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-[F-18]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-[F-18]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-[F-18]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-[F-18]fluorodopamine-derived radioactivity. Conclusions FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[F-18]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals.