Effects of Antiplatelet Agents on the Graft Survival in Murine Cardiac and Skin Transplantation Model

Abstract

Methods: In the minor major histocompatibility (MHC) mismatch model, BALB/c (H2d) mice underwent heart transplantation from B10.D2 (H2d) mice. In the major MHC mismatch model, CBA (H2k) mice were used as the recipients and C57BL/10 (H2b) mice as donors. The recipients were divided into four groups and each group was treated with distilled water (DW), sarpogre- late, cilostazol, or clopidogrel respectively. For skin transplantation, the recipients in the minor MHC mismatch model were divided into four groups similar to those in cardiac transplantation. The recipients in the major MHC mismatch model were divided into DW-treated and sarpogrelate-treated groups. All treatments were done by the per oral route of administration. Results: For graft survival in the minor MHC mismatch model of cardiac transplantation, sarpogrelate-treated group showed increased median survival time (MST) compared to the other groups (DW-treated group 17.5 days, sarpogrelate-treated group 88 days, cilostazol-treated group 13 days, clopidogrel-treated group 23 days). Similar results were observed in the major MHC mismatch model. In the major MHC mismatch model, the expression of adhesion molecules (L-selectin, intercellular adhe- sion molecule-1 (ICAM-1), Mac-1, lymphocyte function associated antigen-1 (LFA-1)) was significantly higher in DW-treated group compared to sarpogrelate-treated group (P<0.05) In the minor MHC mismatch model, MST in the antiplatelet-treated skin graft group was not remarkably prolonged compared to DW-treated group. In the major MHC mismatch model, sarpogre- late-treated group showed prolonged survival compared to DW-treated group (MST 25 vs. 19 days, P<0.05). There was no statistically significant difference in the proportion of activ ated T cells and regulatory T cells. Conclusions: The tendency for a better survival of grafts was observed in the sarpogrelate- treated skin and heart transplant group compared to DW-treated group. However, further mechanistic study is necessary to these results.