title: [Effects of combined amiodarone and antiarrhythmic peptide use on the cardiac gap junctions and incidence of induced ventricular arrhythmias in healed myocardial infarction rabbit models].
abstract: OBJECTIVE
  The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.
  
  
  METHODS
  Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.
  
  
  RESULTS
  The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.
  
  
  CONCLUSIONS
  The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lian-Dong
authors.initials: LD
authors.lastname: Li
authors.forename: Cun-Tai
authors.initials: CT
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Ruan
authors.forename: Ming-Ke
authors.initials: MK
authors.lastname: Ni
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Wang
authors.forename: Xing-Fen
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000638:Amiodarone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D018031:Connexin 43 / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D009842:Oligopeptides; C029579:antiarrhythmic peptide; D000638:Amiodarone