Mechanisms Of Metoprolol To Prevent The Myocardial Dysfunction From Coronary Microembolization

Objective To evaluate the effect ofβ-adrenergic blocker- metoprolol on myocardial inflammatory cytokines expression and the myocardial function in rats after coronary microembolization.Methods 42μm microspheres were injected into the left ventricle during 10 seconds occlusion of the ascending aorta to make a rat model of coronary microembolization.Rats were randomly divided into sham group,coronary microembolization group(CME)and metoprolol treatment group(CME-B).Five time points(3hour,6hour,12hour,24hour and 4week)were chosen to evaluate myocardial inflammation and heart function in each group.The therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks were studied on the rat modle of coronary microembolization. Myocardial inflammation was studied by accounting the number of infiltrated inflammatory cells in myocardium and analyzing the myocardial inflammatory cytokines such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and the anti-inflammatory cytokine interleukin- 10(IL-10).Myocardial function was detected by echocardiography.Results The levels of TNF-α,IL-1β,IL-10 in CME group were markedly increased comparing to S group at 3h,6h,12h and 24h time points(all P＜0.05),whose peak levels showed up at the 12h time point but markedly decreased at the 24h time point.No differences had been found between these two groups at the 4w time point(all P＞0.05).The levels of TNF-α,IL-1βin CME-B group were markedly lower than CME group,but the levels of IL-10 were markedly higher than CME group(all P＜0.05).Echocardiography showed that the left ventricular ejection(LVEF)of CME group was markedly decreased at each time point comparing to S group.No differences of EF existed between CME-B group and CME group at 3h,6h time point(all P＞0.05)except the 12h,24h and 4w time point at which the EF of CME-B group were markedly higher than CME group(all P＜0.05).There was a significantly negative correlation between the expression ofTNF-αmRNA and the EF at 3h,6h,12h,24h time point of CME group,but no correlation existed at the 4w time point.The infarct sizes and the inflammatory cells infiltration in CME group were not markedly different comparing to CME-B group(all P＞0.05).No microinfarction areas and inflammatory cells infiltration were found in S group.Conclusions The levels of TNF-α,IL-1β,IL-10 in myocardium are all increased significiently after coronary microembolization and this play an important role in the myocardial dysfunction.Metoprolol can markedly improve the myocardial function by decreasing inflammatory cytokines and increasing anti-inflammatory cytokines in myocardium.