Orthostatic Symptoms Research Articles

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = -25.7 +/- 13.0 mmHg vs. -4.9 +/-14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease-specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked.

Space motion sickness: The sensory motor controls and cardiovascular correlation

Space motion sickness: The sensory motor controls and cardiovascular correlation

Inspiratory Resistance, Cerebral Blood Flow Velocity, and Symptoms of Acute Hypotension

Symptoms of orthostatic intolerance, e.g., following prolonged bed rest and microgravity exposure, are associated with reductions in cerebral blood flow. We tested the hypothesis that spontaneously breathing through an impedance threshold device (ITD) would attenuate the fall in cerebral blood flow velocity (CBFV) during a hypotensive orthostatic challenge and reduce the severity of reported symptoms. While breathing through either an active ITD (-7 cm H2O inspiratory impedance) or a sham ITD (no impedance), 19 subjects performed a squat stand test (SST). Symptoms upon stand were recorded on a 5-point scale (1 = normal; 5 = faint) of subject-perceived rating (SPR). To address our hypothesis, only data from symptomatic subjects (SPR > 1 during the sham trial) were analyzed (N = 9). Mean arterial blood pressure (MAP) and mean CBFV were measured continuously throughout the SST and analyzed in time and frequency domains. Breathing with the active ITD during the SST reduced the severity of orthostatic symptoms in eight of the nine symptomatic subjects (sham ITD SPR, 1.9 +/- 0.1; active ITD SPR, 1.1 +/- 0.1), but there was no statistically distinguishable difference in the reduction of mean CBFV between the two trials (sham ITD, -39 +/- 3% vs. active ITD, -44 +/- 3%). High frequency oscillations in mean CBFV, however, were greater during the active ITD trial (7.8 +/- 2.6 cm x s(-2)) compared with the sham ITD trial (2.5 +/- 0.9 cm x s(-2)). Higher oscillations in CBFV while breathing with the active ITD may account for the reduction in symptom severity during orthostatic hypotension despite the same fall in absolute CBFV.

Postural Tachycardia Syndrome

When a person stands up, he or she assumes that the body will automatically make any changes necessary to compensate for the increased gravitational stress this change of position brings. Indeed, standing causes gravity to try to pull nearly one quarter of the body’s blood downward toward the lower arms, legs, and abdomen, reducing the amount of blood available to keep the brain supplied with oxygen. To maintain a constant oxygen supply to the brain and upper body, standing is normally accompanied by an automatic increase in heart rate and the force with which the heart contracts and, most important, a tightening of the blood vessels in the lower part of the body. The combination of these 3 actions pushes blood upward against the force of gravity, thereby maintaining an uninterrupted flow of blood to the brain. The aspect of the nervous system that governs these …

Indices of orthostatic intolerance following 10 days of bedrest in healthy, older men and women

Moving from a supine to standing position (orthostasis) requires multiple cardiovascular and autonomic adjustments to maintain blood pressure and cerebral perfusion. We examined cardiovascular and catecholamine responses to a standardized orthostatic challenge before and after 10 d of bedrest in healthy men and women (n = 24) aged 55 – 80 y. The orthostatic test involved measurements of heart rate, blood pressure, and serum catecholamines during 10 min of supine rest followed by 10 min of standing. A test was terminated if the subject experienced any orthostatic symptoms (e.g. lightheadedness). Two subjects were symptomatic during pre‐bedrest testing, while 5 subjects were symptomatic post‐bedrest. Heart rate during the standing portion of the test was higher than the supine value; the difference between standing and supine values was significantly greater at post‐ vs. pre‐bedrest (22.3 ± 9.7 vs. 14.1 ± 15.8 bpm, respectively, p = 0.01). The difference between standing and supine serum norepinephrine values was also higher at post‐ vs. pre‐bedrest (282.6 ± 167.0 vs. 162.8 ± 271.0 pg/mL, p = 0.05). No significant differences in blood pressure or epinephrine concentration were observed. These data indicate that 10 d of bedrest can result in greater indices of orthostatic intolerance in previously asymptomatic healthy older adults. NIH P01AG023591, M01RR14288, and M01RR00073.

