title: SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology,  Columbia University, 630 West 168 Street, PH 7W-321, New York, NY 10032,  USA.
authors.forename: Gerard J J
authors.initials: GJ
authors.lastname: Boink
authors.forename: David H
authors.initials: DH
authors.lastname: Lau
authors.forename: Iryna N
authors.initials: IN
authors.lastname: Shlapakova
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: Helen E
authors.initials: HE
authors.lastname: Driessen
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Tove S
authors.initials: TS
authors.lastname: Rosen
authors.forename: Nazira
authors.initials: N
authors.lastname: Őzgen
authors.forename: Heather S
authors.initials: HS
authors.lastname: Duffy
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kryukova
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Richard B
authors.initials: RB
authors.lastname: Robinson
authors.forename: Peter R
authors.initials: PR
authors.lastname: Brink
authors.forename: Ira S
authors.initials: IS
authors.lastname: Cohen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D017629:Gap Junctions / Q000187:drug effects*; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D000097002:Gap Junction beta-1 Protein
chemical_list: D000889:Anti-Arrhythmia Agents; D017630:Connexins; D009124:Muscle Proteins; D015222:Sodium Channels; D000097002:Gap Junction beta-1 Protein; C466180:Scn4a protein, rat