title: Connexin gene transfer preserves conduction velocity and prevents atrial fibrillation.
abstract: BACKGROUND
  Several lines of evidence have suggested that maintenance of atrial fibrillation (AF) depends on reentrant mechanisms. Maintenance of reentry necessitates a sufficiently short refractory period and/or delayed conduction, and AF has been associated with both alterations. Fibrosis, cellular dysfunction, and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF.
  
  
  RESULTS
  Thirty Yorkshire swine were randomized into 2 groups (sinus rhythm and AF), and each group into 3 subgroups: sham-operated control, gene therapy with adenovirus expressing connexin (Cx) 40, and gene therapy with adenovirus expressing Cx43 (n=5 per subgroup). All animals had epicardial gene painting; the AF group had burst atrial pacing. All animals underwent terminal study 7 days after gene transfer. Sinus rhythm animals had strong transgene expression but no atrial conduction changes. In AF animals, controls had reduced and lateralized Cx43 expression, and Cx43 gene transfer restored expression and cellular location to sinus rhythm control levels. In the AF group, both Cx40 and Cx43 gene transfer improved conduction and reduced AF relative to controls.
  
  
  CONCLUSIONS
  Connexin gene therapy preserved atrial conduction and prevented AF.
authors.affiliation: Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Igarashi
authors.forename: J Emanuel
authors.initials: JE
authors.lastname: Finet
authors.forename: Ayano
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Fujino
authors.forename: Maria
authors.initials: M
authors.lastname: Strom
authors.forename: Ian D
authors.initials: ID
authors.lastname: Greener
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenbaum
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Donahue
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control* / Q000628:therapy; D002304:Cardiac Pacing, Artificial; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006329:Heart Conduction System; D013552:Swine; D016896:Treatment Outcome; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein