F011 Effect of ivabradine on myocardial systolic function following post-infarction in conscious rabbits

Purpose Heart rate reduction by the selective If current inhibitor ivabradine improves systolic cardiac function in experimental congestive heart failure. Here, we investigated whether its administration would be also beneficial in early post-infarction remodelling following ischemia-reperfusion and particularly at the level of the contractile function of the viable reperfused area. Methods Rabbits were submitted to 20 min of coronary artery occlusion (CAO). Throughout the subsequent 3 weeks of reperfusion, they received continuous infusion of either ivabradine (10 mg/kg/day, n=8) or vehicle (control, n=9) using implanted osmotic pumps. Global and regional systolic functions were assessed by echocardiography and tissue tracking imaging (TTI) (Vingmed System 7), respectively, at baseline (1 week before CAO) and throughout the 3 weeks of reperfusion. TTI was performed in the left ventricular (LV) free wall within the territory subjected to ischemia-reperfusion. Results Throughout the 3 weeks of reperfusion, ivabradine significantly and constantly reduced heart rate (∼-20 %) (Table). Ejection fraction and regional systolic displacement assessed by TTI were significantly improved in ivabradine vs vehicle groups (e.g. +35 % and +36 % at Day 21, respectively). Post-mortem analyses revealed that the area subjected to ischemia was similar in both groups (29±2 and 29±3 % of LV, respectively). This area consisted into a thin infarcted scar (7±1 and 9±2 % of LV, respectively) surrounded by salvaged myocardium and fibrosis. Conclusion Heart rate reduction induced by ivabradine improves global systolic function in the post-infarction period and moreover improves the regional contractility of the remodelled myocardium salvaged by reperfusion. These benefits suggest the potential interest of ivabradine in the management of post-infarcted myocardial dysfunction.