Experimental Study On Role Of Valsartan To Cardiomyocyte Apoptosis And Ventricular Remodeling In Rats With Congestive Heart Failure

Objective (1) To investigate the role of cardiomyocyte apoptosis andventricular remodeling in the progress of heart failure by experiments of heart failure model in rats. (2) To explore the mechanism and evaluate the therapeutic effects of angiotensin II type 1 receptor (AT1) antagonism on rats with congestive heart failure by observing the changes of cardiomyocyte apoptosis and ventricular remodeling induced by using of valsartan.Methods Pathological models of congestive heart failure (CHF) wereestablished by constriction of abdominal aorta of rats partly. Then they were divided randomly into 2 groups and each group had 10 rats. One was valsartan treated group, the other was named as heart failure group. Another 10 corresponding Wistar-Kyoto rats were recruited as sham-operated. That is, they were operated as these two groups except abdominal aortic banding. The rats hi valsartan group began to be treated with daily 15mg/kg valsartan by gavage at the end of 10th week after operation, while the other rats were administered equal volume of distilled water respectively by the same way. Six weeks later, all the rats were killed, and (1) all the left ventricular muscle weight (LVW) were measured respectively to calculate the left ventricular weight index (LVMT). (2) It was performed to analyze the collagen concentration by measuring left ventricular hydroxyproline content. (3) Observed the pathological morphological change of cardiac myocyte and the degree of myocardial interstitial fibrosis with light microscopy after cardiac tissue were handled by H.E or collagen V.G staining. (4)Compared the difference of electrophoresis pattern of myocardial apoptosis among the three groups as the method of assessing apoptosis in myocardium.Result (1) The left ventricular weight index (LVWI): the left ventricular weightindex of heart failure group (4.08±0.21 ) increased significantly contrast to sham-operated group (2.32±0.14 p<0.01 ) or valsartan treating group (2.91±0.32p<0.01) . While the difference between valsartan treating group and sham-operated group still existed (p<0.05). (2) The left ventricular collagen content (LVCC) : the left ventricular collagen content of heart failure group (7.91±0.21 ug/mg) is more than the sham-operated group (5.37±0.13 ug/mg p<0.01) or valsartan treating group (5.89± 0.18 ug/mg p<0.01) . There is still obviously difference between valsartan treated and sham-operated group (p<0.05), although the item was clearly decreased in the treating group contrast to heart failure group. (3) After H.E or collagen staining, the pathomorphology photos showed ventricular remodeling including myocardial cells hypertrophy and myocardial interstitial fibrosis with rearrangement and slippage of muscle fibers in the heart failure group. Otherwise in the rats of valsartan treating group, the situation was significantly improved, there was less myofibrillae and less collagen fibrillae, but still didn't recover to the level of the sham-operated rats.(4)There appeared typical "DNA Ladder" in heart failure and valsartan treating groups by agarose gel electrophoresis but the sham-operated group didn't show the phenomenon. And the "DNA Ladder" in valsartan treating group was dimmer and fainter than the heart failure group.Conclusion (1) The results suggest that cardiomyocyte apoptosis andventricular remodeling take an important role in the development of heart failure. (2) The results also indicate that valsartan can effectively decrease myocardial apoptosis and regress ventricular remodeling at the same time. (3) It is suggested that angiotensin II receptor antagonism are effective in treatment of heart failure and have a good prognosis. The mechanism may be related to decrease myocardial apoptosis and reverse ventricular remodeling.