Inhibitory G protein overexpression provides physiologically relevant heart rate control in persistent atrial fibrillation

Alexander Bauer, Amy D. McDonald, Khurram Nasir, Leah Peller, Jeffrey J. Rade, Julie M. Miller, Alan W. Heldman, J. Kevin Donahue

Research output: Contribution to journalArticle

Abstract

Background - The need for new treatment strategies for cardiac arrhythmias has motivated our continuing development of gene therapeutic options. Previously, we reported a decreased heart rate in an acute model of atrial fibrillation after atrioventricular nodal gene transfer. Here, we expand those observations to persistent atrial fibrillation and severe heart failure. Methods and Results - After 3 weeks of atrial fibrillation, domestic swine received atrioventricular nodal gene transfer with adenoviruses encoding β-galactosidase (β-gal), wild-type Gαi2 (wtGi), or constitutively active mutant (cGi). Heart rates in awake, alert animals were not altered by β-gal or wtGi. cGi caused a sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with sedation. A tachycardia-induced cardiomyopathy was present before gene transfer. In the β-gal group, cardiomyopathy worsened over time. In the wtGi group, the condition improved slightly, and in the cGi group, ejection fraction was near normal at the end of the study. TUNEL staining results corroborated this finding. Conclusions - cGi overexpression in the porcine atrioventricular node causes physiologically relevant heart rate control in persistent atrial fibrillation. These data advance the development of gene therapy as a potential treatment for common cardiac arrhythmias.

Original languageEnglish (US)
Pages (from-to)3115-3120
Number of pages6
JournalCirculation
Volume110
Issue number19
DOIs
StatePublished - Nov 9 2004

Keywords

  • Arrhythmia
  • Atrioventricular node
  • Electrophysiology
  • Fibrillation
  • Gene therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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