【作者】 薛辉；

【导师】 吴清玉；

【作者基本信息】 清华大学 ， 临床医学， 2010， 博士

【摘要】 心脏保护液目前已应用于心脏外科各种体外循环下心脏直视手术和心脏移植手术中,能够为心脏提供有效的心肌保护,极大地促进了心脏外科的发展。根据目前国内外在心脏手术中对心脏保护液的选择及对心脏保护液的研究进展,我们研制了新型的心脏保护液,并通过离体鼠心Langendorff模型及小型猪体外循环心脏直视手术模型将它和目前广泛应用于心脏手术中的HTK心脏保护液及St·ThomasⅡ心脏保护液进行了对比研究,旨在进一步研究心脏保护液的作用机制及最佳成份以提高心肌保护效果。本研究分为两部分,第一部分为通过建立离体鼠心Langendorff模型进行离体鼠心灌注-冷存-再灌注实验,模拟心脏移植手术对心脏供体获取、保存及移植过程中心脏保护液对心肌的保护。实验从血流动力学(冠脉流量、心率、左心室收缩峰压、左心室舒张期末压、左心室发展压,心脏作功指数、左心室收缩期压力最大上升速率、左心室舒张期压力最大下降速率)、心肌酶(肌酸激酶同工酶及心肌肌钙蛋白T)、心肌含水率、冠状动脉内皮细胞功能(一氧化氮含量、内皮素-1含量)、抗过氧化反应(超氧化物歧化酶、丙二醛)、心肌三磷酸腺苷和心肌病理结构(光镜、电镜)等方面对新型心脏保护液、HTK保护液和ST·ThomasⅡ保护液的心脏保存效果进行评价。结果显示,新型心脏保护液在各方面均优于或等同于HTK保护液和ST·ThomasⅡ保护液的心脏保存效果。第二部分为通过建立小型猪体外循环手术模型进行小型猪体外循环下心脏直视手术实验,模拟临床体外循环下心脏直视手术过程中心脏保护液对心肌的保护。实验从血流动力学、心肌酶、心肌含水率、冠状动脉内皮细胞功能、抗过氧化反应和凋亡心肌细胞检测(凋亡细胞形态学观察、凋亡细胞阳性率、心肌细胞凋亡相关基因蛋白表达)等方面对新型心脏保护液、HTK保护液和ST·ThomasⅡ保护液的心脏保护效果进行评价。结果显示,新型心脏保护液在各方面均优于或等同于HTK保护液和ST·ThomasⅡ保护液的心肌保护效果。两部分实验分别建立了用于心脏保护液研究的离体及在体动物实验模型,初步检验了新型心脏保护液对大鼠及小型猪的心肌保护作用并得到了较为满意的实验结果,为下一步对心脏保护液的实验研究打下基础。更多还原

【Abstract】 Cardioplegia solution is now used in a variety of open heart surgery under cardiopulmonary bypass and heart transplant surgery; the solution can provide effective myocardial protection, which greatly promoted the development of cardiac surgery. Based on the current seletion of cardioplegia solution during the operation and the research of myocardial protection at home and abroad, we have developed a new cardiaoplegia solution and make a comparative reseach with the HTK solution and St·ThomasⅡsolution which is widely used in cardiac surgery through the isolated rat heart Langendorff model and mini-pig open heart surgery under cardiopulmonary bypass model. The reseach is designed to further study the mechanism and the best ingredients of cardilplegia solution to enhance the myocardial protective effect.The research is divided into two parts; the first part is to conduct the isolated rat heart perfusion - cold storage - reperfusion experiment through the establishment of isolated rat heart Langendorff model to simulate the myocardial protection of the cardioplegia solution during the heart transplant surgery on the heart donor acquisition, preservation and transplantation processes. The experiment evaluate the effect of heart preservation of new cardioplegia solution, HTK solution and ST·ThomasⅡsolution from the hemodynamics (coronary flow, heart rate, left ventricular peak systolic pressure, left ventricular end-diastolic pressure, left ventricular developed pressure, cardiac work index, maximal rate of left ventricular systolic pressure, maximal rate of left ventricular diastolic pressure), myocardial enzymes (creatine kinase MB and cardiac troponin T), myocardial water content, coronary endothelial function (nitric oxide, endothelin-1), antiperoxidation (superoxide dismutase, malondialdehyde), myocardial adenosine triphosphate and myocardial pathological structure (light microscopy, electron microscopy). The results showed that the myocardial preservation effect of new cardioplegia solution was superior to or equivalent to HTK solution and ST·ThomasⅡsolution in all respects. The second part is to conduct the mini-pig open heart operation experiment through the establishment of mini-pig open heart surgery under cardiopulmonary bypass model to simulate the myocardial protection of the cardioplegia solution during the open heart surgery under cardiopulmonary bypass. The experiment evaluate the effect of myocardial protection of new cardioplegia solution, HTK solution and ST·ThomasⅡsolution from the hemodynamics, myocardial enzymes, myocardial water content, coronary endothelial function, antiperoxidation, and apoptosis in cardiomyocytes (apoptotic cell morphology, apoptotic cell positive rate and protein expression of apoptosis-related gene). The results showed that the myocardial protective effect of new cardioplegia solution was superior to or equivalent to HTK solution and ST·ThomasⅡsolution in all respects.Two experiments set up the in-vitro and in-vivo animal models to research the cardioplegia solution, tested the myocardial protective effect of isolated rat heart and mini-pig and got satisfied results. It will make a basis for followed research of cardioplegia solution.更多还原