Heart Rate Reduction Induced by the If Current Inhibitor Ivabradine Improves Diastolic Function and Attenuates Cardiac Tissue Hypoxia

Fang, Yuehui; Debunne, Manuelle; Vercauteren, Magali; Bråkenhielm, Ebba; Richard, Vincent; Lallemand, Françoise; Henry, Jean‐Paul; Mulder, Paul; Thuillez, Christian

doi:10.1097/fjc.0b013e31823e5e01

Cited by 45 publications

(56 citation statements)

References 37 publications

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“…This beneficial impact of ivabradine on diastolic dysfunction was recently corroborated in another model. 80 In a mouse model of angiotensin II-induced HF, 81 both ivabradine and metoprolol led to a similar reduction in HR, but only ivabradine led to a significant improvement in LV systolic and diastolic function. This effect was associated with reductions in cardiac hypertrophy, fibrosis, inflammation, and apoptosis.…”

Section: Hcn Channels and Hf Hcn Blockade In Animal Modelsmentioning

confidence: 99%

New Therapeutic Targets in Cardiology

Roubille

Tardif

2013

Circulation

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Section: Hcn Channels and Hf Hcn Blockade In Animal Modelsmentioning

confidence: 99%

New Therapeutic Targets in Cardiology

Roubille

Tardif

2013

Circulation

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“…25 Ivabradine has several advantages on other bradycardic agents as it modifies neither LV contractility 8 nor mean ventricular stress during ejection 12 and preserves ventricular relaxation unlike β-blockers. 12,26,27 HR reduction exhibits also powerful antiischemic action [28][29][30][31] and increases diastolic coronary perfusion time. 9 In this study, HR reduction with ivabradine decreased isovolumic contraction and relaxation times both in resting conditions and under dobutamine, contributing to favor LV filling and preserve ejection.…”

Section: Discussionmentioning

confidence: 99%

“…HR reduction exhibits also powerful antiischemic action [28][29][30][31] and increases diastolic coronary perfusion time.…”

Section: 2627mentioning

confidence: 99%

Ivabradine Improves Left Ventricular Function During Chronic Hypertension in Conscious Pigs

et al. 2015

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In the normal heart, reduction of isovolumic contraction and relaxation durations is a physiological response to increase in heart rate (HR). This allows the heart to maintain a constant and controlled balance between the different phases of cardiac cycle for favoring both left ventricular (LV) ejection and filling. 1,2 We previously evaluated LV function during chronic hypertension and hypertrophy induced by continuous infusion of angiotensin II in pigs. 3 Although no clinical signs of heart failure were present, we observed early and simultaneous maladaptive LV responses to chronotropic and inotropic stimuli that altered diastolic filling time. The maladaptive LV responses displayed as 1 failure of isovolumic contraction and relaxation durations to reduce while HR accelerated and 2 abnormally blunted isovolumic contraction and relaxation responses to dobutamine infusion. In hypertrophied hearts, there is abnormal LV subendocardial blood flow and limited coronary reserve that might fail to meet myocardial oxygen consumption, leading to myocardial ischemia and dysfunction. [4][5][6] These observations led us to consider a role of increased HR in the deterioration of LV function during chronic hypertension.Accordingly, we investigated the effects of acute selective HR reduction with the I f -channel blocker ivabradine 7 on LV dysfunction in our chronic hypertensive pig model (continuous angiotensin II infusion) 3 because this drug has the advantage that it does not modify atrioventricular or intraventricular conduction, inotropy, and lusitropy in animals and humans. [8][9][10][11] Reduction in HR could facilitate diastolic filling by prolonging the diastolic period, 12,13 improving arterioventricular coupling, 14 or reducing myocardial ischemia. 15,16 Here, we hypothesized that selective HR reduction with ivabradine could restore a normal balance between the different phases of the cardiac cycle by normalizing isovolumic contraction and relaxation times. We also investigated whether ivabradine Abstract-During chronic hypertension, increases in heart rate (HR) or adrenergic stimulation are associated with maladaptive left ventricular responses as isovolumic contraction and relaxation durations failed to reduce, impeding filling. We, therefore, investigated the effects of acute selective HR reduction with ivabradine on left ventricular dysfunction during chronic hypertension. Accordingly, chronically instrumented pigs received angiotensin II infusion during 4 weeks to induce chronic hypertension. Left ventricular function was investigated while angiotensin II infusion was stopped. A single intravenous dose of ivabradine was administered at days 0 and 28. Dobutamine infusion was also performed. HR was increased at day 28 versus day 0. Paradoxically, both isovolumic contraction and relaxation times failed to reduce and remained unchanged (57±3 versus 58±3 ms and 74±3 versus 70±3 at day 28 versus day 0, respectively). At day 28, ivabradine significantly reduced HR by 27%. Concomitantly, abnormal ventricular response...

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“…Postulated mechanisms of benefit from ivabradine-mediated heart rate reduction include decreased myocyte ischemia, improving the balance between myocardial oxygen (and energy) supply and demand; this effect is attributable not only to reduction in demand but also to increased supply caused by lengthening duration of diastole during which coronary flow occurs, and lack of negative lusitropy (relaxation, an active process that is inhibited by ischemia and also by beta blockade) reducing impedance to coronary flow relative to beta blockade [12]; other data suggest that use of the drug also increases endothelial cell proliferation, endothelial nitric oxide synthase (eNOS) activity, and increased collateral function [13].…”

Section: Ivabradinementioning

confidence: 99%

Role of New Therapies in Reducing Mortality and Major Morbidity in Patients with Systolic Heart Failure

Yurevich¹,

Borer²

2017

The Role of the Clinical Cardiac Electrophysiologist in the Management of Congestive Heart Failure

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Though heart failure therapies, particularly for systolic heart failure, have developed rapidly and markedly during the past four decades, a need for additional relief persists and is progressively being met. Two new drugs have been approved for marketing in the United States within the past two years, and two other glucose lowering therapies for diabetes appear to have efficacy for heart failure as well. In addition, device therapy for heart failure has progressed markedly during the past 5 years, particularly in refinements of the indications and applications of devices to minimize symptoms and hospitalizations and to maximize survival. This chapter will outline these recent developments.

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Heart Rate Reduction Induced by the If Current Inhibitor Ivabradine Improves Diastolic Function and Attenuates Cardiac Tissue Hypoxia

Cited by 45 publications

References 37 publications

New Therapeutic Targets in Cardiology

New Therapeutic Targets in Cardiology

Ivabradine Improves Left Ventricular Function During Chronic Hypertension in Conscious Pigs

Role of New Therapies in Reducing Mortality and Major Morbidity in Patients with Systolic Heart Failure

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