Chonnam Med J.  2018 Sep;54(3):167-172. 10.4068/cmj.2018.54.3.167.

Effects of Ivabradine on Left Ventricular Systolic Function and Cardiac Fibrosis in Rat Myocardial Ischemia-Reperfusion Model

• Kim HB
• Hong YJ
• Park HJ
• Ahn Y
• Jeong MH

• KMID: 2420884
• DOI: http://doi.org/10.4068/cmj.2018.54.3.167

Abstract

We evaluated the effects of Ivabradine on left ventricle (LV) ejection fraction (EF) and LV infarcted tissue in the rat myocardial ischemia-reperfusion model. Twenty rats were randomly assigned to group 1 (ischemia-reperfusion, no treatment, n=10) and group 2 (ischemia-reperfusion + Ivabradine 10 mg/kg, n=10). Ivabradine was administered for 28 days. Echocardiography was performed at 7 days and at 28 days after the induction of ischemia-reperfusion injury. Cardiac fibrosis induced by ischemia-reperfusion injury was evaluated by Masson's trichrome staining. The infarct size was quantified using the Image J program. At the 28-day follow-up, LVEF was significantly higher (36.02±6.16% vs. 45.72±2.62%, p<0.001) and fractional shortening was significantly higher (15.23±2.84% vs. 20.13±1.38%, p<0.001) in group 2 than group 1. Delta (28 day minus 7 day) EF was significantly higher in group 2 than group 1 (−4.36±3.49% vs. 4.31±5.63%, p<0.001). Also, heart rate (beats/min) was significantly lower in group 2 than group 1 (251.67±25.19 vs. 199.29±31.33, p=0.025). Group 2 had a smaller infarct size (40.70±8.94% vs. 30.19±5.89%, p<0.01) than group 1 at 28-day follow-up. Oral administration of Ivabradine could improve LV systolic function and reduce infarcted tissue area in rat myocardial ischemia-reperfusion model.

Keyword

Myocardial Ischemia; Myocardial Reperfusion Injury; Echocardiography; Ivabradine

MeSH Terms

Administration, Oral
Animals
Echocardiography
Fibrosis*
Follow-Up Studies
Heart Rate
Heart Ventricles
Myocardial Ischemia
Myocardial Reperfusion Injury
Rats*
Reperfusion Injury

Figure

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  FIG. 1 Ischemia-reperfusion injury protocol.

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  FIG. 2 Changes in cardiac parameters by echocardiography. (A) Left ventricle internal diameter at diastole (LVIDd), (B) left ventricle internal diameter at systole (LVIDs), (C) ejection fraction (EF), (D) % fractional shortening (FS), (E) delta ejection fraction, and (F) heart rate. IR: ischemia-reperfusion. ***p<0.001, *p=0.025.

• 

  FIG. 3 (A) Masson's trichrome stain, and (B) measurement of infract size. IR: ischemia-reperfusion. **p<0.01.

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