Suckfüll M M, Pieske O, Müdsam M, Babic R, Hammer C
Institute for Surgical Research, Ludwigs-Maximilians University, Munich, Germany.
Transplantation. 1994 Jan;57(2):262-7. doi: 10.1097/00007890-199401001-00019.
The mechanisms leading to the hyperacute rejection of a vascularized xenograft are still incompletely understood. The first stage of the rejection process is when blood of the recipient comes into contact with the endothelium of the xenograft. A working heart model was used to examine endothelium-related processes and their impact on organ function. Pig hearts were perfused with porcine (autologous) or human (xenogeneic) blood. Cardiac function was evaluated by calculating the stroke work index, arteriovenous oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial activation, its antagonist TXB2, and myoglobin reflecting myocardial damage were measured in the hemoperfusate. H&E and PAS staining and immunohistological demonstration of factor VIII-related antigen was performed. Xenogeneic perfused porcine hearts showed significantly less stroke work, a higher arteriovenous oxygen difference, and an increased coronary resistance. Factor VIII-related antigen could not be demonstrated immunohistologically on the endothelium after xenogeneic perfusion. PgF1a levels were significantly higher in the xenogeneic hemoperfusate, indicating endothelial cell activation. The concentration of myoglobin in the hemoperfusate remained within normal values and was similar during autologous and xenogeneic perfusion. Therefore endothelium-related processes are likely to affect the coronary circulation--thus being one mechanism leading to diminished cardiac performance during hyperacute rejection.
导致血管化异种移植物超急性排斥反应的机制仍未完全明了。排斥反应过程的第一阶段是受者血液与异种移植物的内皮接触。采用工作心脏模型来研究与内皮相关的过程及其对器官功能的影响。用猪(自体)或人(异种)血液灌注猪心脏。通过计算每搏功指数、动静脉血氧含量、冠状动脉血流量和阻力来评估心脏功能。在血液灌流液中检测作为内皮激活标志物的前列环素F1a、其拮抗剂血栓素B2以及反映心肌损伤的肌红蛋白。进行苏木精-伊红染色、过碘酸-雪夫染色以及因子Ⅷ相关抗原的免疫组织学检测。异种灌注的猪心脏每搏功显著降低,动静脉血氧差增大,冠状动脉阻力增加。异种灌注后,在血管内皮上无法通过免疫组织学检测到因子Ⅷ相关抗原。异种血液灌流液中前列环素F1a水平显著升高,表明内皮细胞被激活。血液灌流液中肌红蛋白浓度保持在正常范围内,自体灌注和异种灌注时相似。因此,与内皮相关的过程可能会影响冠状动脉循环,从而成为超急性排斥反应期间心脏功能降低的一种机制。