Research On Cardiomyocyte Apoptosis In Acute And Chronic Myocardial Ischemia

Background: It was believed that cardiac ischemia and ischeniia-caused cardiomyocyte necrosis is a all or none?relationship. However, recent reports have demonstrated that the impacts of ischemia to myocardium are in many ways: when the ischemic period is shorter than 5mm, myocardial injury is reversible, the ischemia myocardium will return to normal rapidly after reperfusion; brie.f periods of acute myocardial ischemia protect against ischemia reperfusion injury, this phenomenon is called ischemia preconditioning (IPC); 5mm to 20 mm myocardial ischemia can cause a fully reversible yet prolonged mechanical dysfunction despite restoration of normal coronary flow, this is called myocardial stunning (MS); chronic reduced coronary blood flow can cause persistently impaired myocardial and LV function at rest , but the impaired heart function could be partially or completely restored to normal by improving blood flow or reducing oxygen demand, this is hibernating myocardium (I-fM); prolonged periods of myocardial ischemia (longer than 30 mm ) can cause tissue injury and cell death. For a long time it is believed that necrosis is the only way to death caused by myocardia ischemia and reperfion. Recently, considerable attention has been directed to another form of cell death , referred to as apoptosis. Recent reports have demonstrated that apoptosis does occur in cardiomyocyte by agents that have traditionally been thought to produce necrosis such as ischemia and hypoxia. The reseach relating to the developing rule and regulatory mechanism of cardiomyocyte apoptosis caused by ischeniia are on the early stage. It is lack systemic research on the expression of apoptotic ralated protein after acute myocardial infarction, hibernating rnyocardium, ischemia-reperfusion injury and ischemia preconditioning. Angiotensin II can induce cardiomycyte apoptosis, and .Angiotensin II type 1 antagonist Losartan can pretect against ischemic reperfusion injury, but whether the protect effect of Losartan to is relatd to cardiomyocyte apoptosis is unclear. Objectives: On the basis of replicated AIvfl,HM, MS. IPC and ischemic reperfusion(IR) model, we investigating cardiomyocyte apoptosis and the expression of Bcl-2,Bax and FAS in acute and chronic myocardium ischemic, the effect of IPC and Losartan to cardiiomyocyte apoptosis of ischemic reperfusion are also observed. Materials and methods: I .The rat in vivo myocardial stunning model was made by ligating the LAD 1 5mm followed by 2h and 6h reperfusion. Inspecting cardiomyocyte apoptosis and BcI-2,Bax and FAS protein expression in MS. 2.The IPC model of rat was made with the protocol consisting of 3 cycles of 5mm of myocardial ischemia and 5mm of reperfusion. Inspecting the effect of IPC to ischemia reperfusion with 40mm ischemia and 6h reperfusion. Collecting blood sample for biochemistry measurement, measuring the infarct area, Inspecting cardiomyocyte apoptosis and Bcl-2,Bax and FAS protein. 3.Making AMI model with the method of ligating the left anterior descending coronary artery of rat. Investigating cadiomyocyte apoptosis and Bcl- 2,Bax and FAS proteins in the group of 2h,4h, 6h, 24h, 48h and 7d after AMI. 4.To establishing HM animal model, implanting the proximal LAD of juvenile pigs with a 5mm-long and 2.0mm fixed internal diameter Delran occluder, then housing the animals for 21 weeks. Confirming the MM with selective left coronary angiography, low dose dobutamine echocar...