Orthostatic symptoms, blood pressure and working postures of factory and service workers over an observed workday

North American workers usually stand while working, and prolonged standing is associated with discomfort and cardiovascular problems. Moving may alleviate the problems, but optimum mobility is unknown. The effects of variations in mobility were explored among (1) 34 health care workers whose symptoms of orthostatic intolerance (OI) were recorded after work; (2) 45 factory and laundry workers. Postures were observed over a workday and blood pressure (BP) and heart rate (HR) of both groups were recorded before and after work. Among health care workers, 65% manifested OI symptoms. In a multiple logistic regression, presence of ⩾1 symptom of OI was associated with static postures and being female ( p=0.001). More static standing was associated with a larger drop in BP ( p=0.04) in both populations. The results suggest that more static standing postures are associated with OI and musculoskeletal symptoms and with a subclinical drop in BP.

Fibromyalgia and sleep-disordered breathing: the missing link

Recently, Martinez-Lavin [1] proposed a model of sympathetically maintained neuropathic pain syndrome that has the merit of scrutinizing possible mechanisms behind the central sensitization model [2]. Eisinger [3], in an editorial comment, raises the issue of heterogeneity permeating Martinez-Lavin's proposition. Since it is difficult to establish a traumatic trigger event in all cases, Eisinger considers multicausality as more reasonable than a single post-traumatic etiology for all cases. Felix and Fontenele [4] further explored this venue, speculating that the orthostatic intolerance symptoms seen in the majority of fibromyalgia patients are a consequence of sympathetic hyperactivity. The idea that a COMT val-158-met polymorphism may cause higher cathecolamine levels has been explored [5]. Loevinger and colleagues [6] have shown that the metabolic syndrome is more common in individuals with fibromyalgia who also have higher body mass index, blood pressure, and waist-to-hip ratio than controls. Interestingly, elevated body mass index, blood pressure, and waist-to-hip ratio are associated with sleep-disordered breathing. We recently reported in a study that 50% of the women with obstructive sleep apnea syndrome or upper airway resistance syndrome had chronic pain and more than 11 tender points when pressed with 4 kgf/cm2 [7]. Guille-minault and colleagues [8] reported orthostatic intolerance in patients with upper airway resistance syndrome. We believe that the authors investigating this theme should discuss the possibility of sleep-disordered breathing being the missing link between fibromyalgia, pain, disturbed sleep, alpha-delta sleep, hypotension, sympathetic hyperactivity, and metabolic syndrome. We are conducting investigations into whether exposition to the typical stress of sleep-disordered breathing – with repeated arousal episodes and hypoxemia – has fibromyalgia as a possible outcome. Our preliminary results underline the need to consider and further explore this hypothesis.

Mild autonomic dysfunction in primary Sjögren's syndrome: a controlled study

IntroductionThe aim of this study was to compare cardiovascular autonomic nervous system function in patients with primary Sjögren's syndrome (pSS) with that in control individuals, and to correlate the findings with autonomic symptoms and the presence of exocrine secretory dysfunction.MethodsTwenty-seven female patients with pSS and 25 control individuals completed the COMPASS (Composite Autonomic Symptom Scale) self-reported autonomic symptom questionnaire. Beat-to-beat heart rate and blood pressure data in response to five standard cardiovascular reflex tests were digitally recorded using a noninvasive finger pressure cuff and heart rate variability was analyzed by Fourier spectral analysis. Analysis was performed by analysis of variance (ANOVA), multivariate ANOVA and repeated measures ANOVA, as indicated. Factor analysis was utilized to detect relationships between positive autonomic symptoms in pSS patients.ResultsMultiple, mild autonomic disturbances were observed in pSS patients relating to decreased heart rate variability, decreased blood pressure variability and increased heart rate, which were most evident in response to postural change. There was a strong trend toward an association between decreased heart rate variability and increased severity of the secretomotor, orthostatic, bladder, gastroparesis and constipation self-reported autonomic symptom cluster identified in pSS patients. This symptom cluster was also associated with fatigue and reduced unstimulated salivary flow, and therefore may be an important component of the clinical spectrum of this disease.ConclusionThere was evidence of mild autonomic dysfunction in pSS as measured with both cardiovascular reflex testing and self-reported symptoms. Pathogenic autoantibodies targeting M3 muscarinic receptors remain a strong candidate for the underlying pathophysiology, but practical assays for the detection of this autoantibody remain elusive.

