OBJECTIVES: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker I(f) current, prevents cardiac dysfunction associated with dyslipidemia. METHODS: New Zealand White rabbits received either a standard diet, a 0.5% cholesterol-enriched diet only (CD), or a 0.5% CD with IVA (17 mg/kg/day) for 12 weeks. HR, left ventricular (LV) systolic function, diastolic function and LV regional myocardial performance index (MPI) were studied using echocardiography. Histological analysis included cardiac interstitial fibrosis and collagen type I fibers. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. RESULTS: IVA reduced HR by approximately 11%. IVA improved MPI and attenuated LV diastolic dysfunction (DD) (92% mild and 8% moderate DD with IVA vs. 54% mild and 46% moderate DD in CD group). IVA also reduced atrial fibrosis (p = 0.027), ventricular fibrosis (p = 0.0002) and ventricular collagen type I (p = 0.0042). IVA decreased plasma angiotensin II levels (p = 0.042), and both angiotensin II and aldosterone levels were correlated with HR (p = 0.038 and 0.008). CONCLUSION: Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.
OBJECTIVES: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker I(f) current, prevents cardiac dysfunction associated with dyslipidemia. METHODS: New Zealand White rabbits received either a standard diet, a 0.5% cholesterol-enriched diet only (CD), or a 0.5% CD with IVA (17 mg/kg/day) for 12 weeks. HR, left ventricular (LV) systolic function, diastolic function and LV regional myocardial performance index (MPI) were studied using echocardiography. Histological analysis included cardiac interstitial fibrosis and collagen type I fibers. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. RESULTS:IVA reduced HR by approximately 11%. IVA improved MPI and attenuated LV diastolic dysfunction (DD) (92% mild and 8% moderate DD with IVA vs. 54% mild and 46% moderate DD in CD group). IVA also reduced atrial fibrosis (p = 0.027), ventricular fibrosis (p = 0.0002) and ventricular collagen type I (p = 0.0042). IVA decreased plasma angiotensin II levels (p = 0.042), and both angiotensin II and aldosterone levels were correlated with HR (p = 0.038 and 0.008). CONCLUSION: Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.
Authors: Yael Yaniv; Syevda Sirenko; Bruce D Ziman; Harold A Spurgeon; Victor A Maltsev; Edward G Lakatta Journal: J Mol Cell Cardiol Date: 2013-05-05 Impact factor: 5.000
Authors: Ulrich Fischer-Rasokat; Jörg Honold; Denise Lochmann; Sebastian Wolter; Christoph Liebetrau; Stephan Fichtlscherer; Helge Möllmann; Ioakim Spyridopoulos; Christian W Hamm Journal: Clin Res Cardiol Date: 2015-12-19 Impact factor: 5.460
Authors: M Schepelmann; P L Yarova; I Lopez-Fernandez; T S Davies; S C Brennan; P J Edwards; A Aggarwal; J Graça; K Rietdorf; V Matchkov; R A Fenton; W Chang; M Krssak; A Stewart; K J Broadley; D T Ward; S A Price; D H Edwards; P J Kemp; D Riccardi Journal: Am J Physiol Cell Physiol Date: 2015-11-04 Impact factor: 4.249