Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure

Ma,Dongwen; Xu,Tong; Cai,Guoqiang; Wu,Xilin; Lei,Zhendong; Liu,Xinmei; Li,Junying; Yang,Ning

doi:10.3892/etm.2019.7730

Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure

Authors:
- Dongwen Ma
- Tong Xu
- Guoqiang Cai
- Xilin Wu
- Zhendong Lei
- Xinmei Liu
- Junying Li
- Ning Yang
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Affiliations: Department of Cardiac Critical Care Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Cardiology, The First Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, Guangxi 545002, P.R. China, Department of Interventional Cardiology, General Hospital of Guizhou Panjiang Investment Holding Group Co., Ltd., Liupanshui, Guizhou 553536, P.R. China, Health Management Center, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
Published online on: July 3, 2019 https://doi.org/10.3892/etm.2019.7730
Pages: 1639-1644
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Effects of ivabradine hydrochloride (Iva) and trimetazidine on myocardial fibrosis (MF) in rats with chronic heart failure (CHF) werφe explored. Fifty Wistar rats were randomly divided into sham operation, model, Iva, trimetazidine and combined drug group with 10 rats each. All rats except those in sham operation group were subjected to establish CHF model by constricting the abdominal aorta. After successful modeling, rats in the sham operation and model group received normal saline (10 mg/kg) gavage daily, the Iva group received Iva (10 mg/kg) gavage, the trimetazidine group received trimetazidine (10 mg/kg) gavage, and the combined drug group were given Iva (10 mg/kg) and trimetazidine (10 mg/kg) gavage for 12 weeks. The changes of hemodynamic indexes and heart rate, connective tissue growth factor (CTGF) and superoxide dismutase (SOD) levels as well as transforming growth factor β1 (TGF-β1) and collagen I (COL-I) expression levels in myocardial tissue of each group were detected. Compared with sham operation group, the left ventricular end-diastolic pressure (LVEDP) level, CTGF expression, TGF-β1 mRNA and COL-I mRNA expression levels in model group increased significantly, but the ± dp/dtmax and SOD content in myocardial tissue decreased significantly. Compared with model group, the LVEDP level, CTGF expression, TGF-β1 mRNA and COL-I mRNA expression levels in Iva group, trimetazidine group and combined drugs decreased significantly, but the ± dp/dtmax and the SOD content in myocardial tissue increased significantly (P<0.05). Changes in the combined drug group were the most notable (P<0.05). Iva combined with trimetazidine reduces LVEDP in rat with CHF, increases SOD content, and inhibits CTGF expression and TGF-β1 and COL-I expression levels in myocardial tissues, thus achieving the inhibitory effect on MF.

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