title: Recurrent postural vasovagal syncope: sympathetic nervous system phenotypes.
abstract: BACKGROUND
  The pathophysiology of vasovagal syncope is poorly understood, and the treatment usually ineffective. Our clinical experience is that patients with vasovagal syncope fall into 2 groups, based on their supine systolic blood pressure, which is either normal (>100 mm Hg) or low (70-100 mm Hg). We investigated neural circulatory control in these 2 phenotypes.
  
  
  RESULTS
  Sympathetic nervous testing was at 3 levels: electric, measuring sympathetic nerve firing (microneurography); neurochemical, quantifying norepinephrine spillover to plasma; and cellular, with Western blot analysis of sympathetic nerve proteins. Testing was done during head-up tilt (HUT), simulating the gravitational stress of standing, in 18 healthy control subjects and 36 patients with vasovagal syncope, 15 with the low blood pressure phenotype and 21 with normal blood pressure. Microneurography and norepinephrine spillover increased significantly during HUT in healthy subjects. The microneurography response during HUT was normal in normal blood pressure and accentuated in low blood pressure phenotype (P=0.05). Norepinephrine spillover response was paradoxically subnormal during HUT in both patient groups (P=0.001), who thus exhibited disjunction between nerve firing and neurotransmitter release; this lowered norepinephrine availability, impairing the neural circulatory response. Subnormal norepinephrine spillover in low blood pressure phenotype was linked to low tyrosine hydroxylase (43.7% normal, P=0.001), rate-limiting in norepinephrine synthesis, and in normal blood pressure to increased levels of the norepinephrine transporter (135% normal, P=0.019), augmenting transmitter reuptake.
  
  
  CONCLUSIONS
  Patients with recurrent vasovagal syncope, when phenotyped into 2 clinical groups based on their supine blood pressure, show unique sympathetic nervous system abnormalities. It is predicted that future therapy targeting the specific mechanisms identified in the present report should translate into more effective treatment.
authors.affiliation: Human Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. Gautam.vaddadi@bakeridi.edu.au
authors.forename: Gautam
authors.initials: G
authors.lastname: Vaddadi
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Murray
authors.initials: M
authors.lastname: Esler
authors.forename: Florentia
authors.initials: F
authors.lastname: Socratous
authors.forename: Markus
authors.initials: M
authors.lastname: Schlaich
authors.forename: Reena
authors.initials: R
authors.lastname: Chopra
authors.forename: Nina
authors.initials: N
authors.lastname: Eikelis
authors.forename: Gavin
authors.initials: G
authors.lastname: Lambert
authors.forename: Thomas
authors.initials: T
authors.lastname: Trauer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lambert
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D034284:Dynamin I / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010641:Phenotype; D012008:Recurrence; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D019462:Syncope, Vasovagal / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D034284:Dynamin I; D009638:Norepinephrine