What is the clinical evidence from this study?

Study design: Case-Control. Population: Brugada syndrome (n=13). Intervention: Brugada syndrome vs. Controls. Primary outcome: Concentrations of key components of the sympathoadrenergic signaling pathways (NE, Epi, NET, cAMP, Gi1,2 α, TNI, and phosphorylated TNI).

May 23, 2011

Autonomic Dysfunction in Patients with Brugada Syndrome: Further Biochemical Evidence of Altered Signaling Pathways

Key Result

Patients with Brugada syndrome had reduced cyclic AMP and norepinephrine concentrations in endomyocardial biopsies compared to controls.

Study Design

Type

Case-Control (n=13)

Structured PICO

Does the biochemical profile of sympathoadrenergic signaling pathways differ in endomyocardial biopsies of patients with Brugada syndrome compared to controls?

Population

13 individuals, including 8 patients with Brugada syndrome and 5 controls, who underwent endomyocardial biopsy to analyze sympathoadrenergic signaling pathways.

Exposure

Analysis of endomyocardial biopsies for key components of sympathoadrenergic signaling pathways

Comparator

Controls without Brugada syndrome

Outcome

Concentrations of norepinephrine (NE), epinephrine (Epi), NE transport (NET) carrier protein, cAMP, inhibitory G-proteins (G(i1,2) α), troponin-I (TNI), and phosphorylated TNIsurrogate

Patients with Brugada syndrome exhibit reduced myocardial norepinephrine and cAMP concentrations, providing biochemical evidence of adrenergic dysfunction that may contribute to arrhythmogenesis.

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. 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.

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Cite This Study

Paul et al. (Mon,) conducted a case-control in Brugada syndrome (n=13). Brugada syndrome vs. Controls was evaluated on Concentrations of key components of the sympathoadrenergic signaling pathways (NE, Epi, NET, cAMP, Gi1,2 α, TNI, and phosphorylated TNI). Patients with Brugada syndrome had reduced cyclic AMP and norepinephrine concentrations in endomyocardial biopsies compared to controls.

synapsesocial.com/papers/6a22c902a1bd7ea8dd11db3e https://doi.org/https://doi.org/10.1111/j.1540-8159.2011.03127.x

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