Cardiovascular Research Advance Access [Accepted Manuscript] published online on March 1, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn057
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Effect of metoprolol and ivabradine on left ventricular remodeling and Ca2+ handling in the post-infarction rat heart
M
czewski,, M.D., Ph.D.*,
Address for correspondence: Dr. Micha Mczewski Department of Clinical Physiology Medical Centre of Postgraduate Education Marymoncka 99 01-813 Warszawa, POLAND phone: +48 022 5693 841 fax: +48 022 5693 712 e-mail: maczmich{at}cmkp.edu.pl
AIM: β-Blockers reduce mortality and morbidity in heart failure. Many of their benefits can be explained solely by heart rate reduction. We aimed to verify whether the β-blocker, metoprolol, and the pure heart rate-reducing agent, ivabradine, have the same effects on hemodynamic function, ventricular remodeling and Ca2+ handling in post-myocardial infarction (MI) heart failure in the rat.
METHODS: Metoprolol (250 mg/kg/day) or ivabradine (10 mg/kg/day), offering similar heart rate reduction, or no treatment, was started 24 hours after induction of MI or sham surgery in the rat.
RESULTS: 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, while ivabradine potentiated LV hypertrophy. Metoprolol, but not ivabradine, partially prevented post-MI chronotropic incompetence. Metoprolol markedly, while 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.
CONCLUSIONS: Although both metoprolol and ivabradine comparably prevented post-MI deterioration of hemodynamic 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 heart rate reduction does not account for effects of β-blockade in the post-MI setting.
Time for primary review: 29 days
* both authors equally contributed to the study
Related Article
CiteULike 
Connotea 
Del.icio.us What's this?
Cardiovasc Res 2008 79: 5-6.
This article has been cited by other articles:
|
|
 |
|
  J. Lee, M. A. Stagg, S. Fukushima, G. K. R. Soppa, U. Siedlecka, S. J. Youssef, K. Suzuki, M. H. Yacoub, and C. M. N. Terracciano Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H927 - H936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Heusch, A. Skyschally, P. Gres, P. van Caster, D. Schilawa, and R. Schulz Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction Eur. Heart J., September 2, 2008; 29(18): 2265 - 2275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Goldstein and M. C.P. Haigney Heart-rate reduction and {beta}-blockade in early post-infarction cardiac remodelling Cardiovasc Res, July 1, 2008; 79(1): 5 - 6. [Full Text] [PDF]
|
|