Orthostatic Hypotension for People with Spinal Cord Injuries

Abstract Orthostatic (postural) hypotension (OH) is a clinical feature commonly seen in spinal cord injury (SCI) subjects with cervical and high thoracic lesions. It usually gets worse during head-up tilt postural change and is relieved by lying flat. The mechanisms of regulating the arterial blood pressure (BP) are complex. Normally, BP is maintained through a rapid and effective reflex adjustment of the autonomic nervous system, and with slower humoral compensatory changes to counteract the gravitational forces on blood. The leg muscle pumping mechanism also helps to facilitate venous return and improves BP. Failure of these mechanisms may lead to OH and orthostatic intolerance symptoms. The occurrence of OH may limit active participation in intense physical rehabilitation programmes by people with SCI, and facilitate the deterioration effects of immobilization and development of undesirable secondary medical complications. Advances in understanding the pathophysiology of OH are crucial for success in combating OH. Treatment usually includes both non-pharmacological and pharmacological measures. This article provides a review of the mechanisms of normal regulation of arterial BP, the pathophysiology of OH in SCI, and the common clinical management of OH.

めまいの発症機序を考える 自律神経異常の関与

Patients with orthostatic dysregulation (OD)-associated disease may show autonomic disorders more frequently as compared with patients with other types of dizziness. However, the pathological mechanisms of OD remain unclear. We examined the cardiovascular autonomic function in dizzy patients with postural orthostatic tachycardia syndrome (POTS) or chronic orthostatic intolerance (OI) in order to evaluate the contribution of the autonomic disorders to the occurrence of dizziness. Heart rate variability analysis during the Schellong test showed that patients with POTS have hypo-parasympathetic function and relative hyper-sympathetic function, and that some patients with OI also have hypo-parasympathetic function. In our clinic, single therapy with a β1-blocker (Atenolol) for patients with POTS or single therapy with an a- agonist for patients with OI relieved orthostatic symptoms in 60% of the patients with POTS and OI. Further clinical studies on OD-associated disease to evaluate methods for accurate diagnosis and appropriate combined physical and pharmacotherapy may improve the outcomes in patients with OD-associated disease.

Postural orthostatic tachycardia syndrome: an underrecognized disorder

Postural orthostatic tachycardia syndrome (POTS), a clinical syndrome of orthostatic intolerance characterized by excessive tachycardia and symptoms of cerebral hypoperfusion on standing, is not well recognized in Australia. The aim was to study the clinical symptomatology, results of autonomic testing and outcome in patients with POTS. Sixteen subjects from a tertiary referral centre who met the criteria for POTS were studied between January 2003 and January 2006. Ten of these patients consented to be interviewed using a validated autonomic symptom questionnaire. Heart rate responses to deep breathing and the Valsalva manoeuvre were measured using Colin BP-508 machine (WR Medical Electronic Co., Stillwater, MN, USA). Tilt studies were carried out for 10 min to 80 degrees of head-up tilting. Patient outcome was assessed as functionally normal, able to stand 30 min without symptoms, able to work and carry out recreational activities or worse on follow up. The mean age of 10 subjects was 24.9 +/- 6.8 years, six being women. The mean duration of symptoms was 70.7 months (range 3-228 months). The common presenting orthostatic symptoms were light-headedness (100%), palpitations (90%), pallor (90%), weakness (80%) and clammy skin (80%). The mean heart rate increment during the tilt study was 51.7 +/- 14.3 b.p.m. The mean duration of follow up was 8.9 months (range 1-16 months). Only five patients were functioning normally at the follow-up visit. POTS is an underrecognized but persistent autonomic disorder in young patients with a variety of symptoms and variable outcome.

