Objective     To explore the mechanism of delayed xenograft rejection (DXR) by dynamic observation of histological 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. NIH mouse hearts not transplanted served as controls (n=4). Some xenograft recipients were killed and cardiac xenografts harvested at end of 3

8

16

24

h (n=4 for each time point) after transplantation. The cardiac hearts (n=16) of some xenograft recipients were not harvested until rejection time to determine their survival time. All heart samples were examined by HE and immunohistochemistry for semi-quantitative determination of antibodies including C

3

IgM

IgG

E-selectin and macrophage marker--CD68.      Results     During the period after transplantation

the degree of rejection of xenografts became more and more serious till ultimate rejection. The mean survival time of the xenografts was (49.3±16.2) h. Immunohistochemical examination showed C

3

were not detected in the xenografts at any time during the course of rejection; From 3 h after transplantation

obvious deposition of IgM was found in the grafts and IgG deposition got abundant; E-selectin expression was found as early as 3 h after transplantation and increased gradually; There was progressive infiltration by macrophages in the grafts.      Conclusion     Mouse-to-rat cardiac xenotransplantation can serve as an animal model of DXR. Endothelial cells activation

IgM and IgG

macrophage infiltration involve in DXR development except C

3

.