Cardioprotective effects of the Ιf current inhibition by ivabradine during cardiac dysfunction.

Heart rate is a fundamental determinant of cardiac function. Normally, the increase in heart rate is accompanied by increased cardiac function. But under pathological conditions such as myocardial infarction and heart failure, accelerated heart rate may become detrimental as it decreases the diastolic time for left ventricular filling and myocardial perfusion but increases left ventricular myocardial oxygen demand. Therefore, heart rate reduction is an appropriate strategy to protect cardiac function. Heart rate reduction can be achieved by different bradycardic drugs, including beta-blockers, calcium channel blockers and selective f-channel inhibitors. By competing with norepinephrine and epinephrine for binding sites, beta-blockers block beta-adrenoceptor-mediated responses to sympathetic stimulation. This induces heart rate reduction and negative inotropy. Calcium channel blockers block calcium influx via specific calcium channels, causing vasodilation and decreases in heart rate, conduction velocity within the heart and myocardial force generation. The selective f-channel inhibitor, ivabradine, inhibits If currents that play an exclusive role in pacemaking and thereby slows heart rate without altering myocardial inotropy. Since these drugs differ in their mechanisms of action, they may cause different beneficial and side effects and thus different outcome according to pathological states. After briefly describing the mechanisms involved in beta-blockers and calcium channel blockers, this review focuses on the bradycardic property of ivabradine and its pleiotropic actions.