Heart rate is a major determinant of oxygen consumption and metabolic demand. Higher heart rate may induce or exacerbate ischemia and symptoms of angina that is why rate-slowing drugs are considered to be the cornerstone of antianginal therapy. Reperfusion strategies are required to resuscitate the ischemic myocardium. However, reperfusion has the potential to exacerbate lethal tissue injury, a process termed reperfusion injury.Ivabradine is the representative of a novel class of agents that exclusively reduce heart rate through selective inhibition of If current.AIM OF WORK: The aim of the present work is to study the therapeutic effects of ivabradine on cardiac ischemia and reperfusion in in-vivo model of cardiac ischemia/reperfusion in rats and to compare its protective effect to that of propranolol. It also assesses the in-vitro effects of ivabradine on cardiac contractility and heart rate of the isolated rabbit's heart and its effects on vascular reactivity of the isolated rabbit's aorta.METHODS: The study was carried out on 58 male albino rats for in vivo study and 12 rabbits for in vitro study. Rats were subdivided into 3 groups. Prophylaxis groups: (subdivided into 3 subgroup) control prophylactic, The rats were given saline 5 ml /kg orally daily for 15 days before ligation of the left anterior descending (LAD) coronary artery, ivabradine prophylactic, the rats were given ivabradine 5mg /kg orally daily for 15 days before ligation of the (LAD) coronary artery and propranolol prophylactic, the rats were given propranolol 5 mg /kg orally daily for 15 days before ligation of the (LAD) coronary artery. Treated groups: (subdivided into 2 subgroup) control treated, the rats were given saline 1ml/ kg intraperitoneal 5 min after ligation of the LAD and ivabradine treated, the rats were given ivabradine 1mg/ kg intraperitoneal 5 min after ligation of the LAD. Pre-reperfusion groups: (subdivided into 2 subgroup) control pre-reperfusion, the rats were given saline 1ml/ kg intraperitoneal 5 min before reperfusion and ivabradine pre-reperfusion, the rats were given ivabradine 1mg/ kg intraperitoneal 5 min before reperfusion . The heart was exposed to one and half hour ischemia (group 1 and 2) followed by two hours reperfusion (group 3). The changes in the ECG as regard the heart rates and ST segment levels were recorded at the onset of each experiment, 5 minutes, 15 minutes and 1.5 hours after ligation of the LAD in the ischemic groups; in the reperfusion groups, measurements were done at the start of the experiment, 1.5 hours after ligation of LAD artery and 20 minutes after reperfusion. At the end of the experiment heart was removed and stained with Hematoxylin-Eosin stain.For the in vitro study, the effects of gradually increasing doses of ivabradine on the inotropic and chronotropic properties of the isolated perfused mammalian heart were recorded and the effect of cumulative doses of ivabradine on top of the submaximal dose of phenylephrine were measured on the isolated rabbit aortic strips.RESULTS: The control subgroup showed significant increase in heart rate after 1.5 hours of ligation, significant elevation in ST segment level with increasing time of ligation. lvabradine prophylactic showed significant reduction in heart rate, in the level of ST elevation and in size of myocardial infarction similar to that of propranolol. Ivabradine treated and pre-reperfusion also resulted in significant reduction in heart rate, in the level of ST elevation and in size of myocardial infarction. Ivabradine showed relaxant effect on isolated aortic strip of rabbit after cumulative doses. It showed dose dependent reduction in heart rate on isolated rabbit heart with no negative inotropic effect at all doses used.CONCLUSIONS: Induction of ischemia/reperfusion in rats resulted in myocardial injury indicated by occurrence of myocardial infarction, elevation of ST-segment. Both ivabradine and propranolol showed equal protection against ischemic injury as evidenced by reduction in ST segment elevation and in size of myocardial infarction. Ivabradine treatment also showed anti-ischemic property as evidenced by decreasing ST segment elevation and myocardial infarction size. Long term prophylaxis by ivabradine is more effective than ivabradine treatment. The fact that ivabradine is still protective when given before reperfusion points towards mechanisms involved in attenuation of reperfusion injury and post conditioning.