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• W3085872441 abstract "Abstract Objective 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 11 C‐methylreboxetine ( 11 C‐MRB), a selective ligand for the cell membrane norepinephrine transporter, to quantify interventricular septal myocardial noradrenergic innervation and using 18 F‐dopamine ( 18 F‐DA) to assess intraneuronal vesicular storage in the same subjects. Methods Seven comprehensively tested PAF patients and 11 controls underwent 11 C‐MRB PET scanning for 45 minutes (dynamic 5X1’, 3X5’, 1X10’, static 15 minutes) and 18 F‐DA scanning for 30 minutes (same dynamic imaging sequence) after 3‐minute infusions of the tracers on separate days. Results In the PAF group septal 11 C‐MRB‐derived radioactivity in the static frame was decreased by 26.7% from control (p = 0.012). After adjustment for nonspecific binding of 11 C‐MRB, the PAF group had a 41.1% mean decrease in myocardial 11 C‐MRB‐derived radioactivity (p = 0.015). The PAF patients had five times faster postinfusion loss of 18 F‐DA‐derived radioactivity (70 ± 3% vs. 14 ± 8% by 30 minutes, p < 0.0001). At all time points after infusion of 18 F‐DA and 11 C‐MRB mean 18 F/ 11 C ratios in septal myocardium were lower in the PAF than control group. Interpretation PAF entails moderately decreased cardiac sympathetic innervation and a substantial vesicular storage defect in residual nerves." @default.
• W3085872441 created "2020-09-21" @default.
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• W3085872441 date "2020-09-10" @default.
• W3085872441 modified "2023-09-25" @default.
• W3085872441 title "Cardiac sympathetic innervation and vesicular storage in pure autonomic failure" @default.
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• W3085872441 doi "https://doi.org/10.1002/acn3.51184" @default.
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