O'Hair D P, McManus R P, Komorowski R
Department of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee.
Ann Thorac Surg. 1994 Nov;58(5):1311-5. doi: 10.1016/0003-4975(94)91902-x.
Similar to human allografts, cardiac xenografts also appear susceptible to chronic vascular rejection. The study described here evaluated the influence of mycophenolate mofetil on the incidence and severity of vascular rejection in a primate model of heart xenotransplantation. Nine baboons received heterotopic cardiac xenografts from donor cynomolgus monkeys. All baboons were placed on a cyclosporine and methylprednisolone-based immunosuppressive regimen. In addition, group 1 baboons received azathioprine (4 mg.kg-1.day-1) and group 2 baboons received mycophenolate mofetil (70 mg.kg-1.day-1). Biopsy specimens were obtained at regular intervals and reviewed blindly by a pathologist. A total of 50 biopsy specimens, 29 from group 1 and 21 from group 2, were reviewed. Histologic evidence of vascular rejection was present in 16 of the 29 biopsy specimens from the group 1 animals and in only 2 of the 21 specimens from the group 2 animals (p < 0.005). The mean graft survival was 3 months in group 1 versus 10 months in group 2. At 1-year follow-up, profound intimal proliferation in the coronary vasculature was noted in the biopsy specimens from group 1, whereas the coronary vessels were found to be normal in the specimens from group 2. The use of mycophenolate mofetil, in combination with cyclosporine and steroids, resulted in reduced vascular rejection and prolonged xenograft survival.
与人类同种异体移植相似，心脏异种移植似乎也易发生慢性血管排斥反应。本文所述的研究评估了霉酚酸酯对心脏异种移植灵长类动物模型中血管排斥反应的发生率和严重程度的影响。9只狒狒接受了来自供体食蟹猴的异位心脏异种移植。所有狒狒均采用基于环孢素和甲泼尼龙的免疫抑制方案。此外，第1组狒狒接受硫唑嘌呤（4mg·kg-1·天-1），第2组狒狒接受霉酚酸酯（70mg·kg-1·天-1）。定期获取活检标本，并由病理学家进行盲法评估。共评估了50份活检标本，其中第1组29份，第2组21份。第1组动物的29份活检标本中有16份存在血管排斥的组织学证据，而第2组动物的21份标本中只有2份出现这种情况（p<0.005）。第1组的移植物平均存活时间为3个月，而第2组为10个月。在1年的随访中，第1组活检标本中观察到冠状动脉血管有严重的内膜增生，而第2组标本中的冠状动脉血管正常。霉酚酸酯与环孢素和类固醇联合使用可减少血管排斥反应并延长异种移植物存活时间。
