Increased heart rate and atherosclerosis: Potential implications of ivabradine therapy

Blanco-Palacios, Gabriela; Abreu-González, Pedro

doi:10.4330/wjc.v3.i4.101

Cited by 24 publications

(15 citation statements)

References 34 publications

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“…This reduction may go beyond heart rate reduction (HRR) as demonstrated by Custodis et al23 in their animal model: ivabradine administration reduced oxidative stress by reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, superoxide production, and lipid peroxidation, although the mechanisms are still not well understood. These data were confirmed in several human studies 18,24–34…”

Section: Additional Beneficial Pharmacological Propertiessupporting

confidence: 76%

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Scicchitano¹,

Cortese²,

Ricci³

et al. 2014

DDDT

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Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

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Section: Additional Beneficial Pharmacological Propertiessupporting

confidence: 76%

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Scicchitano¹,

Cortese²,

Ricci³

et al. 2014

DDDT

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“…Our results also showed that metoprolol treatment significantly slowed the heart rate and other hemodynamic parameters, which could also reduce inflammation [37,38]. Thus, metoprolol may suppress sympathetic nerve sprouting indirectly through its antiinflammatory effects [6,7,8].…”

Section: Discussionmentioning

confidence: 57%

Metoprolol-Mediated Amelioration of Sympathetic Nerve Sprouting after Myocardial Infarction

Wang

Liu²,

Suo³

et al. 2013

Cardiology

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Objectives: Systemic or local inflammation causes cardiac nerve sprouting and consequent arrhythmia. Metoprolol can prevent sympathetic nerve remodeling after myocardial infarction (MI), but the underlying mechanism is unclear. In this study, we evaluated the role of metoprolol in ameliorating sympathetic sprouting. Methods: Rabbits underwent ligation of the coronary artery for MI. MI rabbits received metoprolol or saline for 7 days. Immunohistochemistry was used to measure cardiac nerve sprouting and sympathetic innervations. Nuclear factor-κB (NF-κB) DNA binding activity was analyzed by electrophoretic mobility shift assay. The protein levels of NF-κB p65, inhibitor κBa (IκBa) and nerve growth factor (NGF) were detected by Western blot analysis. The mRNA levels of NGF, interleukin-1ß (IL-1ß) and tumor necrosis factor-a (TNF-a) were examined by quantitative real-time PCR. Results: MI rabbits showed nerve sprouting and sympathetic hyperinnervation. In MI rabbits, as compared with saline treatment, metoprolol reduced NF-κB DNA binding activity and NF-κB p65 level, and increased IκBa level. Moreover, metoprolol downregulated IL-1ß, TNF-a and NGF levels, and reduced the density of sympathetic nerve fibers. Conclusions: Metoprolol ameliorates sympathetic nerve sprouting in rabbits after MI and is associated in part with inhibiting NF-κB activity.

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“…With a decreased HR, the vascular wall has a lower exposure to oscillatory tensile and wall shear stresses [42, 43], decreasing the frequency of the biomechanical load. A reduction in shear and tensile stress is thought to reduce endothelial damage, which leads to a decreased endothelial permeability to inflammatory mediators [42, 43], in line with a decrease in microvascular leakiness and a reduction in macrophage content in the treatment group.…”

Section: Discussionmentioning

confidence: 99%

Heart rate lowering treatment leads to a reduction in vulnerable plaque features in atherosclerotic rabbits

et al. 2017

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ObjectiveTo investigate the effect of a heart rate (HR) lowering agent (Ivabradine) on features of atherosclerotic plaque vulnerability with magnetic resonance imaging (MRI), ultrasound imaging, and histology.Approach and resultsAtherosclerosis was induced in the abdominal aorta of 19 rabbits. Nine rabbits were treated with Ivabradine (17 mg/kg/day) during the entire study period. At week 14, imaging was performed. Plaque size was quantified on contrast-enhanced T1-weighted MR images. Microvascular flow, density, and permeability was studied with dynamic contrast-enhanced MRI. Plaque biomechanics was studied by measuring the aortic distension with ultrasound. After, animals were sacrificed and histology was performed.HR was reduced by 16% (p = 0.026) in Ivabradine-treated animals. No differences in absolute and relative vessel wall beat-to-beat distension were found, but due to the reduction in HR, the frequency of the biomechanical load on the plaque was reduced. Plaque size (MR and histology) was similar between groups. Although microvessel density (histology) was similar between groups, AUC and Ktrans, indicative for plaque microvasculature flow, density, and permeability, were decreased by 24% (p = 0.029) and 32% (p = 0.037), respectively. Macrophage content (relative RAM11 positive area) was reduced by 44% (p<0.001) on histology in Ivabradine-treated animals.ConclusionsHR lowering treatment with Ivabradine in an atherosclerotic rabbit model is associated with a reduction in vulnerable plaque features. The current study suggests that HR reduction may be beneficial for inducing or maintaining a more stable plaque phenotype.

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Increased heart rate and atherosclerosis: Potential implications of ivabradine therapy

Cited by 24 publications

References 34 publications

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Metoprolol-Mediated Amelioration of Sympathetic Nerve Sprouting after Myocardial Infarction

Heart rate lowering treatment leads to a reduction in vulnerable plaque features in atherosclerotic rabbits

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