title: Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol in murine model with coxsackievirus B3-induced viral myocarditis.
abstract: OBJECTIVE
  This study aims to compare the effects of carvedilol and metoprolol in alleviating viral myocarditis (VMC) induced by coxsackievirus B3 (CVB3) in mice.
  
  
  METHODS
  A total of 116 Balb/c mice were included in this study. Ninety-six mice were inoculated intraperitoneally with CVB3 to induce VMC. The CVB3 inoculated mice were evenly divided into myocarditis group (n=32), carvedilol group (n=32) and metoprolol group (n=32). Twenty mice (control group) were inoculated intraperitoneally with normal saline. Hematoxylin and eosin staining and histopathologic scoring were used to investigate the effects of carvedilol and metoprolol on myocardial histopathologic changes on days 3 and 5. In addition, serum cTn-I levels, cytokine levels and virus titers were determined using chemiluminescence immunoassay, enzyme-linked immunosorbent assay and plaque assay, respectively, on days 3 and 5. Finally, the levels of phosphorylated p38MAPK were studied using immunohistochemical staining and Western blotting on day 5.
  
  
  RESULTS
  Carvedilol had a stronger effect than metoprolol in reducing the pathological scores of VMC induced by CVB3. Both carvedilol and metoprolol reduced the levels of cTn-I, but the effect of carvedilol was stronger. Carvedilol and metoprolol decreased the levels of myocardial pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokine, with the effects of carvedilol being stronger than those of metoprolol. Carvedilol had a stronger effect in reducing myocardial virus concentration compared with metoprolol. Carvedilol was stronger than metoprolol in decreasing the levels of myocardial phosphorylated p38MAPK.
  
  
  CONCLUSIONS
  In conclusion, carvedilol was more potent than metoprolol in ameliorating myocardial lesions in VMC, probably due to its stronger modulation of the balance between pro- and anti-inflammatory cytokines by inhibiting the activation of p38MAPK pathway through β1- and β2-adrenoreceptors.
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, PR China; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, PR China. Electronic address: chumpwz@126.com.
authors.forename: Maoping
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, PR China. Electronic address: wd4014@126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029822:Enterovirus B, Human / Q000472:pathogenicity; D008790:Metoprolol / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D011412:Propanolamines / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D016207:Cytokines; D011412:Propanolamines; D000077261:Carvedilol; D048051:p38 Mitogen-Activated Protein Kinases; D008790:Metoprolol
keywords: Carvedilol; Coxsackievirus B3; Inflammation; Metoprolol; Viral myocarditis