Long-Term Heart Rate Reduction Induced by the Selective I _f Current Inhibitor Ivabradine Improves Left Ventricular Function and Intrinsic Myocardial Structure in Congestive Heart Failure

Abstract

Background-Heart rate reduction (HRR) improves left ventricular (LV) filling, increases myocardial O 2 supply, and reduces myocardial O 2 consumption, which are all beneficial in congestive heart failure (CHF). However, the long-term effects of HRR on cardiac function and remodeling are unknown. Methods and Results-We assessed, in rats with CHF, the effects of long-term HRR induced by the selective I f current inhibitor ivabradine (as food admix for 90 days starting 7 days after coronary artery ligation). To assess intrinsic modifications of LV tissue induced by long-term HRR, all parameters were reassessed 3 days after interruption of treatment. Ivabradine decreased heart rate over the 90-day treatment period (Ϫ18% versus untreated at 10 mg · kg Ϫ1 · d

Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy?

“…We found that effective HR reduction (a mean of 25.9 beats/min) was hemodynamically safe and tolerated as it was not associated with symptoms or signifi cant change in both systolic and diastolic blood pressure. These fi ndings are supported by the results of Mulder et al (7) who found that blood pressure was little affected by the drug, with no hypotension at peak or through drug effect with any dose of ivabradine.…”

“…In the reported clinical trials there were few problems with drug-induced bradycardia and minimal patient withdrawal (7).…”

Effects of ivabradine therapy on heart failure biomarkers

“…Results in experimental studies are consistent with the effects of ivabradine on cardiac remodeling [11]. In a rat model of chronic mild HF, ivabradine preserved cardiac output and improved LV function and geometry [17]. These changes were linked to modifications in the extracellular matrix and in cardiac myocyte function.…”

Ivabradine therapy and correction of the target organ pathology in patients with ischemic chronic heart failure

“…При этом было отме-чено, что подобное действие ивабрадина связано, скорее всего, с регуляцией РААС, поскольку было найдено, что ивабрадин уменьшает количество кол-лагена в миокарде, экспрессию АПФ и ангиотензи-новых рецепторов 1 типа к ангиотензину II [23]. В данной работе также было определено, что ивабра-дин изменяет коллагенообразование в миокарде у крыс с постинфарктной сердечной недостаточно-стью за счет увеличения плотности капилляров [24]. P. Becher et al в эксперименте установили, что у крыс с ангиотензин II -индуцированной сердечной недо-статочностью ивабрадин, в отличие от метопролола, достоверно улучшал систолическую и диастоличе-скую функцию левого желудочка за счет регресса гипертрофии, фиброза, воспаления и апоптоза мио-карда, возможно и гладкомышечных клеток сосудов [25].…”