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Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure

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Abstract

Primary autonomic failure is a heterogenous group of diseases with evidence for lesions in both the central and peripheral elements of the autonomic nervous system. We determined the extent of peripheral sympathetic dysfunction in six patients with primary autonomic failure without clinical evidence of central nervous system involvement (pure autonomic failure) using biochemical methods for studying regional noradrenaline spillover and removal. The results were compared with those from 14 agematched normal subjects, seven of whom were studied before and after pharmacological neuronal uptakeblockade with desipramine. Total, cardiac and renal noradrenaline spillover to plasma were 78%, 98% and 66% lower respectively in pure autonomic failure than in normal subjects (p < 0.001). Total noradrenaline plasma clearance was 20% lower in pure autonomic failure (p < 0.005) than in normal subjects and similar to the level observed in normal subjects following neuronal noradrenaline uptake-blockade with desipramine, mean transcardiac extraction of tritiated noradrenaline was 74% in normal subjects and 20% in pure autonomic failure, identical to the value post-desipramine in normal subjects. Cardiac spillover of the noradrenaline precursor, dihydroxyphenylalanine, and the primary intra-neuronal metabolite dihydroxyphenylglycol, were 78% and 94% lower respectively in pure autonomic failure than in normal subjects (p < 0.001). These data indicate a marked reduction in the apparent release rate and neuronal uptake of noradrenaline in the hearts of patients with pure autonomic failure, and provide biochemical evidence of almost total postganglionic sympathetic denervation in this condition.

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Authors and Affiliations

  1. Alfred and Baker Medical Unit, Baker Medical Research Institute, Commercial Road, Prahran, 3181, Melbourne, Australia

    Ian T. Meredith (MBBS), Murray D. Esler (MBBS), Helen S. Cox BSc, Gavin W. Lambert BSc, Garry L. Jennings MD & Graeme Eisenhofer PhD

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  1. Ian T. Meredith
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  2. Murray D. Esler
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  3. Helen S. Cox BSc
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  4. Gavin W. Lambert BSc
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  5. Garry L. Jennings MD
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  6. Graeme Eisenhofer PhD
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Meredith, I.T., Esler, M.D., Cox, H.S. et al. Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure. Clinical Autonomic Research 1, 187–194 (1991). https://doi.org/10.1007/BF01824986

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  • DOI: https://doi.org/10.1007/BF01824986

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