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Autonomic Dysfunction in Patients with Brugada Syndrome: Further Biochemical Evidence of Altered Signaling Pathways.
MedLine Citation:
PMID:  21605134     Owner:  NLM     Status:  Publisher    
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. Methods and 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. (PACE 2011; 1-7).
Matthias Paul; Matthias Meyborg; Peter Boknik; Ulrich Gergs; Wilhelm Schmitz; Günter Breithardt; Thomas Wichter; Joachim Neumann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-23
Journal Detail:
Title:  Pacing and clinical electrophysiology : PACE     Volume:  -     ISSN:  1540-8159     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7803944     Medline TA:  Pacing Clin Electrophysiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.
Department of Cardiology and Angiology Institute of Pharmacology and Toxicology, University Hospital, Münster, Germany Institute of Pharmacology and Toxicology, Martin-Luther-University Halle-Wittenberg, Halle, Germany Department of Cardiology, Niels-Stensen-Kliniken, Marienhospital Osnabrück, Osnabrück, Germany.
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