Activation of IK1 channel by zacopride attenuates left ventricular remodeling in rats with myocardial infarction
Authors: Xiang-Li Cui
Bo-Wei Wu
Li Zhang
Zhi-Qing Zhao
Qi-Long Feng
Qing-Hua Liu
Cheng-Fang Liu
Ji-Min Cao
Tian-E Luo
Xu-Wen Zhai
En-Li Liu
Wei-Fang Zhang
Journal: Journal of Cardiovascular Pharmacology (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: IK1 channels; antiarrhythmic strategy; Zacopride; cardiac remodeling; myocardial infarction
Affiliations: *Department of Physiology, Shanxi Medical University, Taiyuan, China; †Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA; and ‡Department of Physiology, School of Basic Medicine Peking Union Medical College, Beijing, China.

Abstract:  Activating IK1 channels is considered to be a promising antiarrhythmic strategy. Zacopride has been identified as a selective IK1 channel agonist and can suppress triggered arrhythmias. Whether this drug also exerts a beneficial effect on cardiac remodeling is unknown, and the present study sought to address this question. Cardiac remodeling was induced through coronary ligation-induced myocardial infarction (MI) in male Sprague-Dawley rats. Zacopride (15 µg/kg) was administered (intraperitoneally) daily for 28 days after MI to determine whether it could attenuate MI-induced cardiac remodeling. A 4-week treatment with zacopride attenuated post-MI cardiac remodeling, as shown by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension and the increased ejection fraction and fractional shortening in zacopride-treated animals compared with animals treated with vehicle (all P &lt; 0.05). Furthermore, zacopride significantly decreased myocardial collagen deposition, cardiomyocyte hypertrophy, the plasma level of brain natriuretic peptide, and cardiomyocyte ultrastructural injury. Zacopride also upregulated the expression of the IK1 channel protein and downregulated the expression of phosphorylated p70S6 kinase (p-p70S6K) and mTOR. These beneficial effects of zacopride were partially abolished by the IK1 channel blocker chloroquine. We conclude that the activation of IK1 channel by zacopride attenuates post-MI cardiac remodeling by suppressing mTOR-p70S6 kinase signaling. 

Retracted: Yes

PubPeer comments:
 March 2015 retraction notice, which states: *We request to retract our article published in the October 2014 issue of the Journal of Cardiovascular Pharmacology, entitled u201cActivation of IK1 Channel by Zacopride Attenuates Left Ventricular Remodeling in Rats with Myocardial Infarction,u201d1 because of the flawed data presentations. We deeply apologize for making such serious and obvious mistakes in this article, which has the potential to mislead individuals working in the field. I (B-W.W.) discussed with all the coauthors of this article, and we all agree to retract this article. I write this letter to you on behalf of all coauthors, including Dr Ji-Min Cao and Dr Zhi-Qing Zhao.* , 
 The retraction notice does not give a lot of detail, so here is a post-mortem analysis. Figure 1A: * Red boxes: The MI+Chlor and Mi_Zac_Chlor panels appear to show an overlap, albeit at a different zoom factor. ![file] , 
 Figure 2. * Yellow and blue boxes: Panels A (Sham), B (Sham + Zac), and D (MI + Zac) appear to show areas of overlap. ![file] ,