Research Of The Role Of Cardiomyocytes Apoptosis During The Development Of Congestive Heart Failure After Myocardium Infarction

There are a lot of evidences show that cardiomyocytes apoptosis is a normal pathologic phenomenon of the diseases such as MI, virus myocarditis and CHF in recent years. But the significance of apoptosis during the progress of congestive heart failure after myocardial infarction isn't clear now. And we believe the research of cardiomyocytes apoptosis during the progress of CHF after MI will help us to find new therapeutic method of CHF. And so do the research about facilitating factor of cardiomyocytes apoptosis.ACEI is the basic drug for CHF patients. It can prolong the patients'remote survival rate if they use ACEI persistently. ATR1A is the replacing drug of patients who can't tolerate the side effect of ACEI. We don't know the two drugs' influence to cardiomyocytes apoptosis and the connection between cardiomyocytes apoptosis and left ventricular remodeling and the improving of heart failure when it is used for CHF patients now. Objective: To understand (1) The affection of TNF-a in myocardium to cardiomyocytes apoptosis. (2) The connection of cardiomyocytes apoptosis and left ventricular remodeling and change of heart function after MI. (3) The affection to cardiomyocytes apoptosis when ACEI or ATR1A is used to therapy CHF, and its connection with left ventricular remodeling and heart function improvement.Method: (1) We made rat MI model through left anterior decending coronary artery ligation, and then the MI rats were devided into MI groups, Enalapril groups, Losartan groups. There was a sham-operated group besides. (2) The rats' LV/BW was measured and regarded as the index of left ventricular remodeling. (3) Heart function was measured at 7, 14, 28 and 56 days after operation. (4) The level of myocardium TNF-a was determined through radioimmunoassay method. (5) TUNEL staining was performed to determine the rats' cardiomyocytes apoptosis level after MI Result: (1) There were apoptotic myocytes in the border zones andremote area of MI. The apoptotic coefficience in the border zones dropped from 7.9% at 7d to 4.0% at 56d and it rised from 1.6% to 4.1% in remote area of MI. Enalapril or Losartan decreased the apoptotic myocytes significantly and there was no significant difference between two drugs during the later stage after MI. (2) The myocardium TNF-a level and LV/BW rised significantly after MI and it lowed significantly when Enalapril or losartan was given to rats. The apoptotic coefficience in remote area of MI was significantly correlated with the level of TNF-a and LV/BW(r=0.828, 0.637, p<0.05). TNF-a was a stimulative factor of apoptosis. The heart fuction(lvsp ,dp/dtmax,lvdp,dp/dtmin) deteriorated as the apoptotic coefficience rised. (3)Losartan and Enalapril also decreased apoptotic coefficience and TNF-a level, and then inhibited ventricular remodeling and improved heart function, there was no significant difference between the two drugs yet.Conclusion: (1) Cardiomyocytes apoptosis is an important factor which accelerated the ventricular hypertrophy and heart failure deterioration after MI. (2) The rised myocardium TNF-a was the main reason that stimulated the cardiomyocytes apoptosis after MI, and there was a bad cycle between cardiomyocytes apoptosis and heart function's deterioration. (3) Losartan and Enalapril can also reduce cardiomyocytes apoptosis, and it wasthe important mechanism that the two drugs improve heart function and inhibit ventricular hypertrophy, and there is no significant difference between two drugs...