The Effect Of Pentoxifylline And Immunodepressant On Xenograft Survival In Mouse-to-Rat Cardiac Xenotransplantation And Its Mechanism Study

Objective: To establish a model of mouse-to-rat cardiac heterotopic xenotransplantation in neck. Methods: NIH mice and Wistar rats were served as donors and recipients respectively. The aorta of the donor heart was anastomosed end-to-end to the right common carotid artery of the recipient and the pulmonary artery was anostomosed end-to-end to the right external jugular vein by cuff technique.Xenograft function was assessed by daily palpation;the day of rejection was defined as the day when no pulsations could be detected in the transplanted heart. The rejected xenografts were analysed by histological way. Results: 20 times of transplantation were done with the successful rate of 80%. The mean survival time of the xenografts was 49.3±16.2hr. The histology of the rejected xenografts showed widespread intravascular thrombosis,hemorrhage and associated with a large of infiltrated inflammatory cells,focal ischemic infacts and coagulative necrosis. Conclusion: The model of mouse-to-rat cardiac xenotransplantation,which is established in heterotopic neck by cuff technique, is a simple, reliable and easily operated model,and its observation is easy also. This model is good and suitable for studying xenotransplantation. Objective: To explore the mechanism of DXR by dynamic observation of histologic and immunohistologic changes in Mouse-to-Rat Cardiac Xenografts. Methods: A model of mouse-to-rat cardiac heterotopic xenotransplantation in neck was established by cuff technique. Untransplanted mouse hearts were studied as controls(n=4). Other xenograft recipients were killed and cardiac xenografts harvested at 3(n=4), 8(n=4), 16(n=4), 24hr(n=4) after transplantation while the hearts were still beating.For determination of survival time,the other group cardiac hearts(n=16) were not harvested until rejection time.All samples were examined by HE and immunohistochemistry. Antibodies include C3, IgM, IgG, E-selectin and macrophage marker-CD68. Results: The mean survival time of the xenografts was 49.3±16.2hr. During the period of post-transplantation, the degree of rejection in xenografts became more and more serious till they were ultimately rejected. Immunohistochemical examination show: ① C3 were not detected in the xenografts at any time during the course of rejection; ②Obvious deposition of IgM was found in the grafts from 3hr after transplantation, and from this time ,IgG deposition get more and more abundant also;③There was marker of EC activation as early as 3hr posttransplantation(increased expression of E-selectin); ④ There was progressive infiltration of the grafts by macrophages. Conclusion: Mouse-to-rat cardiac xenotransplantation can served as a DXR reaseach animal model. EC activation, IgM and IgG, macrophage infiltration involved in DXR except C3.Objective: To evaluate the significance of tissue factor in delayed xenograft rejection. Methods: A model of mouse-to-rat cardiac heterotopic xenotransplantation in neck was established by cuff technique.Untransplanted mouse hearts were studied as controls.Other xenograft recipients were killed and cardiac xenografts harvested at 3, 8, 16, 24hr after transplantation while the hearts were still beating.For determination of survival time,the other group cardiac hearts were not harvested until rejection time.All samples were examined by HE , immunohistochemistry and RT-PCR. Antibodies include tissue factor, fibrinogen and leukocyte marker-CD45. Expression of tissue factor mRNA was examinied by RT-PCR. Results: During the period of post-transplantation, the degree of blood coagulation and rejection in xenografts became more and more serious till they were ultimately rejected. There was progressive infiltration by CD45 positive cells and fibrinogen deposition in grafts from 3hr after transplantation. Notable expression of tissue factor and its mRNA on donormyocytes and endothelial cells was detected at 3hr after transplantation. And from this time, their expression decreased gradually and was not detected nearly at post-transplanted 16hr. In contrast, t...