Leg pain in neuropathic postural tachycardia syndrome is associated with altered muscle membrane properties

Abstract Purpose In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects. Methods In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed. Results In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects. Conclusions This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome.

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Orthostatic leg pain in neuropathic postural tachycardia syndrome: what does muscle excitability have to do with it?

Clinical Autonomic Research ◽

10.1007/s10286-021-00840-3 ◽

2021 ◽

Author(s):

Amy C. Arnold ◽

Judith Navarro-Otano

Keyword(s):

Leg Pain ◽

Postural Tachycardia Syndrome ◽

Postural Tachycardia ◽

Muscle Excitability

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Diurnal variability in orthostatic tachycardia: implications for the postural tachycardia syndrome

Clinical Science ◽

10.1042/cs20110077 ◽

2011 ◽

Vol 122 (1) ◽

pp. 25-31 ◽

Cited By ~ 28

Author(s):

Jordan A. Brewster ◽

Emily M. Garland ◽

Italo Biaggioni ◽

Bonnie K. Black ◽

John F. Ling ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Supine Position ◽

Healthy Subjects ◽

Postural Tachycardia Syndrome ◽

Healthy Controls ◽

Diurnal Variability ◽

Postural Tachycardia ◽

Clinical Research Center

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.

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Abstract P187: Nitric Oxide Function in Postural Tachycardia Syndrome During High and Low Sodium Diets

Hypertension ◽

10.1161/hyp.70.suppl_1.p187 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Jorge E Celedonio ◽

Victor C Nwazue ◽

Emily M Garland ◽

Cyndya A Shibao ◽

Luis E Okamoto ◽

...

Keyword(s):

Nitric Oxide ◽

Healthy Subjects ◽

High Salt ◽

Postural Tachycardia Syndrome ◽

Brachial Artery Diameter ◽

High Salt Diet ◽

Salt Diet ◽

Postural Tachycardia ◽

Resistance Vessels ◽

Low Salt

Background: Postural tachycardia syndrome (POTS) is characterized by an increase in sympathetic activity, with an exaggerated rise in heart rate upon standing and symptoms of cerebral hypoperfusion. Endothelial/Nitric Oxide (NO) dysfunction might be involved in POTS pathophysiology. As part of the non-pharmacologic treatment of POTS, a high sodium diet is often recommended to increase plasma volume. We assessed endothelial/NO function in conduit vessels (using flow-mediated dilation, FMD) and resistance vessels (using finger pulse arterial tonometry, PAT) in POTS patients during high and low salt diets. Methods: In 14 female POTS patients (34±9 years, BMI 23±3 kg/m 2 ) and 13 matched healthy control subjects (29±4 years, BMI 24±3 kg/m 2 ), we evaluated the time course responses to FMD and PAT. Subjects were randomly assigned to either high salt diet (300mEq/day) or low salt diet (10mEq/day) for 6 days and crossed over to the other arm after 1 month. The areas under the curve for brachial artery diameter by FMD and finger artery dilation by PAT were compared between interventions and groups. Results: No differences in NO function in a conduit artery were seen. In contrast, in resistance vessels, high salt diet increased vasodilation in both POTS and healthy subjects (figure). In addition, POTS patients have greater vasodilation than healthy subjects during both low and high salt diets (p=0.036 and 0.033 for high and salt diets respectively). Conclusions: POTS patients may have an exaggerated NO response to reactive hyperemia in resistance vessels, but not in conductance vessels. This excessive vasodilation could contribute to POTS symptoms on standing.

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Nitric Oxide and Regulation of Heart Rate in Patients With Postural Tachycardia Syndrome and Healthy Subjects

Hypertension ◽

10.1161/hypertensionaha.111.00203 ◽

2013 ◽

Vol 61 (2) ◽

pp. 376-381 ◽

Cited By ~ 8

Author(s):

Alfredo Gamboa ◽

Luis E. Okamoto ◽

Satish R. Raj ◽

André Diedrich ◽

Cyndya A. Shibao ◽

...

