Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes

David S. Goldstein, Courtney Holmes, Steven M. Frank, Raghuveer Dendi, Richard O. Cannon, Yehonatan Sharabi, Murray D. Esler, Graeme Eisenhofer

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2358-2365
Number of pages8
Issue number18
StatePublished - 29 Oct 2002
Externally publishedYes


  • Catecholamines
  • Dysautonomia
  • Nervous system, sympathetic
  • Norepinephrine


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