title: Cardiac sympathetic denervation in Parkinson disease.
abstract: BACKGROUND
  In Parkinson disease, orthostatic hypotension can result from L-dopa treatment or from sympathetic neurocirculatory failure. The latter is detected by abnormal blood pressure responses to the Valsalva maneuver and can be associated with loss of functional cardiac sympathetic nerve terminals.
  
  
  OBJECTIVE
  To determine the frequency of cardiac sympathetic denervation in Parkinson disease, with or without sympathetic neurocirculatory failure, and its association with disease duration, severity, and L-dopa treatment
  
  
  METHODS
  Intergroup comparisons in resting patients.
  
  
  METHODS
  National Institutes of Health Clinical Center, Bethesda, Maryland.
  
  
  METHODS
  29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers.
  
  
  METHODS
  Beat-to-beat blood pressure responses to the Valsalva maneuver, interventricular septal 6-[18F]fluorodopamine-derived radioactivity, cardiac extraction fraction of [3H]norepinephrine, appearance rate of norepinephrine in coronary sinus plasma (cardiac norepinephrine spillover) and venous-arterial differences in levels of dihydroxyphenylglycol (DHPG) and endogenous L-dopa.
  
  
  RESULTS
  Of the 29 patients with Parkinson disease, 9 with sympathetic neurocirculatory failure and 11 without had low septal 6-[18F]fluorodopamine-derived radioactivity (2861 +/- 453 Bq/mL per MBq/kg and 5217 +/- 525 Bq/mL per MBq/kg, respectively). All 6 patients with Parkinson disease and decreased 6-[18F]fluorodopamine-derived radioactivity who underwent right-heart catheterization had a decreased cardiac extraction fraction of [3H]norepinephrine and virtually no cardiac norepinephrine spillover or venous-arterial increments in plasma levels of DHPG and L-dopa. Sympathetic neurocirculatory failure and decreased 6-[18F]fluorodopamine-derived radioactivity were unrelated to disease duration, disease severity, or L-dopa treatment
  
  
  CONCLUSIONS
  Many patients with Parkinson disease-including all those with sympathetic neurocirculatory failure-have evidence of cardiac sympathetic denervation. This suggests that loss of catecholamine innervation in Parkinson disease occurs in the nigrostriatal system in the brain and in the sympathetic nervous system in the heart
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1620, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: C
authors.initials: C
authors.lastname: Holmes
authors.forename: S T
authors.initials: ST
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Bruce
authors.forename: L V
authors.initials: LV
authors.lastname: Metman
authors.forename: R O
authors.initials: RO
authors.lastname: Cannon
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D001921:Brain / Q000503:physiopathology; D006328:Cardiac Catheterization; D003937:Diagnosis, Differential; D004298:Dopamine / Q000031:analogs & derivatives*; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D006339:Heart Rate; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014316:Tritium; D014636:Valsalva Maneuver
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014316:Tritium; D007980:Levodopa; D008734:Methoxyhydroxyphenylglycol; C029253:6-fluorodopamine; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine