the biological effects of ivabradine in cardiovascular diseaseivabradine在心血管疾病的生物效应.pdf

Molecules 2012, 17, 4924-4935; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review The Biological Effects of Ivabradine in Cardiovascular Disease Lorenza Speranza 1,*, Sara Franceschelli 1 and Graziano Riccioni 2 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; E-Mail: l.speranza@unich.it; Tel.:+39-871-355-4550; Fax: +39-871-355-4551. Received: 17 January 2012; in revised form: 27 March 2012 / Accepted: 16 April 2012 / Published: 30 April 2012 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. Seve