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Cited by 230Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlCardiovascular and exercise physiology

Chronic Orthostatic Intolerance: A Disorder With Discordant Cardiac and Vascular Sympathetic Control

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Furlan, Raffaello, Jacob, Giris, Snell, Marie, Robertson, David, Porta, Alberto, Harris, Paul, Mosqueda-Garcia, Rogelio·1998·Circulation
DOI 10.1161/01.cir.98.20.2154
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Abstract

Background —Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). Methods and Results —In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75° tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LF SAP ). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index α, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LF SAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced α similarly in both groups. Conclusions —COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

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  • A deficiency of the norepinephrine transporter may explain several clinical findings in patients with orthostatic intolerance.

    “A deficiency of the norepinephrine transporter may explain several of the clinical findings in patients with this disorder: the high heart rate in the supine position, the high plasma concentration of norepinephrine in association with the relatively low plasma concentration of dihydroxyphenylglycol, the impaired response of norepinephrine to tyramine, 13 the reduced systemic clearance of norepine”

    From Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency (2000) · cites this paper as [27]

    The Autonomic Control section reports elevated supine norepinephrine and tachycardia, but proposes a possible central nervous system abnormality rather than a norepinephrine-transporter deficiency. Searches for transporter deficiency, tyramine, and dihydroxyphenylglycol found no passage in our copy addressing the claimed explanation. (LLM, conf=0.76)

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  • Plasma norepinephrine is sometimes higher at supine rest and increases more with head-up tilt in POTS.

    “A spectral analysis index of sympathetic function and plasma norepinephrine are sometimes higher at supine rest and increase more with HUT in POTS [53;52].”

    From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [52]

  • Resting sympathetic nerve activity measured by microneurography is elevated in POTS.

    “Resting sympathetic nerve activity, measured by microneurography, is elevated.”

    From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [52]

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1 of the 41 references couldn’t be matched to a known paper.

Research works printed but not linked: 8

  1. Fouad FM, Tadena-Thome L, Bravo EL, Tarazi RC. Idiopathic hypo- volemia. Arch Intern Med. 1986;104:298 -303.
  2. Streeten DHP. Pathogenesis of hyperadrenergic orthostatic hypotension. J Clin Invest. 1990;86:1582-1588.
  3. Hoeldtke RD, Dworkin GE, Gaspar SR, Israel BC. Sympathotonic ortho- static hypotension: a report of four cases. Neurology. 1989;39:34 -40.
  4. Mosqueda-Garcia R. Microneurography in neurological research. Am Acad Neurol. 1996;2:4 -5.
  5. Vallbo AB, Hagbarth KE, Torebjork HE, Wallin BG. Somatosensory, proprioceptive and sympathetic activity from peripheral nerves. Physiol Rev. 1979;59:919 -957.
  6. Smyth HS, Sleight P, Pickering GW. A quantitative method of assessing baroreflex sensitivity. Circ Res. 1969;24:109 -121.
  7. Khurana RK. Orthostatic intolerance and orthostatic tachycardia: hetero- geneous disorder. Clin Autonom Res. 1995;5:12-18.
  8. Jacob G, Robertson RM, Costa F, Wathen MS, Stein M, Black BK, Biaggioni I, Robertson D. The local norepinephrine spillover in arms and legs of patients with idiopathic orthostatic intolerance: evidence of partial dysautonomia. Clin Auton Res. 1997;7:235. Abstract.

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Authors
Furlan, R., Jacob, G., Snell, M., Robertson, D., Porta, A., Harris, P., & Mosqueda-Garcia, R.
Affiliations
  • Vanderbilt University (US)
  • From the Syncope Service in the Autonomic Dysfunction Unit (M.S., D.R., R.M.-G.) and Division of Clinical Pharmacology (R.F., G.J., D.R., P.H., R.M.-G.), Department of Medicine (D.R., R.M.-G.), Vanderbilt University Medical Center, Nashville, Tenn, and Dipartimento di Bioingegneria, Politecnico di Milano, Milan, Italy (A.P.).
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1998-11-17
Volume
98
Issue
20
Pages
2154-2159
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.98.20.2154
OpenAlex
W2159657770
Cited by
229
References
41
Citations by year
2026: 6 · 2025: 3 · 2024: 12 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 10 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 5
FWCI
12.95
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
autonomic dysfunction, baroreflex sensitivity, muscle sympathetic nerve activity, heart rate variability, blood pressure variability, tilt table, central venous pressure
MeSH terms
Adult, Chronic Disease, Female, Hemodynamics, Humans, Male, Posture, Pressoreceptors, Reflex, Sympathetic Nervous System, Tachycardia

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