参附注射液对心脏空跳保存心肌保护作用的实验研究

Despite major a chievements in heart transplantation, we still face the persistent problem of a shortage of donor hearts. Current protocols for preserving donor hearts utilize hypothermic arrest and simple storage by a variety of crystalloid-based cardioplegic and preservation solutions. This is a suboptimal approach owing to the inevitable associated ischemia. Ischemic damage contributes to the risk of post-transplantation primary graft dysfunction and limits organ procurement and safe storage time. It has been suggested that donor heart preservation under beating state provides better myocardial protection. Beating preservation, at least in theory, thereby overcomes the three major weaknesses in traditional static cold storage by ⑴ avoiding ischemia/reperfusion injury, ⑵ avoiding cold injury, and ⑶allowing viability assessment. However, a perfusion device (mini-cardiopulmonary bypass) is necessary when preserves the donor heart in a beating state ex vivo and prolonged cardiopulmonary bypass is associated with problems of inflammatory reaction, disorder of microcirculation, blood cell damage and maintain hearts in a good beating state. Disorder in hemodynamic and oxygen metabolism is occurs during preservation donor heart in a beating state, which is considered similar to gas collapse or blood collapse in early stage of shock by Chinese medicine. So we assume that adding a dose of Chinese medicinal, Shen-Fu injection with a function of replenishing qi to stop collapse, to perfusion solution should be benefit to the myocardial protection. Shen-fu Injection for the treatment of syncope has a function of restoring yang to save from collapse. Modern medicine has proved Shen-fu injection can relieve the inflammatory reaction, improve microcirculation, protection red blood cells and positive inotropic effect. Shen-Fu injection has been clinically used for treatment of many kinds of diseases, especially being famous for its traditional cardiovascular protective effectiveness, such as shock, stretching coronary artery, stabilizing blood pressure, and improving heart function. Therefore, we assume that adding Shen-fu injection into the perfusate for preservation donor heart in a beating state may ameliorate the harmful effects of cardiopulmonary bypass and provide a better myocardial protection. The purpose of our study is to test the hypothesis that Shen-Fu injection could attenuate inflammatory reaction, relieve disorder of microcirculation, reduce blood cell damage and maintain hearts in a good beating state in porcine hearts.

心脏移植是心脏终末期疾病的主要治疗手段。然而，现有的供心保存方式无法保证有效的使用每一颗存在的供心，使供心短缺更加严重。只有改善供心的保存技术，才能在一定程度上缓解供心短缺。实验证明心脏不停跳保存优于心脏单纯低温保存、能扩大供心标准、延长心脏保存时间、便于移植前组织配型和供心的功能评估。尽管如此，但心脏不停跳保存又面临着炎症反应、微循环障碍、血细胞破坏和维持心脏良好跳动的问题，效果仍然不十分理想。由于体外循环心脏不停跳保存过程中发生了循环动力和氧代谢异常，与休克早期的气脱或血脱十分相似。因此设想在心脏不停跳保存的灌注液中加入有益气固脱作用的参附注射液应当有利于心肌保护。参附注射液用于治疗厥脱，具有益气温阳，回阳救逆，益气固脱和温通心脉的作用。现代医学证明参附注射液能减轻炎症反应、改善微循环、保护红细胞和正性肌力作用。所以,本实验拟把参附注射液加入心脏不停跳保存的灌注液中，使心肌保护最大化。

心脏移植是心脏终末期疾病的主要治疗手段。然而，现有的供心单纯低温保存方式由于缺血的存在，而无法保证有效的使用每一颗存在的供心，使供心短缺更加严重。实验证明心脏不停跳保存由于减轻了缺血-再关注损伤和组织水肿从而优于心脏单纯低温保存、能扩大供心标准、延长心脏保存时间、便于移植前组织配型和供心的功能评估。但是,不停跳心脏保存,需要类似于体外循环机装置的连续灌注。体外循环则引起血液红细胞破坏、炎症反应等，从而会影响心肌保护效果。本课题主要研究参附注射液对红细胞是否有保护作用，对空跳供心保存的心肌能量代谢的影响，对心肌β肾上腺素受体活性的影响以及对不停跳供心保存的心肌保护作用。实验结果显示:在体外循环灌注压力保持在40～60mmHg时，参附注射液组需要的血液灌注流量明显的小于对照组，说明参附注射液可以改善微循环;在体外循环中，参附注射液组的游离血红蛋白浓度低于对照组，表明参附注射液对红细胞有一定的保护作用。参附组BCL-2表达高于非参附组。说明参附注射液有抗凋亡作用。心肌病理结果及电镜结构检查结果显示参附注射液对体外循环供心心肌有保护作用。