title: Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China. liyuechun1980@sina.com.cn
authors: Li
authors: L
authors: Yue-Chun
authors: Zhang
authors: Z
authors: Teng
authors: Zhou
authors: Z
authors: Na-Dan
authors: Ge
authors: G
authors: Li-Sha
authors: Luo
authors: L
authors: Qin
authors: Guan
authors: G
authors: Xue-Qiang
authors: Lin
authors: L
authors: Jia-Feng
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D003384:Coxsackievirus Infections / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D000077550:Ivabradine; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002227:Carbazoles; D016207:Cytokines; D011412:Propanolamines; D000077261:Carvedilol; D000077550:Ivabradine