November 23, 2020Archives of Medical ScienceOpen Access

Effects of ivabradine on ventricular electrophysiological remodeling after myocardial infarction in rats

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Why the study?

The study was designed to investigate the effects of ivabradine on ventricular electrophysiological remodeling after myocardial infarction in rats.

Does ivabradine alone or in combination with metoprolol improve ventricular electrophysiological remodeling and reduce ventricular arrhythmias after myocardial infarction in rats?

Structured PICO

Does ivabradine alone or in combination with metoprolol improve ventricular electrophysiological remodeling and reduce ventricular arrhythmias after myocardial infarction in rats?

Population

60 male Sprague-Dawley rats, weighing 230-280 g, with myocardial infarction induced by left anterior descending (LAD) coronary artery ligation.

Intervention

Ivabradine 10 mg/(kg × day) by gavage, Metoprolol 50 mg/(kg × day) by gavage, or a combination of both (Ivabradine 10 mg/(kg × day) + Metoprolol 50 mg/(kg × day)), started 24 hours after LAD ligation and continued for 4 weeks.

Comparator

MI group (LAD ligation + normal diet without drug intervention) and sham group (ligature without ligation + normal diet).

Outcome

Ventricular electrophysiological parameters (induction rate and fatality rate of VT/VF, QT, QTc, VERP, VERPd), morphological characteristics (infarction area, collagen volume fraction), and p-Cx43 expression at 4 weeks.surrogate

Ivabradine combined with metoprolol synergistically reduces ventricular arrhythmias and improves structural and electrical remodeling post-myocardial infarction in a rat model.

Limitations

Only male rats were used in this study in order to control for the effects of gender.

Implication

Rat MI model data suggest IVA may alter post-MI electrophysiology; leaves open human translation and clinical relevance.

Abstract

Introduction This study aims to investigate the effects of ivabradine (IVA) on ventricular electrophysiological remodeling after myocardial infarction (MI) in rats. Material and methods A total of 60 male Sprague-Dawley rats were randomly divided into five groups: an MI group, an IVA group, a metoprolol (MET) group, an IVA + MET group, and a sham group. After a four-week intervention, the ventricular electrophysiological parameters were detected by multichannel electrophysiological polygraph. Then, the morphological characteristics were evaluated using hematoxylin and eosin (H&E) and Masson’s staining, and the expression of phosphorylated connexin 43 (p-Cx43) in the left ventricular wall was detected through immunohistochemistry and the Western blot test. Results The electrophysiological examination revealed that the induction rate and fatality rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) were lower in both the IVA and the MET group, compared with the MI group (6/12, 6/12 vs. 10/11; and 1/12, 1/12 vs. 5/11; all p < 0.05), as well as the IVA + MET group (1/11 vs. 10/11, p < 0.01; and 1/11 vs. 5/11, p < 0.05). The induction rate of VT/VF was lower in the IVA + MET group, compared to the MET group (1/11 vs. 6/12, p < 0.05). H&E and Masson’s staining revealed that compared with the MI group, the left ventricular infarction area was lower in the IVA, MET, and IVA + MET groups (p < 0.05, p < 0.05, and p < 0.01, respectively), while collagen volume fraction (CVF) also was lower in the other groups (all p < 0.01). The left ventricular infarction area and CVF both were lower in the IVA + MET group, compared to the MET group (p < 0.05 and p < 0.01, respectively). The immunohistochemistry and Western blot revealed that p-Cx43 expression was higher in the treatment groups, compared with the MI group (all p < 0.01). Conclusions IVA can reduce the incidence of ventricular arrhythmia after MI in male rats by improving both structural and electrical remodeling, and the combination of IVA and MET is even more effective.