Open Access

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
  • View Affiliations

  • 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.

References

1 

Edelmann F, Knosalla C, Mörike K, Muth C, Prien P and Störk S: Chronic heart failure. Dtsch Arztebl Int. 115:124–130. 2018.PubMed/NCBI

2 

Füller M, von Bodman G, Kopf Dr, Brömsen J, Sodian R and Block M: Chronic heart failure with reduced ejection fraction: Standard treatment and new therapeutic options. MMW Fortschr Med. 154:63–70. 2012.(In German).

3 

Lena A, Coats AJS and Anker MS: Metabolic disorders in heart failure and cancer. ESC Heart Fail. 5:1092–1098. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Gyöngyösi M, Winkler J, Ramos I, Do QT, Firat H, McDonald K, González A, Thum T, Díez J, Jaisser F, et al: Myocardial fibrosis: Biomedical research from bench to bedside. Eur J Heart Fail. 19:177–191. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Curtis LH, Whellan DJ, Hammill BG, Hernandez AF, Anstrom KJ, Shea AM and Schulman KA: Incidence and prevalence of heart failure in elderly persons, 1994–2003. Arch Intern Med. 168:418–424. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Hohendanner F, Messroghli D, Bode D, Blaschke F, Parwani A, Boldt LH and Heinzel FR: Atrial remodelling in heart failure: Recent developments and relevance for heart failure with preserved ejection fraction. ESC Heart Fail. 5:211–221. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Richards AM: ST2 and prognosis in chronic heart failure. J Am Coll Cardiol. 72:2321–2323. 2018. View Article : Google Scholar : PubMed/NCBI

8 

Hu DY, Huang DJ, Yuan ZY, Zhao RP, Yan XW and Wang MH; Chinese Investigators of SHIFT Study, : Efficacy and safety analysis of ivabradine hydrochloride treatment of Chinese patients with chronic heart failure: Subgroup analysis of Chinese patients in the SHIFT study. Zhonghua Xin Xue Guan Bing Za Zhi. 45:190–197. 2017.(In Chinese). PubMed/NCBI

9 

Ke Y, Xu D, Li M, Wu Z and Huang Y: Effects of bisoprolol in combination with trimetazidine on the treatment of heart failure and concomitant chronic obstructive pulmonary disease. Pak J Med Sci. 32:1208–1212. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Fragasso G, Palloshi A, Puccetti P, Silipigni C, Rossodivita A, Pala M, Calori G, Alfieri O and Margonato A: A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol. 48:992–998. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Bernardi L, Spadacini G, Bellwon J, Hajric R, Roskamm H and Frey AW: Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure. Lancet. 351:1308–1311. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Suzuki T, Palus S and Springer J: Skeletal muscle wasting in chronic heart failure. ESC Heart Fail. 5:1099–1107. 2018.PubMed/NCBI

14 

Li CC, Chang SR and Shun SC: The self-care coping process in patients with chronic heart failure: A qualitative study. J Clin Nurs. 28:509–519. 2019. View Article : Google Scholar : PubMed/NCBI

15 

López B, Querejeta R, González A, Sánchez E, Larman M and Díez J: Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol. 43:2028–2035. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Wang E-W, Jia X-S, Ruan C-W and Ge Z-R: miR-487b mitigates chronic heart failure through inhibition of the IL-33/ST2 signaling pathway. Oncotarget. 8:51688–51702. 2017.PubMed/NCBI

17 

Boivin-Jahns V and Jahns R: GPCR-autoantibodies in chronic heart failure. Front Biosci. 23:2065–2081. 2018. View Article : Google Scholar

18 

Brennan EJ: Chronic heart failure nursing: Integrated multidisciplinary care. Br J Nurs. 27:681–688. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Vergaro G and Iacoviello M: Is there a ‘renal paradox’ in chronic heart failure? Int J Cardiol. 267:139–140. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Canepa M, Ameri P, Lucci D, Nicolosi GL, Marchioli R, Porcu M, Tognoni G, Franzosi MG, Latini R, Maseri A, et al GISSI-HF Investigators, : Modes of death and prognostic outliers in chronic heart failure. Am Heart J. 208:100–109. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Freitas P, Ferreira AM and Aguiar C: Comparison of prognostic scores in chronic heart failure. JACC Heart Fail. 6:887–888. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Simonavičius J, Knackstedt C and Brunner-La Rocca HP: Loop diuretics in chronic heart failure: How to manage congestion? Heart Fail Rev. 24:17–30. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Wolfson AM, Fong M, Grazette L, Rahman JE and Shavelle DM: Chronic heart failure management and remote haemodynamic monitoring. Heart. 104:1910–1919. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Fudim M, Ganesh A, Green C, Jones WS, Blazing MA, DeVore AD, Felker GM, Kiefer TL, Kong DF, Boortz-Marx RL, et al: Splanchnic nerve block for decompensated chronic heart failure: splanchnic-HF. Eur Heart J. 39:4255–4256. 2018. View Article : Google Scholar : PubMed/NCBI

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September 2019
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Copy and paste a formatted citation
APA
Ma, D., Xu, T., Cai, G., Wu, X., Lei, Z., Liu, X. ... Yang, N. (2019). Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure. Experimental and Therapeutic Medicine, 18, 1639-1644. https://doi.org/10.3892/etm.2019.7730
MLA
Ma, D., Xu, T., Cai, G., Wu, X., Lei, Z., Liu, X., Li, J., Yang, N."Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure". Experimental and Therapeutic Medicine 18.3 (2019): 1639-1644.
Chicago
Ma, D., Xu, T., Cai, G., Wu, X., Lei, Z., Liu, X., Li, J., Yang, N."Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1639-1644. https://doi.org/10.3892/etm.2019.7730