Comparison of Effects of Ivabradine versus Carvedilol in Murine Model with the Coxsackievirus B3-Induced Viral Myocarditis

Li, Yuechun; Zhang, Teng; Na-Dan, Zhou; Li‐Sha, Ge; Luo, Qin; Guan, Xizhou; Lin, Jiafeng

doi:10.1371/journal.pone.0039394

Cited by 42 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding was supported by Kleinbongard et al who observed in a mouse model that ivabradine reduces infarct size in the absence of heart rate reduction [16]. Additionally, ivabradine was demonstrated to inhibit the production of proinflammatory cytokines such as IL-6 and TNF-alpha, as well as the chemokine MCP-1 [9]. In myocarditis, treatment with ivabradine led to inhibition of myocardial fibrosis, prevention of LV-EF worsening, and improvement of survival [9].…”

Section: Introductionmentioning

confidence: 67%

“…Heart rate reduction results in improved myocardial oxygen supply via a prolonged diastolic filling time, as well as improved ventricular filling. In patients with CHF, ivabradine has a beneficial effect on left ventricular remodeling [9] and survival [10]. …”

Section: Introductionmentioning

confidence: 99%

“…Additionally, ivabradine was demonstrated to inhibit the production of proinflammatory cytokines such as IL-6 and TNF-alpha, as well as the chemokine MCP-1 [9]. In myocarditis, treatment with ivabradine led to inhibition of myocardial fibrosis, prevention of LV-EF worsening, and improvement of survival [9]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Rohm

Kretzschmar

Pistulli

et al. 2016

Journal of Immunology Research

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Rohm

Kretzschmar

Pistulli

et al. 2016

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…The reported improvement in right ventricular function with ivabradine might be clinically significant in ChD HF because right ventricular dysfunction is a challenge in the management of ChD HF 18. Concerning the myocarditis, beneficial pleiotropic effects of ivabradine beyond HR were reported in experimental coxsackievirus B3 myocarditis partially mediated by the inhibition of both the production of proinflammatory cytokines and the synthesis of NO by iNOS 19, 20. Also, ivabradine in chronic viral myocarditis in mice significantly increased the survival rate; attenuated the myocardial lesions and fibrosis; improved the impairment of the LV function; diminished the heart dimension; decreased the production of collagen I and collagen III; reduced the expression of the proinflammatory cytokines tumour necrosis factor alpha and interleukins 1β and 6; and lowered the production of phospho‐p38 MAPK 21.…”

Section: Discussionmentioning

confidence: 99%

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

et al. 2017

View full text Add to dashboard Cite

AimsThe SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients.Methods and resultsSHIFT was a randomized, double‐blind, placebo‐controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta‐blocker. ChD HF presented a poor prognosis (all‐cause mortality at 2 years was ~60%). The mean twice‐daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all‐cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope.ConclusionsChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit–risk profile in ChD HF patients.

show abstract

“…by guest on May 7, 2018 http://hyper.ahajournals.org/ Downloaded from cardiac apoptosis and LV hypertrophy, 35,36 or changes in cardiac protein expression. 37 Such acute mechanical effect of ivabradine is in agreement with previous findings, showing that acute HR reduction has a favorable effect on the depressed wall thickening and increased postsystolic wall thickening during postischemic myocardial stunning.…”

Section: Discussionmentioning

confidence: 99%

Ivabradine Improves Left Ventricular Function During Chronic Hypertension in Conscious Pigs

et al. 2015

View full text Add to dashboard Cite

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...

show abstract

Comparison of Effects of Ivabradine versus Carvedilol in Murine Model with the Coxsackievirus B3-Induced Viral Myocarditis

Cited by 42 publications

References 41 publications

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Impact of Ivabradine on Inflammatory Markers in Chronic Heart Failure

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

Ivabradine Improves Left Ventricular Function During Chronic Hypertension in Conscious Pigs

Contact Info

Product

Resources

About