title: Norepinephrine turnover is increased in suprabulbar subcortical brain regions and is related to whole-body sympathetic activity in human heart failure.
abstract: BACKGROUND
  Although it is established that heightened sympathetic drive exists in congestive heart failure (CHF), the reflex processes by which this may occur and the sites in the central nervous system that may be responsible for mediating this process are not yet fully elucidated.
  
  
  RESULTS
  Eight patients with moderate to severe CHF and 8 healthy control subjects underwent simultaneous arterial and bilateral internal jugular venous blood sampling and cerebral venous blood pool scanning for anatomical determination of the origin of internal jugular venous blood flow. We estimated sympathetic nervous activity by measuring total body norepinephrine (NE) spillover using radiotracer methodology and determined brain NE turnover by measuring the internal jugular overflow of NE and its lipophilic metabolites, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Suprabulbar subcortical turnover of NE was significantly greater in CHF patients than in the healthy group (2.77 +/- 0.75 versus 0.66 +/- 0.40 nmol/min, P<0.05). There was a significant positive correlation between suprabulbar subcortical turnover of NE and total body NE spillover (r=0.62, P=0.01).
  
  
  CONCLUSIONS
  This study, for the first time, demonstrates elevated suprabulbar subcortical noradrenergic activity in human CHF and identifies a positive correlation between this and the level of whole-body NE spillover. The findings suggest that the activation of noradrenergic neurons projecting rostrally from the brain stem mediates sympathetic nervous stimulation in CHF.
authors.affiliation: Baker Medical Research Institute, Melbourne, Australia.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hastings
authors.forename: Leonie
authors.initials: L
authors.lastname: Johnston
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001933:Brain Stem / Q000098:blood supply / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D002550:Cerebral Veins / Q000502:physiology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D007601:Jugular Veins / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics; D011669:Pulmonary Wedge Pressure; D017534:Radial Artery / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine