Cardiac sympathetic hypo-innervation in familial dysautonomia.
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.
Goldstein
David S
DS
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
Eldadah
Basil
B
Sharabi
Yehonatan
Y
Axelrod
Felicia B
FB
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*
D000929:Antidepressive Agents, Tricyclic; D002395:Catecholamines; D005462:Fluorine Radioisotopes; C029253:6-fluorodopamine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine