title: Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Clinic for Cardiac Surgery, University of Leipzig, Leipzig, Germany. dhes@medizin.uni-leipzig.de
authors.forename: S
authors.initials: S
authors.lastname: Dhein
authors.forename: S
authors.initials: S
authors.lastname: Rothe
authors.forename: A
authors.initials: A
authors.lastname: Busch
authors.forename: D M
authors.initials: DM
authors.lastname: Rojas Gomez
authors.forename: A
authors.initials: A
authors.lastname: Boldt
authors.forename: A
authors.initials: A
authors.lastname: Reutemann
authors.forename: T
authors.initials: T
authors.lastname: Seidel
authors.forename: A
authors.initials: A
authors.lastname: Salameh
authors.forename: B
authors.initials: B
authors.lastname: Pfannmüller
authors.forename: A
authors.initials: A
authors.lastname: Rastan
authors.forename: M
authors.initials: M
authors.lastname: Kostelka
authors.forename: F W
authors.initials: FW
authors.lastname: Mohr
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D000097003:Gap Junction alpha-5 Protein
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D018031:Connexin 43; D017630:Connexins; D008790:Metoprolol; D000097003:Gap Junction alpha-5 Protein