SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic

Cardiovasc Res. 2012 Jun 1;94(3):450-9. doi: 10.1093/cvr/cvs107. Epub 2012 Feb 27.


Aims: Reentry accounts for most life-threatening arrhythmias, complicating myocardial infarction, and therapies that consistently prevent reentry from occurring are lacking. In this study, we compare antiarrhythmic effects of gene transfer of green fluorescent protein (GFP; sham), the skeletal muscle sodium channel (SkM1), the liver-specific connexin (Cx32), and SkM1/Cx32 in the subacute canine infarct.

Methods and results: Immediately after ligation of the left anterior descending artery, viral constructs were implanted in the epicardial border zone (EBZ). Five to 7 days later, efficient restoration of impulse propagation (narrow QRS and local electrogram duration) occurred in SkM1, Cx32, and SkM1/Cx32 groups (P< 0.05 vs. GFP). Programmed electrical stimulation from the EBZ induced sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) in 15/22 GFP dogs vs. 2/12 SkM1, 6/14 Cx32, and 8/10 SkM1/Cx32 (P< 0.05 SkM1 vs. GFP). GFP, SkM1, and SkM1/Cx32 had predominantly polymorphic VT/VF, whereas in Cx32 dogs, monomorphic VT predominated (P< 0.05 for Cx32 vs. GFP). Tetrazolium red staining showed significantly larger infarcts in Cx32- vs. GFP-treated animals (P< 0.05).

Conclusion: Whereas SkM1 gene transfer reduces the incidence of inducible VT/VF, Cx32 therapy to improve gap junctional conductance results in larger infarct size, a different VT morphology, and no antiarrhythmic efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / therapeutic use
  • Arrhythmias, Cardiac / drug therapy*
  • Connexins / genetics
  • Connexins / metabolism*
  • Dogs
  • Electric Stimulation
  • Electrocardiography
  • Gap Junctions / drug effects*
  • Male
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology*
  • Rats
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Ventricular Fibrillation / drug therapy*
  • Ventricular Fibrillation / physiopathology


  • Anti-Arrhythmia Agents
  • Connexins
  • Muscle Proteins
  • Scn4a protein, rat
  • Sodium Channels
  • connexin 32