title: Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in rats: role of toll-like receptor 4 and β-arrestin 2.
abstract: OBJECTIVE
  To assess the beneficial effect of carvedilol treatment on infarct myocardium and the relation to the expression of nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), and β-arrestin 2.
  
  
  METHODS
  Rat myocardial infarction (MI) model was produced by ligating the left anterior descending coronary artery. Forty-eight rats were randomized to the following groups before surgery: sham-operated group (n=8), MI group (n=10), and three carvedilol-treatment groups (n=30, 2 mg/kg, 10 mg/kg and 30 mg/kg).
  
  
  RESULTS
  Four days after MI, carvedilol treatment could ameliorate left ventricular dysfunction by inhibiting the MI-induced increase of left ventricular end diastolic pressure and the decrease of left ventricle end systolic pressure and the changes to their maximum rates (+dp/dtmax and -dp/dtmax). Histological examination showed that carvedilol attenuated myocardium necrosis and inflammatory cell infiltration. In parallel, the treatment also suppressed the expression of NF-κB and TLR4 induced by MI, but increased the expression of β-arrestin 2.
  
  
  CONCLUSIONS
  These results indicate that short term administration of carvedilol could improve early cardiac dysfunction in a rat model of MI. This beneficial effect may be attributed to inhibit the expression of NF-κB and TLR4, but induce the expression of β-arrestin 2 in the infarct region of the myocardium, which would suppress inflammation.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, PR China. yanxucn@163.com.
authors.forename: C-C
authors.initials: CC
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: J-H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: C-H
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605257:Arrb2 protein, rat; D019390:Arrestins; D002227:Carbazoles; D002316:Cardiotonic Agents; D052002:NF-kappa B p50 Subunit; D011412:Propanolamines; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D000077261:Carvedilol