Abstract 11482: Ivabradine Protects Against Left Ventricular Remodeling in a Mouse Model of Reperfused Myocardial Infarction
Introduction: Ivabradine inhibits the If channel of the sinoatrial node, reducing pacemaker activity and slowing heart rate, and has been shown to reduce death from heart failure and the incidence of myocardial infarction (MI) in selected patients. However, only a very limited number of pre-clinical and preliminary clinical studies have examined the potential of ivabradine to limit LV remodeling after reperfused MI.
Methods: MI was induced in C57Bl/6 mice by 60 min of coronary occlusion followed by reperfusion. After reperfusion, mice were divided into treatment and control groups. The treatment group received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), while the control group received normal water (n=9). Serial short axis cines were acquired at 0.5 mm intervals across the whole LV by echocardiography (Vevo 2100, VisualSonics) at baseline and post-operative days 2, 7, 14 and 28 to assess end-systolic volume (ESV), end-diastolic volume (EDV) and ejection fraction (EF). Heart rates (HR) were measured at 20-25 time points over the course of echocardiography.
Results: Administration of ivabradine reduced HR by 8-16% over the course of 28 days compared to the infarcted controls (p<0.001; Panel A). ESV was significantly reduced in the treated group compared to controls by day 14, an effect that endured to day 28 (p<0.05), although EDV reduction was not statistically significant (Panels B and C). EF was significantly greater in the ivabradine treated group by day 14, an effect that was maintained to day 28 (p<0.01; Panel D). All data is presented as mean ± SEM, where * denotes at p<0.05 and ** denotes p<0.01 vs. infarcted controls.
Conclusions: Ivabradine reduces heart rate in mice to a similar degree as in previously studied animal models. Using high frequency ultrasound, the administration of ivabradine was shown to significantly reduce post-MI systolic heart failure and LV remodeling in a mouse model of reperfused MI.
- © 2011 by American Heart Association, Inc.