Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis

Elevated heart rate is associated with increased cardiovascular morbidity. The selective I(f) current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects...

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Bibliographic Details
Published in:PloS one 2012-06, Vol.7 (6), p.e39394-e39394
Main Authors: Yue-Chun, Li, Teng, Zhang, Na-Dan, Zhou, Li-Sha, Ge, Qin, Luo, Xue-Qiang, Guan, Jia-Feng, Lin
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Adrenergic beta-Antagonists - therapeutic use
Adrenergic receptors
Analysis
Angiogenesis
Animal models
Animals
Apoptosis
Apoptosis - drug effects
Arteriosclerosis
Atherosclerosis
Benzazepines - pharmacology
Benzazepines - therapeutic use
Beta blockers
Biology
Blood pressure
Carbazoles - pharmacology
Carbazoles - therapeutic use
Cardiology
Cardiomyocytes
Carvedilol
Collagen
Congestive heart failure
Coxsackievirus infections
Coxsackievirus Infections - complications
Coxsackievirus Infections - physiopathology
Coxsackievirus Infections - virology
Coxsackieviruses
Cytokines
Cytokines - metabolism
Disease Models, Animal
Enterovirus B, Human
Heart
Heart - drug effects
Heart - physiopathology
Heart failure
Heart rate
Heart Rate - drug effects
Inflammation
Interleukin 6
Ivabradine
Laboratory animals
Lesions
Male
Malondialdehyde
Medicine
Mice
Monocyte chemoattractant protein 1
Morbidity
Muscle contraction
Myocardial Contraction - drug effects
Myocarditis
Myocarditis - drug therapy
Myocarditis - physiopathology
Myocarditis - virology
Myocardium - metabolism
Noradrenaline
Norepinephrine
Oxidative stress
Oxidative Stress - drug effects
Propanolamines - pharmacology
Propanolamines - therapeutic use
Reduction
Superoxide dismutase
Superoxides
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Vascular endothelial growth factor
Ventricle
Viral infections
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Summary:Elevated heart rate is associated with increased cardiovascular morbidity. The selective I(f) current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects by decreasing cardiac proinflammatory cytokines and inhibiting peroxidants and collagen accumulation in atherosclerosis or congestive heart failure. However, the effects of ivabradine in the setting of acute viral myocarditis and on the cytokines, oxidative stress and cardiomyocyte apoptosis have not been investigated. The study was designed to compare the effects of ivabradine and carvedilol in acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of ivabradine and carvedilol (a nonselective β-adrenoceptor antagonist) on myocardial histopathological changes, cardiac function, plasma noradrenaline, cytokine levels, cardiomyocyte apoptosis, malondialdehyde and superoxide dismutase contents were studied. Both ivabradine and carvedilol similarly and significantly reduced heart rate, attenuated myocardial lesions and improved the impairment of left ventricular function. In addition, ivabradine treatment as well as carvedilol treatment showed significant effects on altered myocardial cytokines with a decrease in the amount of plasma noradrenaline. The increased myocardial MCP-1, IL-6, and TNF-α. in the infected mice was significantly attenuated in the ivabradine treatment group. Only carvedilol had significant anti-oxidative and anti-apoptoic effects in coxsackievirus B3-infected mice. These results show that the protective effects of heart rate reduction with ivabradine and carvedilol observed in the acute phase of coxsackievirus B3 murine myocarditis may be due not only to the heart rate reduction itself but also to the downregulation of inflammatory cytokines.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039394