Effect of carvedilol on preventing from ventricular remodeling and expression of MMP-8/TIMP-1 in rats after acute myocardial infarction

[Objective]To investigate the effect of carvedilol on Preventing from Ventricular Remodeling and expression of cardiac matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinase(TIMPs) after myocardial infarction in rats.[Methods] Rat models with acute myocardial infarction were established by the ligation of left anterior descending coronary.Twenty-four hours after the operation,Rats were randomly divided into sham-operated group(group S),acute myocardial infarction group(group MI) and carvedilol group(group C).Carvedilol group were treated with carvedilol [10mg/(kg·d)] by gastric gavage,the other two groups were treated with the same amount of distillded water.After 4 weeks of therapy,hemodynamic studies were performed.The heart of rat was fixed and analyzed pathologically.The protein expressions of MMP-8 and TIMP-1 were examined by immunohistochemical analysis.[Results] Compared with sham-operated group,left ventricular(LV) end diastolic pressure(LVEDP),volume(LVV) and weight(LVW) were all significantly increased [(19.9±12.8)mmHg vs(2.2±2.0)mmHg,(0.43±0.11)mL vs(0.91±0.08)mL,(525±62)mg vs(714±64)mg,P0.01];while maximal rate of rise and fall(+ dp /dt) of LV pressure as well as their corrected values(+ dp /dt /LVSP) were significantly reduced(P0.05～0.01) at 4 weeks after AMI,indicating decreased LV function and ventricular remodeling.while the protein expression of MMP-8,TIMP-1 were significantly increased(35.5±0.27 vs 97.6±0.21,43.6±0.24 vs 89.5±0.21,P0.01),After four week carvedilol treatment,the LVEDP,LVV and LVW were significantly reduced [(19.9±12.8)mmHg vs(11.9±9.8)mmHg,P0.01,(0.91±0.08)mL vs(0.73±0.10)mL,P0.05,(714±64)mg vs(623±59)mg,P0.01],while the protein expression of MMP-8 and TIMP-1 were significantly reduced by 27.9%,14.8%(70.4±0.24 vs 97.6±0.21,76.3±0.18 vs 89.5±0.21,P0.01),whereas + dp /dt,+ dp /dt /LVSP were significantly increased(P0.05～0.01) at 4 weeks after AMI.[Conclusions] ① Carvedilol can effectively attenuate ventricular remodeling and improve hemodynamics and LV function after AMI in rats.② Carvedilol may effect the balance of MMP-8/TIMP-1 in Rats After AMI.It is one of causes of alleviating ventricular remodeling.