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Continuous reduction of heart rate by ivabradine cannot prevent deterioration of cardiac function in middle‐aged rats with a large myocardial infarction
Author(s) -
McCooey Daniela,
Bogatyryov Yevgen,
Tomanek Robert J,
Dedkov Eduard I
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.528.5
Subject(s) - ivabradine , medicine , cardiology , myocardial infarction , ejection fraction , cardiac function curve , ventricular remodeling , placebo , heart rate , heart failure , blood pressure , alternative medicine , pathology
A large myocardial infarction (MI) initiates progressive structural remodeling that leads to a decline in left ventricular (LV) performance. Four weeks of heart rate reduction (HRR) in post‐MI rats by ivabradine (IVA), a selective inhibitor of the pacemaker I f current, attenuated LV systolic dysfunction without modifying cardiac remodeling. However, continuation of this beneficial effect after an extended period of IVA treatment remains to be confirmed. Accordingly, we designed our study to determine whether prolonged HRR by IVA alters post‐MI LV remodeling and functional performance. A large MI (>; 50% of the LV free wall) was induced in 12‐month‐old male Sprague‐Dawley rats by ligation of the left coronary artery and the rats were then assigned in two experimental groups. In the first group, rats were treated with IVA i.p. via osmotic pumps in a dose of 10.5 mg/kg/d for 3 months (MI+IVA), while in the second group, rats received placebo (MI). Three months after MI, the infarct size and its composition, LV chamber dimensions and a degree of myocardial hypertrophy were comparable between MI and MI+IVA rats. At the same time, IVA‐treated rats showed a similar reduction in LV ejection fraction compared to untreated MI rats (0.32±0.02 vs. 0.30±0.02, respectively). Our data demonstrate that a prolonged period of HRR by ivabradine cannot prevent deterioration of LV systolic performance in middle‐aged rats after a large MI. Grant Funding Source : Internal Award from the NYCOM Office of Research (E.I. Dedkov) and Research Grant from the IRI Servier (R.J. Tomanek)