The Expression Of Adhesion Molecules And The Effect Of LFA-lmAb With AS-ICAM-1 ODN On Cardiac Xenograft Rejection

Heart transplantation has been considered as the only effective therapy for end-stage heart disease at the present time. But the use of transplants has a big obstacle, that is the shortage of human donors. Transplantation of tissues between different species (i. e., xenotransplantation) has enormous practical potential. Xenogeneic donors are envisioned as a potentially infinite supply of optimal quality organs. A lot of studies had been performed, xenotransplantation has been thwarted by immunologic obstacles all the same. In this experimental study, the model of rat to rabbit heterotopic cardiac xenotransplantation was established to research the discordant cardiac xenotransplantation. Immunoadsorption by perfusion of blood through rat kidney and Chinese Cobra venom were used to delay the hyperacute rejection. At the same time, the expression of adhesion molecules in cardiac xenograft was observed. The monoclonal antibody (mAb) against recipient lymphocyte function associated antigen-1 (LFA-1) with antisense oligodeoxynucleotides (AS-ODN) of donor intercellular adhesion molecule-1 (ICAM-1) were used to prolong the cardiac xenograft survival. It could provide new special immunosuppression therapy by combination using species-specific mAb with AS-ODN for xenotransplantation. Thisstudy consists of the following three parts.Part one: An animal model of rat to rabbit heterotopic discordant cardiac xenotransplantationObjective To study the discordant cardiac xenotransplantation, an animal model of rat to rabbit heterotopic cardiac xenotransplantation was established. Methods In this experiment, Sprague-Dawley rats served as donors and New Zealand white rabbits as the recipients. The aorta and the main pulmonary artery of the donor were anastomosed with the right common carotid artery and the external jugular vein of the recipient respectively with the cuff technique. Results 84 times of formal transplantation were done with the successful rate being 100%. The mean time of operation was 45 minutes, 15-20 minutes for donor cervix operation and only 2-4 minutes for anastomosis were among the rest. Conclusion In this model, the localization in the model of celiac cardiac xenotransplantation is overcome and the transplanting technique is simplified.Part two: Effect of Immunoadsorption and Chinese Cobra venom on delaying rat to rabbit cardiac xenograft hyperacute rejectionObjective To study the effect of immunoadsorption by perfusion of blood through rat kidney and Chinese Cobra venom on delaying rat to rabbit cardiac xenograft hyperacute rejection and observe the expression of adhesion molecules in cardiac xenograft. Methods The animal model of rat to rabbit heterotopic cardiac xenotransplantation was developed. All animals were randomly divided into groups A, B and C receiving the following therapies respectively: untreatment in group A, immunoadsorption in group B and Chinese Cobra venom in group C. Thesurvival time of cardiac grafts was noted. The content of the recipients plasmatic immunoglobulin G,M and complement 63 was detected. The pathologic examination of the rejected hearts was observed using hematoxylin and eosin staining. The deposition of rabbit immunoglobulin G, M and complement €3 on rejected rat cardiac grafts was assessed with the use of immunofluorescence staining. The expression of P-selectin and E-selectin was examinated using immunohistochemical method. Results The grafts survival time in groups A, B and C were gradually prolonged, the different among three groups was significant (P<0. 01). The content of the recipients plasmatic immunoglobulin G, M and complement €3 were decreased in different degrees because of the different therapies. Pathological study showed hyperacute rejection in the grafts in group A, and acute vascular rejection in the grafts in groups B and C. The deposition of rabbit immunoglobulin G, M and complement C3 on all rejected rat cardiac grafts differed in degree. P-selectin expression was observed only in group A, E-selectin expressio...