Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in rats: role of toll-like receptor 4 and β-arrestin 2

C.-C. Liu, Y. Huang, J.-H. Zhang, Y. Xu, C.-H. Wu

Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, PR China. yanxucn@163.com

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• Cardiology

OBJECTIVES: 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.

MATERIALS AND 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.

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