The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
The Neuropathic Postural Tachycardia Syndrome
Open accessAbstract
BACKGROUND: The postural tachycardia syndrome is a common disorder that is characterized by chronic orthostatic symptoms and a dramatic increase in heart rate on standing, but that does not involve orthostatic hypotension. Several lines of evidence indicate that this disorder may result from sympathetic denervation of the legs. METHODS: We measured norepinephrine spillover (the rate of entry of norepinephrine into the venous circulation) in the arms and legs both before and in response to exposure to three stimuli (the cold pressor test, sodium nitroprusside infusion, and tyramine infusion) in 10 patients with the postural tachycardia syndrome and in 8 age- and sex-matched normal subjects. RESULTS: At base line, the mean (+/-SD) plasma norepinephrine concentration in the femoral vein was lower in the patients with the postural tachycardia syndrome than in the normal subjects (135+/-30 vs. 215+/-55 pg per milliliter [0.80+/-0.18 vs. 1.27+/-0.32 nmol per liter], P=0.001). Norepinephrine spillover in the arms increased to a similar extent in the two groups in response to each of the three stimuli, but the increases in the legs were smaller in the patients with the postural tachycardia syndrome than in the normal subjects (0.001+/-0.09 vs. 0.12+/-0.12 ng per minute per deciliter of tissue [0.006+/-0.53 vs. 0.71+/-0.71 nmol per minute per deciliter] with the cold pressor test, P=0.02; 0.02+/-0.07 vs. 0.23+/-0.17 ng per minute per deciliter [0.12+/-0.41 vs. 1.36+/-1.00 nmol per minute per deciliter] with nitroprusside infusion, P=0.01; and 0.008+/-0.09 vs. 0.19+/-0.25 ng per minute per deciliter [0.05+/-0.53 vs. 1.12+/-1.47 nmol per minute per deciliter] with tyramine infusion, P=0.04). CONCLUSIONS: The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.
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“It is believed that impaired sympathetic tone (as measured by norepinephrine spillover) reduces venoconstriction, leading to venous pooling in the lower limbs and splanchnic beds.24”
From 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope (2015) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Features described in subgroups of patients include increased sympathetic nervous system tone (i.e., hyperadrenergic POTS),17 partial peripheral sympathetic denervation leading to relative central hypovolemia (i.e., neuropathic POTS)27 and low blood volume (i.e., absolute hypovolemia),28 which may drive some of the other hemodynamic findings.”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [27]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“More commonly proposed causes include partial peripheral neuropathy (“neuropathic POTS”),19 a deficit in blood volume, abnormalities in the renin-angiotensin-aldosterone system (RAAS)20, physical deconditioning,10 autoantibodies targeting peripheral adrenergic receptors21 and a hyperadrenergic state resulting from central activation of the sympathetic nervous system (“HyperPOTS”).”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [19]
In the citing paper
“Neuropathic POTS was first described when activation of the sympathetic nervous system increased norepinephrine spillover in the lower limbs of some patients to a lesser extent than in healthy controls, despite similar responses in the arms [42].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [42]
In the citing paper
“Jacob et al. (18) demonstrated significantly impaired sympathetic nervous system activity in the lower extremities of POTS patients.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [18]
In the citing paper
“Amounts of norepinephrine released at sympathetic nervous system synapses in the lower extremities in response to a cold pressor test, a nitroprusside infusion, and a tyramine infusion were markedly lower in POTS patients than in healthy controls.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [18]
In the citing paper
“In contrast, the amounts of norepinephrine released in the upper extremities in response to the same stimuli were no different between POTS patients and healthy controls.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [18]
In the citing paper
“approximately 50% of POTS patients evaluated at tertiary care centers exhibit a neuropathic phenotype associated with partial sympathetic denervation, usually due to a distal small fiber neuropathy producing sympathetic denervation of the lower limbs”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Jacob et al., 2000
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Citations
Cites
Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions
Esler, M., Jennings, G., Lambert, G., Meredith, I., Horne, M., & Eisenhofer, G. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.4.963 · Cited by 794
Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency
Shannon, J. R., Flattem, N. L., Jordan, J., Jacob, G., Black, B. K., Biaggioni, I., Blakely, R. D., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002243420803 · Cited by 594
Self-citationIdiopathic postural orthostatic tachycardia syndrome: An attenuated form of acute pandysautonomia?
