title: Effect and mechanism of fluoxetine on electrophysiology in vivo in a rat model of postmyocardial infarction depression.
abstract: BACKGROUND
  Major depression is diagnosed in 18% of patients following myocardial infarction (MI), and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism.
  
  
  RESULTS
  Eighty adult male Sprague Dawley rats (200-250 g) were randomly assigned to five groups: normal control (control group), MI (MI group), depression (depression group), post-MI depression (model group), and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group). MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS). Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P<0.05 vs model group). Fluoxetine significantly increased the ventricular fibrillation threshold compared with the model group (20.20±9.32 V vs 14.67±1.85 V, P<0.05). Expression of Kv4.2 was significantly reduced by 29%±12%, 24%±6%, and 41%±15%, respectively, in the MI group, CMS group, and model group, which could be improved by fluoxetine (30%±9%). But fluoxetine showed no improvement on the MI-induced loss of Cx43.
  
  
  CONCLUSIONS
  The susceptibility to ventricular arrhythmias was increased in depression and post-MI depression rats, and fluoxetine may reduce the incidence of ventricular arrhythmia in post-MI depression rats and thus improve the prognosis. This may be related in part to the upregulation of Kv4.2 by fluoxetine.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China ; Masonic Medical Research Laboratory, Utica, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China ; Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D054849:Cardiac Electrophysiology; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005473:Fluoxetine
keywords: arrhythmias; depression; electrophysiology; myocardial infarction; pharmacology