Cardiac sympathetic hypo-innervation in familial dysautonomia
- 102 Downloads
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.
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.
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.
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.
Keywordsfamilial dysautonomia fluorodopamine sympathetic nervous system positron emission tomography norepinephrine
This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke.
- 3.Close P, Hawkes N, Cornez I, Creppe C, Lambert CA, Rogister B, Siebenlist U, Merville MP, Slaugenhaupt SA, Bours V, Svejstrup JQ, Chariot A (2006) Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia. Mol Cell 22:521–531PubMedCrossRefGoogle Scholar
- 7.Goldstein DS, Eisenhofer G, Dunn BB, Armando I, Lenders J, Grossman E, Holmes C, Kirk KL, Bacharach S, Adams R, Herscovitch P, Kopin IJ (1993) Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans. J Am Coll Cardiol 22:1961–1971PubMedCrossRefGoogle Scholar
- 8.Goldstein DS, Grossman E, Tamrat M, Chang PC, Eisenhofer G, Bacher J, Kirk KL, Bacharach S, Kopin IJ (1991) Positron emission imaging of cardiac sympathetic innervation and function using 18F-6-fluorodopamine: effects of chemical sympathectomy by 6-hydroxydopamine. J Hypertens 9:417–423PubMedCrossRefGoogle Scholar
- 18.Rotstein A, Charrow J, Deal BJ (2007) Documented transient third-degree atrioventricular block and asystole in a child with familial dysautonomia. Pediatr CardiolGoogle Scholar
- 19.Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF (2001) Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet 68:598–605PubMedCrossRefGoogle Scholar