Schondorf, R., & Low, P. A. (1993) · Neurology · doi:10.1212/wnl.43.1_part_1.132 · Cited by 548
Quantitative sudomotor axon reflex test in normal and neuropathic subjects
Low, P. A., Caskey, P. E., Tuck, R. R., Fealey, R. D., & Dyck, P. J. B. (1983) · Annals of Neurology · doi:10.1002/ana.410140513 · Cited by 491
Exercise training-induced hypervolemia: role of plasma albumin, renin, and vasopressin
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Goldstein, D. S., Eisenhofer, G., Stull, R., Folio, C. J., Keiser, H. R., & Kopin, I. J. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113298 · Cited by 245
Hague, K., Lento, P., Morgello, S., Caro, S., & Kaufmann, H. (1997) · Acta Neuropathologica · doi:10.1007/s004010050693 · Cited by 209
Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia
Jacob, G., Shannon, J. R., Black, B., Biaggioni, I., Mosqueda-Garcia, R., Robertson, R. M., & Robertson, D. (1997) · Circulation · doi:10.1161/01.cir.96.2.575 · Cited by 206
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Frohlich, E. D. (1969) · Archives of Internal Medicine · doi:10.1001/archinte.123.1.1 · Cited by 171
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Cited by
Sorted by citations
Sheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013
“It is believed that impaired sympathetic tone (as measured by norepinephrine spillover) reduces venoconstriction, leading to venous pooling in the lower limbs and splanchnic beds.(24) This neuropathic manifestation of POTS requires a high cardiac output to compensate for reduced splanchnic and peripheral resistance an…”
BackgroundBlomström‐Lundqvist, C., Scheinman, M. M., Aliot, E., Alpert, J. S., Calkins, H. G., Camm, A. J., Campbell, W. B., Haines, D. E., Kück, K., Lerman, B. B., et al. (2003) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.08.013 · Cited by 684
Dysautonomia in the joint hypermobility syndrome
Gazit, Y., Nahir, A. M., Grahame, R., & Jacob, G. (2003) · The American Journal of Medicine · doi:10.1016/s0002-9343(03)00235-3 · Cited by 390
Self-citationPostural orthostatic tachycardia syndrome: the Mayo clinic experience
Thieben, M. J., Sandroni, P., Sletten, D. M., Benrud-Larson, L. M., Fealey, R. D., Vernino, S., Low, P. A., Lennon, V. A., & Shen, W.-K. (2007) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)61027-6 · Cited by 516
Postural tachycardia syndrome: a heterogeneous and multifactorial disorder
Benarroch, E. E. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2012.08.013 · Cited by 370
Metadata
- Authors
- Jacob, G., Costa, F., Shannon, J. R., Robertson, R. M., Wathen, M., Stein, M., Biaggioni, I., Ertl, A., Black, B., & Robertson, D.
- Affiliations
- Vanderbilt University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-10-05
- Volume
- 343
- Issue
- 14
- Pages
- 1008-1014
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2323218437
- Semantic Scholar
- 407efaeed6a32a863bb8fc0e44db81b5b8d4944b
- Cited by
- 398
- References
- 40
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 16 · 2021: 13 · 2020: 19 · 2019: 9 · 2018: 14 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 21 · 2013: 16 · 2012: 16
- FWCI
- 20.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- Vanderbilt University
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL56693, P01HL056693)
- National Center for Research Resources (RR00095)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- postural orthostatic tachycardia syndrome, sympathetic denervation, norepinephrine spillover, plasma norepinephrine, orthostatic intolerance, cold pressor test, sodium nitroprusside, tyramine, sympathetic nervous system, autonomic dysfunction
- MeSH terms
- Adult, Arm, Autonomic Nervous System Diseases, Blood Pressure, Cold Temperature, Female, Femoral Vein, Heart Rate, Humans, Leg, Male, Nitroprusside, Norepinephrine, Posture, Reference Values, Sympathetic Nervous System, Tachycardia, Tyramine, Case-Control Studies
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