The Beneficial Effects Of Carvedilol On Cardiomyocyte Apoptosis And Related Gene Expression After Acute Myocardial Infarction In Rats

Objective To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and ventricular remodeling after acute myocardial infarction (AMI) in rats.Methods 126 female wistar rats were randomly made into AMI model with the ligation of anterior descending coronary artery. The 79 survivors were randomly assigned to carvedilol (1 Omg/kg/d) treatment (C, n=37) and AMI control (MI, n=42) group after 24 hours of ligation. Each group was reassigned to 72-hour and 5-week subgroups according to the observation time, that is:MI72h(n=12) and MI 5w(n=14) subgroups, C72h(n=12) and C5w subgroups. Sham-operated (S, n=27)group was selected randomly, and also reassigned to S72h(n=10) and S5w(n=10) subgroups Carvedilol was given to each treatment group. Testing cardiomyocyte apoptosis with TUNEL and DNA ladder. To detect caspase-3, bcl-2 and bax with immunohistochemistry. Echocardiographic evaluated the cardiac function.Results (1) Compared with MI72h subgroup, myocyte apoptosis rate (MAR) had no significantly changes in infarction, border and non-infarcted area(P>0.05)in C72h subgroups. MAR was significantly decreased (P<0.05) only in infarction and border area, and no change was found of MAR in non-infarcted area(P> 0.05) in C5w subgroups compared with MI5w subgroup. (2) Compared with MI72h, MI5w subgroups, no change of caspase-3 expression was found in the three areas mentioned above in the C72h and C5w subgroups.(3) Compared with MI72h, MI5w subgroups, bcl-2 expression was significantly increased in infarction and border areas in C72h, bcl-2 expression had no change in myocytes of infarction, border and non-infarcted areas in C5w. (4) Only in infarction area, bax expression was significantly decreased in C5w subgroups, in myocytes of the other areas, no change of bax expression was found in C72h and C5w subgroups.(3) Compared with S72h subgroup. Ejection fraction (EF) was significantly decreased in C72h and C5w subgroups but Left ventricular diastolic diameter (LVEDD) was no significantly change. Compared with C5w subgroup, EF was significantly decreased, LVEDD was significantly increased in MI5w subgroup. Compared with S5w subgroup, EF was significantly decreased but LVEDD was no significantly change in C5w subgroup.Conclusions (1) Early after AMI in rats, carvedilol could not reduce MAR in infarction area; treatment with carvedilol 5 weeks later, it could reduce MAR in infarction, border and non-infarcted areas. (2) Treatment with carvedilol could not affected caspase-3 expression in myocytes. (3) Treatment with carvedilol, bcl-2 expression was increased in infarction and border areas early after AMI in rats. (4) Carvedilol could reduce bax expression only in myocytes of infarcted area 5 weeks later. (4) The early stage of AMI, EF was significantly decreased, but LVEDD was no significantly change.5w later. EF was significantly decreased, and LVEDD was significantly increased. Carvedilol maybe delay the ventricular remodeling.