Anticoagulation Therapy In Delayed Xenograft Rejection

Objective Xenotransplantation is a possible solution to the great shortage of transplantation donor organs. After heart xenotransplantation hyperacute rejection occurs. Delayed xenograft rejection (DXR)is a syndrome in xenograft recipients in which hyperacute rejection has been avoided or suppressed. It is characterized by endothelial activation, monocyte and NK cell infiltration, cytokin expression upregulation, platelet aggregation and thrombosis. Transgene pig organ avoid the hyperacute rejection successfully, however, several days later, DXR occurs. Previous studies showed that immune activation and coagulation activation are two closely related factors. Immune quiescent cannot be achieved unless profound immune suppression. Anticoagulation therapy has become an important method to prolong xenograft survival time. This study use anticoagulation drug combinations, such as Aspirin plus low-molecular-weight heparin and ligustrazine plus Salvia-miltiorrhiza Bge to counteract the rejection, aiming to find an effective therapy to prolong the xenograft survival time. Methods Ion exchange and gel infiltration chromatography are used to purify the cobra venom factor from Chinese cobra venom powder. In guinea pig to rat heart xenotransplantation model, cobra venom factor is administrated to avoid hyperacute rejection, and thus delayed xenograft rejection model is made. Different groups are set by method of management. Xenograft rejection is evaluated.Results Average survival time in different groups: Hyperacute rejection group (HAR) 17±7 minutes, delayed xenograft rejection group (DXR) 41 ±3 hours, low molecular weight heparin plus aspirin group (HA)43±3 hours, tetrandrine group (TET) 42+3 hours, dexamethasone group(DEX) 53±2 hours, Ligustrazine plus Salvia-miltiorrhiza Bge group(LS) 61 ±4 hours, ligustrazine plus Salviamitiorrhiza Bge and dexamethasone group(DLS) 61+2 hours. Statistical analysis shows that HA and TET groups have no obvious differencecompared with DXR(p>0.05), DEX, LS,DLS groups have great difference with DXR (p<0.01) . DLS has no difference compared with LS (p>0.05). Conclusion In delayed xenograft rejection, large dose of low molecular weight heparin and aspirin or tetrandrine did not effectively prolong graft survival time (GST). Dexamethasone or ligustrazine plus Salvia-miltiorrhiza Bge prolonged GST, but their combination failed to further prolong GST.