title: Autonomic dysfunction in patients with Brugada syndrome: further biochemical evidence of altered signaling pathways.
abstract: BACKGROUND
  In patients with Brugada syndrome (BrS), life-threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS.
  
  
  RESULTS
  Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5'monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G-proteins (G(i1,2) α), troponin-I (TNI), and phosphorylated TNI were analyzed. Levels of NET, G(i1,2) α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations.
  
  
  CONCLUSIONS
  The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β-adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis.
authors: Department of Cardiology and Angiology Institute of Pharmacology and Toxicology, University Hospital, Münster, Germany.
authors: Matthias
authors: M
authors: Paul
authors: Matthias
authors: M
authors: Meyborg
authors: Peter
authors: P
authors: Boknik
authors: Ulrich
authors: U
authors: Gergs
authors: Wilhelm
authors: W
authors: Schmitz
authors: Günter
authors: G
authors: Breithardt
authors: Thomas
authors: T
authors: Wichter
authors: Joachim
authors: J
authors: Neumann