Anti-inflammatory effects of ivabradine in patients with acute coronary syndrome: a pilot study

Domínguez‐Rodríguez, Alberto; Consuegra-Sánchez, Luciano; Blanco-Palacios, Gabriela; Abreu-González, Pedro; Sanchez-Grande, Alejandro; Bosa‐Ojeda, Francisco; Kaski, Juan Carlos

doi:10.1016/j.ijcard.2012.04.076

Cited by 22 publications

(21 citation statements)

References 14 publications

(10 reference statements)

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“…Also, serum levels of CK-MB, hs-CRP and cTnI and infarct size % in this group were significantly lower than that of the control MI group. These results are consistent with that obtained by Dedkov et al [40] , Dominguez-Rodriguez et al [41] , Heusch et al [42] , Monnet et al [43] and Vilaine et al [44] . The mechanism of the cardioprotective effect of ivabradine could be self-explained in the present study by its significant HR reduction, significant decrease of the apoptotic factor Bax and significant increase of the antioxidant markers SOD& GSH.…”

Section: Shireen Sami Mahmoud ; Et Al…supporting

confidence: 92%

Protective Effects of Ivabradine (Alone and Combined With Atenolol or Enalapril) on Experimentally-Induced Acute Myocardial Infarction in Albino Rats

Mahmoud

Shehata

Moustafa

et al. 2017

Zagazig University Medical Journal

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Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Deaths are mostly attributable to coronary artery disease (CAD). Ivabradine, a pure heart rate lowering agent, acts by inhibiting the pacemaker I f current in the sinoatrial node. It can be used for treatment of heart failure and stable angina with the main drugs for CVD. Objectives: To determine the cardioprotective effects of ivabradine pretreatment alone and in combination with each of atenolol and enalapril on acute myocardial infarction (MI) in rats. Materials & Methods: Eighty four rats were divided into seven groups (12 rats each): Group 1: sham-operated group; Group 2: control (untreated) MI group; Group 3: ivabradine-pretreated group; Group 4: atenolol-pretreated group; Group 5: enalaprilpretreated group; Group 6: ivabradine and atenolol-pretreated group; and Group 7: ivabradine and enalapril-pretreated group. Rats received drugs orally by gavage daily for 6 days. On the sixth day, acute MI was induced by persistent complete left coronary artery ligation. The parameters studied were mean arterial blood pressure, ECG changes (heart rate, ST height and T-wave voltage), serum levels of creatine kinase MB isoenzyme (CK-MB), cardiac troponin-I (cTnI), high-sensitivity Creactive protein (hs-CRP) and N-terminal pro-brain-type natriuretic peptide (NTproBNP), tissue levels of superoxide dismutase (SOD), reduced glutathione (GSH), Bcl-2-associated X protein (Bax) and the % of infarct size of the left ventricle.

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Section: Shireen Sami Mahmoud ; Et Al…supporting

confidence: 92%

Protective Effects of Ivabradine (Alone and Combined With Atenolol or Enalapril) on Experimentally-Induced Acute Myocardial Infarction in Albino Rats

Mahmoud

Shehata

Moustafa

et al. 2017

Zagazig University Medical Journal

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“…Several experimental studies (Sajadieh et al, 2004; Fox et al, 2008; Perret-Guillaume et al, 2009) have demonstrated that inflammation has a close relationship with HR. With an increased HR, inflammation would be aggravated, and the cardiovascular death rate and hospital admissions because of HF are significantly increased (Sajadieh et al, 2004; Fox et al, 2008; Dominguez-Rodriguez et al, 2012; O Hartaigh et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Ivabradine in Preventing Progression from Viral Myocarditis to Dilated Cardiomyopathy

Guang-Yi

Li‐Sha

et al. 2016

Front. Pharmacol.

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To study the beneficial effects of ivabradine in dilated cardiomyopathy (DCM) mice, which evolved from coxsackievirus B3-induced chronic viral myocarditis. Four-to-five-week-old male balb/c mice were inoculated intraperitoneally with coxsackievirus B3 (Strain Nancy) on days 1, 14, and 28. The day of the first virus inoculation was defined as day 1. Thirty-five days later, the surviving chronic viral myocarditis mice were divided randomly into two groups, a treatment group and an untreated group. Ivabradine was administered by gavage for 30 consecutive days in the treatment group, and the untreated group was administered normal saline. Masson’s trichrome stain was used to evaluate the fibrosis degree in myocardial tissue. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), collagen I, collagen III and p38-MAPK signaling pathway proteins were detected by Western blot. Electrocardiogram was used to investigate the heart rate and rhythm. The thickness of the ventricular septum and left ventricular posterior wall, left ventricular end diastolic dimension, left ventricular end systolic dimension, left ventricular ejection fractions and fractional shortening were studied by echocardiography. Compared with the untreated chronic viral myocarditis mice, ivabradine significantly increased the survival rate, attenuated the myocardial lesions and fibrosis, improved the impairment of the left ventricular function, diminished the heart dimension, decreased the production of collagen I and collagen III, reduced the expression of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, and lowered the production of phospho-p38 MAPK. The findings indicate the therapeutic effect of ivabradine in preventing the progression from viral myocarditis to DCM in mice with chronic viral myocarditis induced by coxsackievirus B3, is associated with inhibition of the p38 MAPK pathway, downregulated inflammatory responses and decreased collagen expression. Ivabradine appears a promising approach for the treatment of patients with viral myocarditis.

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“…Whether these effects result from heart rate reduction or represent a heart rate independent mechanism needs to be further investigated. The RIVERA study is one pilot study which will analyze anti-inflammatory effects of ivabradine in more detail [33]. However, this study is designed for a population of patients with acute coronary syndrome.…”

Section: Discussionmentioning

confidence: 99%

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Rohm

Kretzschmar

Pistulli

et al. 2016

Journal of Immunology Research

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Background. Inflammation plays a crucial role in the progression of chronic heart failure (CHF). Ivabradine is known to reduce the morbidity and mortality of patients with CHF under certain conditions. Beyond the reduction of heart rate, only limited knowledge exists about potential anti-inflammatory effects of ivabradine that might contribute to its benefit in CHF. Thus, the present study aimed to investigate the effect of ivabradine on systemic inflammation. Methods. In the present study, 33 patients with CHF due to dilated, ischemic, and hypertensive cardiomyopathy were treated with ivabradine according to the guidelines of the European Society of Cardiology (ESC). A number of circulating dendritic cells as well as inflammatory mediators were investigated using FACS analysis and ELISA, respectively, before and during ivabradine therapy. Results. Treatment with ivabradine resulted in a significant improvement of CHF symptoms as well as an increase in left ventricular ejection fraction. Moreover, ivabradine treatment led to a significant reduction of TNF-alpha (TNF-α) serum levels and a reconstitution of circulating dendritic cells which are known to be reduced in patients with CHF. Conclusion. We show that treatment with ivabradine in patients with CHF resulted in an improvement of HF symptoms and ejection fraction as well as a normalization of inflammatory mediators.

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Anti-inflammatory effects of ivabradine in patients with acute coronary syndrome: a pilot study

Cited by 22 publications

References 14 publications

Protective Effects of Ivabradine (Alone and Combined With Atenolol or Enalapril) on Experimentally-Induced Acute Myocardial Infarction in Albino Rats

Protective Effects of Ivabradine (Alone and Combined With Atenolol or Enalapril) on Experimentally-Induced Acute Myocardial Infarction in Albino Rats

The Protective Effects of Ivabradine in Preventing Progression from Viral Myocarditis to Dilated Cardiomyopathy

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

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