Renal sodium handling in patients with normal pressure glaucoma

Low BP (blood pressure) is a recognized risk factor for some patients with NPG (normal pressure glaucoma). We have shown previously that patients with orthostasis have impaired circadian renal handling of sodium, which may contribute to the low BP. Therefore the aim of the present study was to examine the renal handling of sodium, the circadian variations in BP and the neurohormonal response to an orthostatic test in a selected subpopulation of 18 patients with NPG with vasospastic and orthostatic symptoms, and in 24 healthy control subjects. The variations in BP and renal tubular sodium handling were evaluated using 24 h ambulatory BP recordings, 24 h urine collections and determination of endogenous lithium clearance as a marker of proximal sodium reabsorption. The neurohormonal and BP responses to changes in posture were also determined in a 30 min orthostatic test. This selected group of patients with NPG had lower 24 h ambulatory BPs (P<0.001), and a more pronounced fall in BP when assuming an upright position (P<0.001) compared with controls. FE(Li) (fractional excretion of lithium) was higher in patients with NPG than controls during the day (36.6+/-21.8 compared with 20.4+/-8.7% respectively; P<0.01; values are means+/-S.D.) as well as during the night (38.8+/-41.9 compared with 19.7+/-10.8% respectively; P<0.02), suggesting a reduced reabsorption of sodium in the proximal tubule. This was compensated for by an increased distal reabsorption of sodium in patients with NPG (P<0.01). These data demonstrate that patients with vasospastic NPG have a high excretion of lithium, suggesting reduced sodium reabsorption in the proximal tubule, in spite of a low BP. The abnormal renal sodium handling might contribute to the maintenance of arterial hypotension and progression of the optic nerve damage in these patients.

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Cerebral blood flow oscillations elicited by inspiratory resistance delays the reporting of orthostatic symptoms with central hypovolemia

We tested the hypothesis that breathing through an inspiratory threshold device (ITD) during progressive central hypovolemia would increase cerebral perfusion and attenuate the reporting of symptoms. Methods: Eight human subjects were exposed to lower body negative pressure (LBNP) until the presence of presyncopal symptoms while breathing through either an active ITD (−7 cmH2O impedance) or a sham ITD (0 cmH2O). Cerebral blood flow velocity (CBFV) was measured continuously via transcranial Doppler and analyzed in both time and frequency domains. Subjects were asked to report any presyncopal symptoms (e.g., dizziness, nausea) at the conclusion of each LBNP exposure. Results: Breathing on the active ITD increased LBNP tolerance time from 2005 ± 104 s to 2254 ± 137 s (p = 0.006). We compared CBFV responses at the time of presyncopal symptoms during the sham ITD trial with those at the same absolute time during the active ITD trial (when there were no symptoms). While there was no difference in mean CBFV at these time points (sham, 49 ± 3 cm/s vs. active, 45 ± 4 cm/s; p = 0.428), total oscillations (sum of high and low frequency spectral power) of cerebral blood flow were higher (p = 0.03) with the active ITD (45.7 ± 10.2 cm/s2) than the sham ITD (22.1 ± 5.4 cm/s2). Conclusion: Greater oscillations around the same absolute level of CBFV are induced by inspiratory resistance and may account for the delay in symptoms with central hypovolemia.

Orthostatic hypotension and cerebral blood flow velocity in the rehabilitation of stroke patients

The objective of this study was to investigate the results of transcranial Doppler monitoring during tilt table tests in stroke patients with and without orthostatic hypotension. In stroke patients without orthostatic hypotension, the mean flow velocity was almost similar in both middle cerebral arteries and was stable during the test. In patients with orthostatic hypotension symptoms, a significant difference was found between the two hemispheres. Mean flow velocity in the damaged middle cerebral artery was lower in the supine position and stayed almost the same at 80 degrees standing. In the non-damaged middle cerebral artery, however, the mean flow velocity was much higher when supine and dropped in the standing position. These findings suggest that the appearance of orthostatic hypotension symptoms may be associated in post-stroke patients with decreased blood velocity in the damaged middle cerebral artery. Those patients are at a high risk of developing syncopal reactions and should be treated on the tilt table with caution, especially at the beginning of the rehabilitation.

