OBJECTIVE: The aim of study was to explore the effects of early beta-adrenergic blockade-metoprolol treatment on myocardial inflammatory cytokine expression and heart function in rats after acute myocardial infarction (AMI). METHODS: The therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks (according to the protocol of CCS-2) were studied by the rat model of AMI. Myocardial inflammation was examined by taking account of the number of lymphocytes infiltrated in the myocardium and analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1beta, 6 and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. RESULTS: The levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in AMI group were markedly elevated compared to sham rats (P < 0.01) and the cytokines principally excreted by cardiac myocytes. After 4 weeks therapy, metoprolol reduced the production of TNF-alpha and IL-1beta and increased IL-10 levels (P < 0.05) in cardiac myocytes, but had no effect on the number of lymphocytes infiltrated in myocardium. Echocardiography showed that metoprolol markedly improved left heart function (P < 0.05). CONCLUSION: Early metoprolol treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One immunopharmacologic mechanism underlying the beneficial effects of beta-adrenergic blockade may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.
OBJECTIVE: The aim of study was to explore the effects of early beta-adrenergic blockade-metoprolol treatment on myocardial inflammatory cytokine expression and heart function in rats after acute myocardial infarction (AMI). METHODS: The therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks (according to the protocol of CCS-2) were studied by the rat model of AMI. Myocardial inflammation was examined by taking account of the number of lymphocytes infiltrated in the myocardium and analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1beta, 6 and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function. RESULTS: The levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in AMI group were markedly elevated compared to sham rats (P < 0.01) and the cytokines principally excreted by cardiac myocytes. After 4 weeks therapy, metoprolol reduced the production of TNF-alpha and IL-1beta and increased IL-10 levels (P < 0.05) in cardiac myocytes, but had no effect on the number of lymphocytes infiltrated in myocardium. Echocardiography showed that metoprolol markedly improved left heart function (P < 0.05). CONCLUSION: Early metoprolol treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One immunopharmacologic mechanism underlying the beneficial effects of beta-adrenergic blockade may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.