title: Cardiac sympathetic hypo-innervation in familial dysautonomia.
abstract: OBJECTIVE
  Familial dysautonomia (FD) involves incomplete development of the sympathetic nervous system. Whether such loss extends to sympathetic innervation of the heart has been unknown. This study used 6-[(18)F]fluorodopamine neuroimaging to assess cardiac sympathetic innervation and function in FD.
  
  
  METHODS
  Six adult FD patients underwent thoracic PET scanning for 30 minutes after i.v. 6-[(18)F]fluorodopamine injection, as did healthy volunteers without (N = 21) or with (N = 10) pre-treatment by desipramine, which interferes with neuronal uptake and thereby simulates effects of noradrenergic denervation. Effective rate constants for uptake and loss were calculated using a single compartment pharmacokinetic model.
  
  
  RESULTS
  FD patients had decreased uptake and accelerated loss of 6-[(18)F]fluorodopamine-derived radioactivity in the interventricular myocardial septum (P = 0.009, P = 0.05) and ventricular free wall (P = 0.007, P < 0.001), compared to untreated controls. Desipramine-treated subjects had decreased uptake but normal loss of 6-[(18)F]fluorodopamine-derived radioactivity.
  
  
  CONCLUSIONS
  FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[(18)F]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals.
authors.affiliation: Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, NIH, 10 Center Drive MSC-1620, Building 10 Room 6N252, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: Basil
authors.initials: B
authors.lastname: Eldadah
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
authors.forename: Felicia B
authors.initials: FB
authors.lastname: Axelrod
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D016022:Case-Control Studies; D002395:Catecholamines / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives; D004402:Dysautonomia, Familial / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine; D049268:Positron-Emission Tomography; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002395:Catecholamines; D005462:Fluorine Radioisotopes; C029253:6-fluorodopamine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine