title: Carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion.
abstract: BACKGROUND
  Myocardial no-reflow, has been associated with alterations in endothelial junctions, which is regulated in part by endothelial dysfunction. Carvedilol is an alpha1 and nonselective beta-adrenergic receptor antagonist with antioxidative properties known to protect endothelial function. Therefore, we hypothesized that carvedilol might also have protective effects on myocardial no-reflow and endothelial junctions.
  
  
  METHODS
  Thirty-two mini-swines were randomized into 4 study groups: 8 in control, 8 pretreated with carvedilol (1 mg/kg/d) for 3 days, 8 in propranolol (nonselective beta-adrenergic receptor antagonist)-pretreated for 3 days and 8 in sham-operated. Acute myocardial infarction and reperfusion model was created with 3 h occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. Coronary ligation area (LA) and area of no-reflow were determined with both myocardial contrast echocardiography (MCE) in vivo and pathological means (Path). Myocardial vascular endothelial (VE)-cadherin, beta-catenin and gamma-catenin were assessed by immunoblot.
  
  
  RESULTS
  Compared with the control group, carvedilol significantly improved ventricular function, increased coronary blood flow from 50.6+/-3.1% to 72.1+/-3.8% of the baseline at 1 h of reperfusion (P<0.01), decreased area of no-reflow (MCE: from 78.5+/-4.5% to 24.9+/-4.1%, Path: from 82.3+/-1.9% to 25.8+/-4.3% of LA respectively, all P<0.01), reduced necrosis area from 98.5+/-1.3% to 74.4+/-4.7% of LA (P<0.05). The levels of VE-cadherin, beta-catenin, and gamma-catenin in the reflow myocardium were significantly greater in the carvedilol group (all P<0.05). However, propranolol failed to significantly modify area of no-reflow, VE-cadherin, beta-catenin and gamma-catenin levels (all P>0.05).
  
  
  CONCLUSIONS
  Pretreatment with carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion. The beneficial effect of carvedilol was not due to its beta-blocking action.
authors.affiliation: Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Zhao
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Yang
authors.forename: Shijie
authors.initials: S
authors.lastname: you
authors.forename: Chuanjue
authors.initials: C
authors.lastname: Cui
authors.forename: Runlin
authors.initials: R
authors.lastname: Gao
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D018890:Chemoprevention / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011412:Propanolamines / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D000317:Adrenergic alpha-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol