| Background:Currently ischemic heart disease has become a worldwide problem which is harmful to human health. In our country the trend of ischemic heart disease incidence and mortality were upwards year by year. Although some revascularization methods as PTCA, CABG and TMLR could be used to open infarct-related artery as early as possible. That could save hibernate or stunning myocardium. However, such methods could not save the necrosis myocardium. Necrosis myocardium was replaced by fibrous tissue. That changes caused ventricular remodling, expanding, then congestive heart failure. Today it was the problem to solve that how could we increase angiogenesis in the infarct area in order to increase blood supply and improve cardiac function. With the cell biology and gene technology development, therapeutic angiogenesis might solve the problem. Therapeutic angiogenesis was a therapy that through artificial means to raise angiogenesis factor in the lesions,prom- ote local angiogenesis and collateral circulation. Among these angiogenesis factors, human basic fibroblast growth factor (hbFGF) was expected to become a new and effective factor of myocardial infarction's treatment.Objective:hbFGF gene was injected into myocardial infarction region of pigs by coronary perfusion method. After four weeks we observe the indicators that included ultrasound result of the heart, coronary angiography, infarct region neovascularization density and the area of myocardial infarction. Through these we could know hbFGF gene therapy's effect to cardiac function and angiogenesis.Methods:1.Model establishment:All pigs were feeded in 1 week before experiment. Before operation aspirin was taken orally. Ketamine, diazepam and sumianxin as foundation anesthesia were given. Then the skin incision, separating right femoral artery, puncturing, measuring ventricular pressure and taking the coronary angiography were operated step by step. We used balloon to block vessel 120min in 1/3 distal LAD and move the ballon in a small area to make endothelial lesion. Model success criteria : ECG monitor: at least two related leads ST-segment elevating more than 0.2mV, formating of AMI ECG typical performance; after 6 hours when operation finished, cTnI and CK-MB of blood increasing twice more than normal; distal LAD occlusion from blocking area with angiography.2.bFGF gene therapy for pigs with acute myocardial infarction: After two week from model establishment ,the experimental pigs were randomly divided into 2 groups: group I.hbFGF gene therapy group (n = 6): OTW coronary balloon occluded LAD , while hbFGF gene were infused by balloon catheter. Group II. the control group (n = 4):using the same method ,but 5 ml DMEM medium was infused. After four weeks we redo the heart ultrasound and coronary angiography. Then the pigs were killed. The heart was retrieved to observe the general changes in the structure of the heart. The specimens were used for immun- ohistochemical and measuring the myocardial infarct size.Results:1.After Four weeks when the pigs were treated,we observed the hbFGF's effect to cardiac function through ultrasound and HE staining:Ultrasound results: LVEDV did not change significantly in group I(△LVEDV =0.4±0.7), while in group II LVEDV after treatment was significantly increased [(△LVEDV=10.9±2.1), p <0.01]. In group I EF after treatment was significantly increased (△EF=0.10±0.09), while in group II EF had no significant changes (△EF =-0.05±0.04). There was a statistically significant between two groups(p <0.05). In group I FS after treatment was significantly increased (△FS=0.09±0.05), while in group II FS had no significant changes (△FS = -0.01±0.05). There were statistically significants between two groups in the parts of△FS (p <0.01).Area of myocardial infarction:In group I ratio of myocardial infarction size was8.82±3.49. while In group II that was 17.46±5.39 ( P <0.01)2. Through coronary angiography and immunohistochemical method measured factor VIII endothelial cell-specific markers to observe angiogenesis in infarct zone:Coronary angiography Rentrop score: In group I after treatment Rentrop scores were increased significantly (Rentrop =2.32±0.56 ),while in group II Rentrop scores did not change significantly (Rentrop =1.00±0.27). There were statistically significants between two groups.( P <0.01).Immunohistochemical method measureing factor VIII endothelial cell-specific markers: In group I, angiogenesis were observed significantly in myocardial infarction zone (22.4±2.3 / HPF), while in group II ,there were no significant increase(3.9±1.2 / HPF). P <0.01(between two groups).Conclusion:1. It was a repeatability and practical method to establish small pig model of acute myocardial infarction by coronary Intervention which had a higher rate of success.2. HbFGF gene therapy for acute myocardial infarction could promote angiogenesis, decrease the infarct area and improve heart function.
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