Relationship Between Myocardial Apoptosis And Fas/FasL In Heart Failure Rats And Intervention Of Carvedilol

OBJECTIVES: Using congestive heart failure rats as experiental model, to study the ralationsbip between myocardial apoptosis and cardiac Fas/Fash gene expression and their effects on ventricular remodeling and heart function, and to investigate the intervention of carvedilol on heart failure rats.METHODS: The congestive heart failure model was induced by ligating the left descending arteries of Spreague-Dawley(SD) from the myocardial infarction. The rats were randomly divided into four groups:1. heart failure group(n=15)2. metoprolol group(n=15)3, carvedilol group(n=15)4, terazosin group(n=15) was set up as a control one. After 8 weeks of medicince intervention, hemodynamic parameter, left and right ventricular mass index, serum SOD and MDA, myocardial apoptosis and expression of Fas/FasL gene were determined in each group.RESULTS: 1. Compared with sham-operated group, hemodynamic parameters were deteriorated(p＜0.01-0.05), and LVMI and RVMI were risen up by 19.6%和32.7 %, respectively, in heart failure group(p＜0.001-0.01), Under optival mocroscope, myocyte hypetrophy, myocardial cell degeneration, extensive areas of interstitial, inflammatory cell infiltrate were seen inheart failure rats: in heart failure rats, serum SOD activity was descended while MDA was ascended(p＜0.01-0.05): myocardial apoptosis was increased significantly(p＜0.001), and Fas/FasL gene was over-expressed(p＜0.001). In the carvedilol group, LVEDP were descened: and±dp/dtmax decreased(p＜0.01-0.05); LVMI and RVMI was descended, SOD activity was ascended while MDA was descended (p＜0.01-0.05), myocardial apoptosis decreased, and Fas/FasL gene was decreased(p＜0.001).CONCLUSIONS: Cardiomyocytes apoptosis is an important factor which accelerted the ventricalcer hypertrophy and heart failure deterioration. The rised myocardium Fas/FasL was the main reason that stimulated the cardiomyocytes apoptosis and there was a bad cycle between cardiomyocytes apoptosis and heart function's deterioration. Carvedilol can reduce AI. The action may be ralated with the change of Fas/FasL gene expression.