic receptors of the sympathetic nervous system. The aim of this study was therefore to ascertain whether genotypes at eight polymorphic loci within five relevant adrenergic receptor genes (alpha2A, alpha2B, alpha2C, beta1 and beta2) influence the risk for IOI. We studied 80 young men in military service (20 patients with IOI and 60 age-matched controls). All participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. Genotyping at the eight loci (alpha2ALys251, alpha2BDel301-303, alpha2CDel322-325, beta1Gly49, beta1Arg389, beta2Arg16, beta2Glu27, beta2Ile164) was performed in all participants. Chi-square tests of independence were used to test for associations between IOI and genotype. In addition, an association of the polymorphisms with haemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way variance analysis. For the beta1Gly49 polymorphism we found a decrease in the risk of IOI among persons who were homozygous (odds ratio, 0.88; 95% confidence interval, 0.81-0.97). In addition, we found an association between beta1Gly49 and decreased heart rate in the upright position, regardless of IOI diagnosis. There were no associations with the other studied polymorphisms and IOI. Our current results suggest that the beta1Gly49 polymorphism is protective for IOI. This is likely one of several common genetic loci that may represent modifiers of IOI phenotypes.

Exercise training and orthostatic intolerance: a paradox?

Exercise training and orthostatic intolerance: a paradox?

Limb venous compliance in patients with idiopathic orthostatic intolerance and postural tachycardia.

Venous denervation and increased venous pooling may contribute to symptoms of orthostatic intolerance. We examined venous compliance in the calf and forearm in 11 orthostatic-intolerant patients and 15 age-matched controls over a range of pressures, during basal conditions and sympathetic excitation. Occlusion cuffs placed around the upper arm and thigh were inflated to 60 mmHg and deflated to 10 mmHg over 1 min. Limb volume was measured continuously with a mercury-in-Silastic strain gauge. Compliance was calculated as the numerical derivative of the pressure-volume curve. The pressure-volume relationship in the upper and lower extremities in the basal and sympathetically activated state was significantly lower in the orthostatic-intolerant patients (all P < 0.05). Sympathoexcitation lowered the pressure-volume relationship in the lower extremity in patients (P < 0.001) and controls (P < 0.01). Venous compliance was significantly less in patients in the lower extremity in the basal state over a range of pressures (P < 0.05). Venous compliance was less in patients compared with controls in the upper (P < 0.005) and lower extremities (P < 0.01) in the sympathetically activated state, but there were no differences at individual pressure levels. Sympathetic activation did not change venous compliance in the upper and lower extremity in patients and controls. Patients with orthostatic intolerance have reduced venous compliance in the lower extremity. Reduced compliance may limit the dynamic response to orthostatic change and thereby contribute to symptoms of orthostatic intolerance in this population group.

Water drinking as a treatment for orthostatic syndromes

PurposeWater drinking increases blood pressure in a substantial proportion of patients who have severe orthostatic hypotension due to autonomic failure. We tested the hypothesis that water drinking can be used as a practical treatment for patients with orthostatic and postprandial hypotension, as well as those with orthostatic tachycardia. Subjects and methodsWe studied the effect of drinking water on seated and standing blood pressure and heart rate in 11 patients who had severe orthostatic hypotension due to autonomic failure and in 9 patients who had orthostatic tachycardia due to idiopathic orthostatic intolerance. We also tested the effect of water drinking on postprandial hypotension in 7 patients who had autonomic failure. Patients drank 480 mL of tap water at room temperature in less than 5 minutes. ResultsIn patients with autonomic failure, mean (± SD) blood pressure after 1 minute of standing was 83 ± 6/53 ± 3.4 mm Hg at baseline, which increased to 114 ± 30/66 ± 18 mm Hg (P <0.01) 35 minutes after drinking. After a meal, blood pressure decreased by 43 ± 36/20 ± 13 mm Hg without water drinking, compared with 22 ± 10/12 ± 5 mm Hg with drinking (P <0.001). In patients with idiopathic orthostatic intolerance, water drinking attenuated orthostatic tachycardia (123 ± 23 beats per minute) at baseline to 108 ± 21 beats per minute after water drinking ( P <0.001). ConclusionWater drinking elicits a rapid pressor response in patients with autonomic failure and can be used to treat orthostatic and postprandial hypotension. Water drinking moderately reduces orthostatic tachycardia in patients with idiopathic orthostatic intolerance. Thus, water drinking may serve as an adjunctive treatment in patients with impaired orthostatic tolerance.

Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity.

Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P<0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.

Abnormal baroreflex responses in patients with idiopathic orthostatic intolerance.

Patients diagnosed with idiopathic orthostatic intolerance report symptoms of lightheadedness, fatigue, and nausea accompanied by an exaggerated tachycardia when assuming the upright posture. Often, these symptoms are present in the absence of any decrease in arterial pressure. We hypothesized that patients with idiopathic orthostatic intolerance would have impaired cardiac vagal and integrated baroreflex function, lower blood volume, and increased venous compliance. Sixteen patients and 14 healthy control subjects underwent the modified Oxford technique to assess cardiac vagal baroreflex sensitivity. Progressive lower-body negative pressure (to -50 mm Hg; LBNP) was used to examine the integrated baroreflex response to progressive hypovolemic stimuli. Blood volume and venous compliance were also assessed. Patients with idiopathic orthostatic intolerance had lower cardiac vagal baroreflex sensitivity (12+/-1 versus 25+/-4 ms/mm Hg; P</=0.01). The integrated baroreflex response to low levels of LBNP was characterized by shorter R-R intervals and more symptoms such as lightheadedness, despite similar levels of blood pressure. There was a trend toward lower blood volume in the patient group (56+/-2 versus 63+/-3 mL/kg; P=0.054). Patients with idiopathic orthostatic intolerance have lower cardiac vagal baroreflex sensitivity and marginally lower blood volume and respond with faster heart rates despite similar levels of arterial pressure during LBNP. These findings may contribute to the exaggerated postural tachycardia and symptoms observed in patients with this disorder.

Neuropathic Postural Tachycardia Syndrome -- What's the Defect?

The neuropathic postural tachycardia syndrome (also known as idiopathic orthostatic intolerance) consists of orthostatic symptoms that occur upon

Interaction of Genetic Predisposition and Environmental Factors in the Pathogenesis of Idiopathic Orthostatic Intolerance

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

Effects of standing on cerebrovascular resistance in patients with idiopathic orthostatic intolerance

PURPOSE: Patients with idiopathic orthostatic intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of orthostatic hypotension. SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic orthostatic intolerance (nine women, one man, 22 to 47 years) and nine age- and sex-matched control subjects. RESULTS: In patients, mean (± SD) arterial pressure at 0° head-up tilt was 90 ± 11 mm Hg and was well maintained at all tilt angles (90 ± 11 mm Hg at 75°). In controls, mean arterial pressure was 85 ± 7 mm Hg at 0° and 82 ± 11 mm Hg at 75° head-up tilt. There was a substantial decrease in peak velocity with increasing tilt angle in patients (28% ± 10%) but not in controls (10% ± 10% at 75°, P <0.001). Similarly, mean velocity decreased 26% ± 13% in patients and 12% ± 11% in controls ( P = 0.01). With increasing head-up tilt, patients had a significantly greater increase in regional cerebrovascular resistance than controls. CONCLUSIONS: In patients with idiopathic orthostatic intolerance, peak and mean middle cerebral artery blood flow velocity decreased in response to head-up tilt despite well sustained arterial blood pressure. These observations indicate that in this group of patients, regulation of cerebrovascular tone may be impaired and might therefore be a target for therapeutic interventions.