TY - JOUR
T1 - Cardiac sympathetic hypo-innervation in familial dysautonomia
AU - Goldstein, David S.
AU - Eldadah, Basil
AU - Sharabi, Yehonatan
AU - Axelrod, Felicia B.
PY - 2008/6
Y1 - 2008/6
N2 - 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-[ 18F]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-[18F]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-[18F]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-[18F]fluorodopamine-derived radioactivity. Conclusions: FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[18F]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals.
AB - 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-[ 18F]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-[18F]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-[18F]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-[18F]fluorodopamine-derived radioactivity. Conclusions: FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[18F]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals.
KW - Familial dysautonomia
KW - Fluorodopamine
KW - Norepinephrine
KW - Positron emission tomography
KW - Sympathetic nervous system
UR - http://www.scopus.com/inward/record.url?scp=44749084587&partnerID=8YFLogxK
U2 - 10.1007/s10286-008-0464-1
DO - 10.1007/s10286-008-0464-1
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C2 - 18498023
AN - SCOPUS:44749084587
VL - 18
SP - 115
EP - 119
JO - Clinical Autonomic Research
JF - Clinical Autonomic Research
SN - 0959-9851
IS - 3
ER -