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Cardiovasc Res. 2008 Jul 1;79(1):42-51. doi: 10.1093/cvr/cvn057. Epub 2008 Mar 1.

Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart.

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  • 1Department of Clinical Physiology, Medical Centre of Postgraduate Education, Marymoncka 99, 01-813 Warszawa, Poland. maczmich@cmkp.edu.pl

Abstract

AIMS:

beta-Blockers reduce mortality and morbidity in heart failure. Many of their benefits can be explained solely by heart rate reduction (HRR). We aimed to verify whether the beta-blocker, metoprolol, and the pure heart-rate-reducing agent, ivabradine, have the same effects on haemodynamic function, ventricular remodeling, and Ca2+ handling in post-myocardial infarction (MI) heart failure in rat.

METHODS AND RESULTS:

Metoprolol (250 mg/kg/day) or ivabradine (10 mg/kg/day), offering similar HRR, or no treatment, was started 24 h after an induction of MI or sham surgery in rat. Eight weeks post-MI metoprolol and ivabradine similarly partially prevented deterioration of left ventricular (LV) ejection fraction and reduced post-MI LV wall stress. However, metoprolol partially prevented LV dilation, whereas ivabradine potentiated LV hypertrophy. Metoprolol, but not ivabradine, partially prevented post-MI chronotropic incompetence. Metoprolol markedly, whereas ivabradine mildly, increased the amplitude of the Ca2+ transient in post-MI cardiomyocytes. Ivabradine, but not metoprolol, partially prevented the MI-induced depression of sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity, while metoprolol, but not ivabradine, suppressed Na+/Ca2+ exchanger (NCX) overactivity and normalized Ca2+ sensitivity of ryanodine receptors.

CONCLUSION:

Although both metoprolol and ivabradine comparably prevented post-MI deterioration of haemodynamic function in the rat, metoprolol had additional potentially beneficial effects; it prevented LV dilation and hypertrophy, chronotropic incompetence, strongly increased contractility of isolated cardiomyocytes, and prevented the potentially proarrhythmic increase in NCX activity. This indicates that pure HRR does not account for effects of beta-blockade in the post-MI setting. Metoprolol and ivabradine similarly improve LV function, although differently affect LV morphology and cellular Ca2+ handling in the post-infarction rat heart.

PMID:
18310678
[PubMed - indexed for MEDLINE]
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