Effect and mechanism of fluoxetine on electrophysiology in vivo in a rat model of postmyocardial infarction depression
Authors Liang JJ, Yuan X, Shi S, wang F, chen Y, qu C, chen J, Hu D, Yang B
Received 15 October 2014
Accepted for publication 20 November 2014
Published 10 February 2015 Volume 2015:9 Pages 763—772
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Shu-Feng Zhou
Jinjun Liang,1,2 Xiaoran Yuan,1,2 Shaobo Shi,1,2 Fang Wang,1,2 Yingying Chen,1,2 Chuan Qu,1,2 Jingjing Chen,1,2 Dan Hu,1–3 Yang Bo1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China; 3Masonic Medical Research Laboratory, Utica, NY, USA
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.
Methods and 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.
Conclusion: 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.
Keywords: depression, myocardial infarction, electrophysiology, arrhythmias, pharmacology
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