Connexin gene transfer preserves conduction velocity and prevents atrial fibrillation

Tomonori Igarashi, J. Emanuel Finet, Ayano Takeuchi, Yoshihisa Fujino, Maria Strom, Ian D. Greener, David S. Rosenbaum, J. Kevin Donahue

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

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. Methods and 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.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalCirculation
Volume125
Issue number2
DOIs
Publication statusPublished - 2012 Jan 17
Externally publishedYes

Keywords

  • atrial fibrillation
  • connexin
  • gap junction protein
  • gene therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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