Early Abnormalities of Vascular and Cardiac Autonomic Control in Parkinson’s Disease Without Orthostatic Hypotension

Cardiac autonomic abnormalities have been described in Parkinson's disease. Little is known about possible alterations of vascular sympathetic regulatory activity in patients without orthostatic hypotension or symptoms of orthostatic intolerance. Nineteen patients with Parkinson's disease without orthostatic hypotension (PD), 21 with orthostatic hypotension (PDOH), and 20 healthy controls underwent ECG, beat-to-beat arterial pressure, and respiration recordings while recumbent and during a 75 degrees head-up tilt. Spectrum analysis of RR interval and systolic arterial pressure (SAP) variability provided indices of cardiac sympathovagal interaction (low frequency [LF]/high frequency [HF]) to the sinoatrial node and sympathetic vasomotor control (LF(SAP)). Arterial baroreceptor mechanisms were assessed by the spontaneous sequences technique and bivariate spectrum analysis (alpha index). Plasma catecholamines provided the neurohormonal profile. At rest, hemodynamics and spectral markers of autonomic function were similar in PD and control subjects. Norepinephrine was lower in PD and PDOH than in control subjects. In PDOH, SAP was higher, whereas LF/HF ratio and LF(SAP) were lower compared with control subjects. During tilt, SAP was unchanged in PD; however, similar to PDOH, the increase of heart rate, LF/HF ratio, and LF(SAP) was blunted compared with control subjects. Baroreflex indices were unmodified in PD and PDOH compared with control subjects. Initial alterations in both cardiac and vascular sympathetic modulatory activity were found in PD and revealed by a gravitational stimulus. Prompt recognition of sympathetic abnormalities might result in earlier therapeutic intervention, reduced orthostatic intolerance, and increased quality of life.

Parkinson’s Disease

Parkinson’s Disease (PD) is generally considered a movement disorder characterized by loss of dopaminergic neurons in the central nervous system (CNS), most notably in the substantia nigra. The pathogenesis of the neuronal degeneration is not completely understood but is characterized by abnormal protein deposits forming characteristic neuronal inclusions, which are visible by light microscopy of autopsy samples, and termed Lewy bodies. α-Synuclein is one of the proteins found in these inclusions and has attracted interest because mutations of the gene encoding for this protein are found in familiar cases of PD. Most of the disability associated with PD is indeed the result of this CNS defect, and the treatment is aimed at increasing dopamine levels in the CNS, while avoiding as much as possible an increase in the periphery. Less widely recognized is the fact that orthostatic hypotension can occur in PD patients and can become symptomatic and disabling in a significant proportion of patients. The incidence of documented orthostatic hypotension in PD, in community-based studies, ranges from 10% to 40%. Orthostatic hypotension in PD is commonly attributed to the known adverse effects of dopaminergic drugs. However, over the last decade there is growing evidence that peripheral nerves, particularly autonomic neurons, are also involved in PD. Lewy body inclusions, containing α-synuclein, have been found in peripheral autonomic neurons in autopsy cases of otherwise classic PD.1 Microscopically, eosinophilic ubiquitin- and α-synuclein–positive Lewy Bodies and Lewy neurites are not only found in the substantia nigra and locus ceruleus but also are widespread in ganglions cells …

Treatment of post-dialytic orthostatic hypotension with an inflatable abdominal band in hemodialysis patients

The purpose of this study was to ascertain whether abdominal compression with an inflatable abdominal band, a device we developed, improved post-dialytic orthostatic hypotension (OH) in hemodialysis (HD) patients. Twenty-five chronic HD patients with intractable post-dialytic OH were recruited. Post-HD changes in systolic blood pressure (DeltaSBP) in the supine and standing positions were compared in the patients, measured with or without the use of the band. The study showed DeltaSBP after HD without the band was significantly greater than that measured before HD (-36.1+/-18.2 vs -13.1+/-16.8 mm Hg; P<0.0001). DeltaSBP after HD with the band was reduced significantly in comparison to DeltaSBP after HD without the band (-19.4+/-21.2 vs -36.1+/-18.2 mm Hg; P<0.002). Use of the band did not cause an elevation in SBP in the supine position (149.0+/-29.6 vs 155.4+/-25.7 mm Hg); however, it did increase SBP upon standing (129.6+/-27.3 vs 117.2+/-22.6 mm Hg; P<0.05). Eight patients in whom an increase in SBP of 25 mm Hg or more was achieved with the band were classified as responders. Ejection fraction was significantly higher (76.4+/-11.1 vs 61.9+/-13.6%; P<0.02) and atrial natriuretic peptide concentration significantly lower (27.9+/-22.0 vs 68.9+/-47.5 pg/ml; P<0.02) in responders than in non-responders. We conclude that the abdominal band was effective for overcoming post-dialytic OH, without elevating supine SBP in some patients.

Increased impedance to inspiration ameliorates hemodynamic changes associated with movement to upright posture in orthostatic hypotension: A randomized blinded pilot study

Movement to upright posture may result in marked drop of blood pressure with susceptibility to injury from syncope and falls in patients with orthostatic hypotension. The purpose of this study was to determine if increasing negative intrathoracic pressure by using an inspiratory impedance threshold device before change of posture diminishes blood pressure fall by enhancing venous return. Eighteen healthy subjects and 22 orthostatic hypotension patients were randomized to either an active (impedance 7 cmH2O) or sham (no inspiratory impedance) impedance threshold device. Arterial blood pressure, heart rate, and estimated stroke volume and total peripheral resistance were recorded in the supine and upright postures using a noninvasive finger arterial blood pressure monitor. After a rest period, the alternate impedance threshold device (sham or active) was tested in each individual. Compared with the sham impedance threshold device test, the active impedance threshold device resulted in significant reduction in the magnitude of upright posture-induced fall in blood pressure and a greater increase of total peripheral resistance after standing in both healthy subjects and orthostatic hypotension patients. Stroke volume was not measurably altered. Among all subjects who exhibited a postural blood pressure drop >10 mmHg on the day of study, active impedance threshold device treatment consistently blunted blood pressure fall during the initial 100 seconds after standing (<0.04). Induced orthostatic symptoms were less severe with the active impedance threshold device both at onset of upright posture and during 30 seconds of standing. Enhancing impedance to inspiration may prove useful as adjunctive therapy for diminishing symptoms associated with movement to upright posture in individuals with orthostatic hypotension.

Acetylcholinesterase Inhibition in Patients With Orthostatic Intolerance

The efficacy of current therapeutic measures in orthostatic intolerance (OI) varies among patients and is oftentimes unsatisfactory. New approaches to alleviate symptoms of OI are therefore clearly needed. Recent reports have demonstrated that acetylcholinesterase inhibition is effective in the treatment of orthostatic hypotension with the presumed mechanism of enhancing sympathetic ganglionic transmission. Based on the hypothesis that acetylcholinesterase inhibition, by improving the safety factor of cholinergic transmission, will result in enhanced vascular adrenergic tone and a vagal shift in cardiac sympathovagal balance, we evaluated the role of acetylcholinesterase inhibition in the treatment of patients with OI. We monitored heart rate (HR), blood pressure, and indexes for cardiac output, end-diastolic volume, and systemic resistance continuously in 18 patients with OI during supine rest and during 5 minutes of 70 degrees head-up tilt before and 1 hour after oral administration of 60 mg pyridostigmine. Plasma catecholamines and baroreflex sensitivity were determined for the supine and upright position before and after medication. Patients scored orthostatic symptoms for both tilt studies. The excessive HR response to orthostatic stress was significantly blunted after pyridostigmine administration. HR was significantly lower in the supine and more so in the upright position. Baroreflex sensitivity in the upright position was significantly higher after pyridostigmine. Norepinephrine was increased in both supine and upright position. These changes were associated with significant improvement of orthostatic symptoms. We conclude that pyridostigmine improves orthostatic tolerance in patients with OI. Our findings support the suggested mechanisms of enhanced sympathetic ganglionic neurotransmission and a vagal shift in cardiac sympathovagal balance. Acetylcholinesterase inhibition could be a new useful concept in the treatment of OI.