Comparative Effects Of Carvedilol And Metoprolol In Preventing From Left Ventricular Remodeling And The Expression Of MMP-8/TIMP-1 In Rats After Acute Myocardial Infarction

Objective: To compare the effects of carvedilol and metoprolol in preventing from left ventricular remodeling and the expression of MMP-8/TIMP-1 in rats after acute myocardial infarction .Methods: AMI model was established with the ligation of anterior descending coronary artery in female SD rats. 24 hours after operation,147 survivors were randomly assigned to AMI control(MI,n=43) , metoprolol[20mg/(kg.d)] treatment(B,n=42)group, carvedilol[10mg/(kg.d)] treatment(C,n=42)group, Sham-operated rats(S,n=20) were selected randomly as non-infarction control. According to observation time, each group was subdivide into two subgroups:MI48h group,MI4W group,B48h group,B4w group,C48h group,C4W group,S48h group,S4w group. The final rats number of each subgroup was respectively 11,13,11,11,9,15,8 and 8. Metoprolol was given to group B and Carvedilol was given to group C by gastric gavage at 24h after ligation. The hemodynamics of each group was studied at 48 hours and 4 weeks after ligation and MMP-8,TIMP-1 was analyzed with Western blot.Results:1. Compared with sham-operated 48h group,in MI48h group, systolic blood pressure(SBP), diastolic blood pressure(DBP), mean aortic pressure(MAP) and left ventricular systolic pressure(LVSP) and the maximum rate rise of left ventricular pressure(±dp/dt) were significantly decreased(p<0.05-0.01),while left ventricular end diastolic pressure(LVEDP) was significantly increased(p<0.05);The epression of MMP-8 and TIMP-1 do not change. 2. Compared with sham-operated 4w group, in MI4w group,heart rate,±dp/dt and LVSP were significantly decrease(p<0.05-0.01), while LVEDP is even obviously higher than that of MI48h(p<0.01); Meanwhile the expression of MMP-8 and TIMP-1 are significantly increased(p<0.05-0.01). 3.Compared with MI48h group, SBP,MAP,LVSP,±dp/dt and heart rate are significantly decreased in C48h group,while LVEDP and the expression of MMP-8 and TIMP-1 do not change; There are no changes in B48h group. 4.Compared with MI4w group ,SBP,DBP,MAP , LVEDP and the expressiong of MMP-8 were notable decreased in C4w group(p<0.05-0.01); Only heart rate and LVEDP are significantly decreased in B4w group,but the expression of MMP-8 and TIMP-1 do not change.Conclusions:As abnormal hemodynamics and left ventricular function developed after AMI in rats, the expression of MMP-8 and TIMP-1 are increased. Four weeks treatment of carvedilol could not only improve left ventricular function and hemodynamics, but also inhibit the increase of MMP-8. Metoprolol has equivalent benefieial effect as carvedilol in hemodynamics,left ventricular function but not in inhibition of MMP-8.