Published Online
on October 7, 2002

A more recent version of this article appeared on October 29, 2002

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Submitted on June 17, 2002
Revised on August 16, 2002
Accepted on August 16, 2002

Cardiac Sympathetic Dysautonomia in Chronic Orthostatic Intolerance Syndromes

David S. Goldstein MD, PhD^*, Courtney Holmes CMT, Steven M. Frank MD, Raghuveer Dendi MD, Richard O. Cannon III MD, Yehonatan Sharabi MD, Murray D. Esler MBBS, PhD, and Graeme Eisenhofer PhD

From Clinical Neurocardiology Section, NINDS, NIH; Department of Anesthesiology and Critical Care Medicine (S.M.F.), The Johns Hopkins Medical Institutions, Baltimore, Md; Cardiology Branch (R.O.C.), NHLBI; and Baker Medical Research Institute (M.D.E.), Victoria, Australia.

^* To whom correspondence should be addressed. E-mail: goldsteind{at}ninds.nih.gov.

Background—In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear.

Methods and Results—Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating ³H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[¹⁸F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171±30 pmol/min, N=16) was higher and in NCS (62±9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102±9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106±18 pmol/min, N=11). Both patient groups had normal cardiac extraction of ³H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity.

Conclusions—POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.

Key words: catecholamines • nervous system, sympathetic • norepinephrine • dysautonomia

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