Keyword(s):

Nitric Oxide ◽

Heart Rate ◽

Healthy Subjects ◽

Postural Tachycardia Syndrome ◽

Postural Tachycardia

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Characteristics of Heart Rate Reduction with Resumption of Supine Position in the Postural Tachycardia Syndrome: Factors Influencing Recovery

The Open Cardiovascular Medicine Journal ◽

10.2174/1874192401307010036 ◽

2013 ◽

Vol 7 (1) ◽

pp. 36-39 ◽

Cited By ~ 2

Author(s):

Kenneth A Mayuga ◽

Christopher E Gaw ◽

Curtis Tatsuoka ◽

Fetnat Fouad-Tarazi

Keyword(s):

Heart Rate ◽

Supine Position ◽

Autonomic Function ◽

Postural Tachycardia Syndrome ◽

Postural Orthostatic Tachycardia Syndrome ◽

Rate Reduction ◽

Postural Tachycardia ◽

Younger Age ◽

Head Up Tilt ◽

Blood Pressures

Objectives: Postural orthostatic tachycardia syndrome (POTS), a heart rate (HR) rise with upright positioning, is dependent on autonomic influences. HR recovery (HR decrease after exercise cessation) is a measure of autonomic function. Characteristics of HR reduction during supine Recovery after head-up Tilt in POTS patients have not been elucidated. Methods: 113 subjects (mean age 41.7 years, 86 female), diagnosed with POTS on head-up Tilt were analyzed. HR’s were recorded during baseline supine position, 70-degree Tilt, and 20 sec, 1 min and 2 min of supine Recovery. Percent HR reduction during Recovery was calculated. Results: Baseline HR was 68.7±13.4 bpm. Maximum HR during Tilt was 109±16.9 bpm. Mean HR was 84.2±20 bpm at 20 sec, 78.5±18.9 bpm at 1-min, and 77.1±18.3 bpm at 2 min of Recovery. Younger age and slower baseline HR were associated with greater HR reductions at 20 sec (p=0.006, p=0.000, respectively). Younger age, slower baseline HR and less time to achieve POTS were associated with greater HR reductions at 1 min (p=0.025, p=0.000, p=0.000, respectively) and at 2 min (p=0.004, p=0.000, p=0.000, respectively). Gender and baseline blood pressures were not significant. Conclusions: In POTS patients, HR quickly decreases upon resuming supine position. Younger age, slower baseline HR and less time to achieve POTS were associated with greater HR reductions during supine Recovery. Further study is needed to determine mechanisms, as well as analyze differences in symptoms or prognosis.

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P319 Differences in adrenergic components of baroreflex response to valsalva maneuver in patients with postural tachycardia syndrome and healthy subjects

Clinical Neurophysiology ◽

10.1016/j.clinph.2017.07.327 ◽

2017 ◽

Vol 128 (9) ◽

pp. e281

Author(s):

Dunja Pucic ◽

Bojana Nevajdic ◽

Tomislav Mutak ◽

Luka Crnosija ◽

Magdalena Krbot Skoric ◽

...

Keyword(s):

Healthy Subjects ◽

Valsalva Maneuver ◽

Postural Tachycardia Syndrome ◽

Postural Tachycardia

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Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00784.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. H665-H673 ◽

Cited By ~ 65

Author(s):

Julian M. Stewart ◽

Marvin S. Medow ◽

June L. Glover ◽

Leslie D. Montgomery

Keyword(s):

Blood Flow ◽

Blood Volume ◽

Supine Position ◽

High Flow ◽

Splanchnic Blood Flow ◽

Low Flow ◽

Postural Tachycardia Syndrome ◽

Lower Body ◽

Normal Flow ◽

Postural Tachycardia

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising “normal-flow POTS” patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20°, 35°, and 70°. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.

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Regional blood volume and peripheral blood flow in postural tachycardia syndrome

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00086.2004 ◽

2004 ◽

Vol 287 (3) ◽

pp. H1319-H1327 ◽

Cited By ~ 53

Author(s):

Julian M. Stewart ◽

Leslie D. Montgomery

Keyword(s):

Blood Flow ◽

Blood Volume ◽

Supine Position ◽

Peripheral Blood ◽

Postural Tachycardia Syndrome ◽

Peripheral Blood Flow ◽

Control Subjects ◽

Postural Tachycardia ◽

Regional Blood Volume ◽

Upright Tilt

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.

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