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An Experimental Study On Heterotopic Heart Transplantation In Rat

Posted on:2003-10-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z ZhaoFull Text:PDF
GTID:1104360062485472Subject:Cardiovascular surgery
Abstract/Summary:PDF Full Text Request
Heart transplantation is the most effective method for treatment of severe end-stage heart diseases. With the development of modern medicine, immunosuppressive drugs and operative technology, more and more patients with end-stage heart failure or very complicated congenital heart diseases want to receive heart transplantation in order to improve their own quality of life. However, up to now, there are still many problems such as ischemia reperfusion injury, acute or chronic graft rejection, cardiac allograft vasculopathy, heart preservation and myocardial protection etc. in this field need to be further investigated.In the present study, we established the model of heterotopic heart transplantation in Sprague-Dawley ( SD) rats to study the following issues: 1) myocardial cell apoptosis after heterotopic heart transplantation; 2) ischemia/reperfusion injury after the transplantation; 3) the relationship among the results after allografting, cell apoptosis and ischemia/reperfusion injury;(4) possible antioxidative effects of P - ecdysterone(EDS)and L-arginine(L-Arg) on myocardial injury induced by heart transplantation in rats.Methods:The model of heterotopic heart transplantation established in SD rats with an age of 12 weeks. The procedure was performed according to standard Ono and Lindsey's original model with slight modification. That is to say, the donors' right or left pulmonary artery was anatomized with the recipients' inferior vena cava. After allografting, the morphological changes of hearts and other organs were examined by histopathological method and electron microscopy. On the 1st, 3rd, 7th, 10th day after the heart transplantation, observation was conducted on the activity of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), creating phosphokinase (CPK) & the content of malondialdehyde (MDA) in plasma, and MDA in myocardium. Superoxide dismutase (SOD) in serum was determined by radioimmunoassay. Cell apoptosis in the donor hearts was identified by TUNEL method. Protein products of Bcl-2,Bax was assessed by immunohistochemistry. And then, the serum contents of GOT ,CPK and LDH, ET, NO were measured in heterotopically transplanted. rat hearts that were given EDS and L-Arg. Targets of hemodynamics and contractility of recipient's myocardium were measured. Results:1. The model of heterotopic heart transplantation was successfully established. We found that this model was simple and stable. The ratio of success was 80-90%.2. In donor myocardium, swelling, necrosis, hypertrophy and breaking myocardial fibers were seen by routine light microscopy. There was an increase and hypertrophy of interstitial cells and most of which were8lymphocytes. Other organs had significant changes.Mitochondria of myocardium were markedly swollen, with dissolution of cristae in donor hearts. In some mitochondria, the matrix space was dilated and vacuolated mitochondria formed.3. After the transplantation, the serum levels of LDF, GOT and CPK were increased at different time phases. The increase appeared on the first day and reached the peak on the 7th day after the transplantation. Then the levels began to decrease but did not return to normal even on the 1 0th day after the transplantation. The serum content of MDA began to increase on the 1st day after the transplantation and continued to rise with time prolongation. However, the serum content of SOD decreased and reached its lowest level on the 7th day after the transplantation. Then it began to increase.4. Myocardial histological changes were seen on the 1st day after the transplantation and the histological grading of the myocardial injury increased with time prolongation. The apoptosis index (AI) of myocardial cells was positively correlated to myocardial histological grading. The AI reached its peak on the 7th day and then began to gradually decrease after the transplantation. He expression of Bcl-2 and Bax was observed at different time phases after the transplantation. The incre...
Keywords/Search Tags:Heterotopic, Heart transplantation, Myocardial protection, Ischemia/reperfusion injury, Rat
PDF Full Text Request
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