Key result
In 160 patients, metoprolol (mean 65.2 mg/day) significantly antagonized the atrial fibrillation-induced increase in lateral/polar expression of Cx43 and enhanced transverse conduction velocity.
Why the study?
Does metoprolol improve gap junction remodelling and conduction in left atrial tissue from patients with atrial fibrillation?
Observational (n=160)
Does metoprolol improve gap junction remodelling and conduction in left atrial tissue from patients with atrial fibrillation?
Metoprolol antagonizes AF-induced gap junction remodeling and conduction changes in human atrial tissue, highlighting a potential pharmacological mechanism for its anti-arrhythmic properties.
Metoprolol was associated with attenuated Cx43 remodelling in AF; hypothesis-generating for antiarrhythmic mechanisms in prospective studies.
BACKGROUND AND PURPOSE: We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH: Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day⁻¹) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS: Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS: AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs.
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Dhein et al. (2011) conducted an observational in Atrial fibrillation (n=160). Metoprolol vs. No metoprolol was evaluated on Expression of gap junction proteins Cx43 and Cx40 and conduction velocities. In 160 patients, metoprolol (mean 65.2 mg/day) significantly antagonized the atrial fibrillation-induced increase in lateral/polar expression of Cx43 and enhanced transverse conduction velocity.
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