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Molecules 2012, 17(5), 4924-4935; doi:10.3390/molecules17054924

The Biological Effects of Ivabradine in Cardiovascular Disease

1
Department of Medicine and Science of Aging, University G. d’Annunzio, 66123 Chieti, Italy
2
Cardiology Unit San Camillo De Lellis Hospital, Manfredonia, Foggia 71121, Italy
*
Author to whom correspondence should be addressed.
Received: 17 January 2012 / Revised: 27 March 2012 / Accepted: 16 April 2012 / Published: 30 April 2012
(This article belongs to the Special Issue Ivabradine)
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Abstract

A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD) have demonstrated that heart rate (HR) is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces cardiac work, thereby diminishing myocardial oxygen demand. Several experimental studies in animals, including dogs and pigs, have clarified the beneficial effects of ivabradine associated with HR lowering. Ivabradine is a selective inhibitor of the hyperpolarisation activated cyclic-nucleotide-gated funny current (If) involved in pacemaker generation and responsiveness of the sino-atrial node (SAN), which result in HR reduction with no other apparent direct cardiovascular effects. Several studies show that ivabradine substantially and significantly reduces major risks associated with heart failure when added to guideline-based and evidence-based treatment. However the biological effect of ivabradine have yet to be studied. This effects can appear directly on myocardium or on a systemic level improving endothelial function and modulating immune cell migration. Indeed ivabradine is an ‘open-channel’ blocker of human hyperpolarization-activated cyclic nucleotide gated channels of type-4 (hHCN4), and a ‘closed-channel’ blocker of mouse HCN1 channels in a dose-dependent manner. At endothelial level ivabradine decreased monocyte chemotactin protein-1 mRNA expression and exerted a potent anti-oxidative effect through reduction of vascular NADPH oxidase activity. Finally, on an immune level, ivabradine inhibits the chemokine-induced migration of CD4-positive lymphocytes. In this review, we discuss the biological effects of ivabradine and highlight its effects on CAD.
Keywords: heart rate; ivabradine; funny current heart rate; ivabradine; funny current
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Speranza, L.; Franceschelli, S.; Riccioni, G. The Biological Effects of Ivabradine in Cardiovascular Disease. Molecules 2012, 17, 4924-4935.

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