Carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion

IntroductionMyocardial 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.MethodsThirty-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.ResultsCompared 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, β-catenin, and γ-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, β-catenin and γ-catenin levels (all P > 0.05).ConclusionPretreatment 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 β-blocking action.