We tested the hypothesis that heart rate (HR) reduction, induced by the 
selective hyperpolarization-activated current inhibitor ivabradine (Iva), might 
improve left ventricular (LV) function, structure, and electrical remodeling in 
severe post-myocardial infarction (MI) chronic heart failure (HF). MI was 
produced in adult male Wistar rats. After 2 mo, echocardiography was performed 
before the randomization into MI and MI + Iva (10 mg x kg(-1) x day(-1)) groups. 
After 3 mo of treatment, echocardiography and 24-h telemetry were recorded. 
Cardiac collagen, mRNA, and protein expressions of angiotensin-converting enzyme 
(ACE) and ANG II type 1 (AT(1)) receptor were quantified. As a result, at 2 mo 
post-MI, all rats displayed severe congestive HF signs (ejection fraction < 
30%). At 5 mo post-MI, body and heart weights were similar in the MI and MI + 
Iva groups. LV ejection fraction and LV end-diastolic pressure were worsened in 
the MI group, whereas both were improved with Iva. Iva reduced HR by 10.4% (P < 
0.03 vs. MI) and ventricular premature complexes by 89% (P < 0.03) and improved 
HR variability (standard deviation of the RR interval) by 22% (P < 0.05). There 
were no effects of Iva on PR, QRS, and QT durations. Interstitial fibrosis in 
the MI-remote LV was markedly reduced by Iva (4.0 +/- 0.1 vs. 1.8 +/- 0.1%, P < 
0.005). Increases in ventricular gene and protein expressions of ACE and AT(1) 
receptor in MI were completely blunted by Iva. In conclusion, these data 
indicated that HR reduction by Iva prevents the worsening of LV dysfunction and 
remodeling that may be related to a downregulation of cardiac 
renin-angiotensin-aldosterone system transcripts. Such beneficial effects of Iva 
on cardiac remodeling open new clinical perspectives for the treatment of severe 
HF.