{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:38:12Z","timestamp":1783391892924,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Division or Intramural Research, NINDS, NIH"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Pure autonomic failure (PAF) is a rare disease characterized by neurogenic orthostatic hypotension (nOH), absence of signs of central neurodegeneration, and profound deficiency of the sympathetic neurotransmitter norepinephrine. Reports have disagreed about mechanisms of the noradrenergic lesion. Neuropathological studies have highlighted denervation, while functional studies have emphasized deficient vesicular sequestration of cytoplasmic catecholamines in extant neurons. We examined both aspects by a combined positron emission tomographic (PET) neuroimaging approach using <jats:sup>11<\/jats:sup>C\u2010methylreboxetine (<jats:sup>11<\/jats:sup>C\u2010MRB), a selective ligand for the cell membrane norepinephrine transporter, to quantify interventricular septal myocardial noradrenergic innervation and using <jats:sup>18<\/jats:sup>F\u2010dopamine (<jats:sup>18<\/jats:sup>F\u2010DA) to assess intraneuronal vesicular storage in the same subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seven comprehensively tested PAF patients and 11 controls underwent <jats:sup>11<\/jats:sup>C\u2010MRB PET scanning for 45\u00a0minutes (dynamic 5X1\u2019, 3X5\u2019, 1X10\u2019, static 15\u00a0minutes) and <jats:sup>18<\/jats:sup>F\u2010DA scanning for 30\u00a0minutes (same dynamic imaging sequence) after 3\u2010minute infusions of the tracers on separate days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the PAF group septal <jats:sup>11<\/jats:sup>C\u2010MRB\u2010derived radioactivity in the static frame was decreased by 26.7% from control (p\u00a0=\u00a00.012). After adjustment for nonspecific binding of <jats:sup>11<\/jats:sup>C\u2010MRB, the PAF group had a 41.1% mean decrease in myocardial <jats:sup>11<\/jats:sup>C\u2010MRB\u2010derived radioactivity (p\u00a0=\u00a00.015). The PAF patients had five times faster postinfusion loss of <jats:sup>18<\/jats:sup>F\u2010DA\u2010derived radioactivity (70\u00a0\u00b1\u00a03% vs. 14\u00a0\u00b1\u00a08% by 30\u00a0minutes, p\u00a0&lt;\u00a00.0001). At all time points after infusion of <jats:sup>18<\/jats:sup>F\u2010DA and <jats:sup>11<\/jats:sup>C\u2010MRB mean <jats:sup>18<\/jats:sup>F\/<jats:sup>11<\/jats:sup>C ratios in septal myocardium were lower in the PAF than control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>PAF entails moderately decreased cardiac sympathetic innervation and a substantial vesicular storage defect in residual nerves.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51184","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T07:07:46Z","timestamp":1600931266000},"page":"1908-1918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cardiac sympathetic innervation and vesicular storage in pure autonomic failure"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":false,"given":"David 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