The effect of anticomplementary cobra venom factor on hyperacute rat cardiac allograft rejection.

Cobra venom factor was used as a probe to evaluate the effect of depression of recipient hemolytic C3 activity on the sequential morphologic features of hyperacute cardiac allograft rejection in the rat. A series of ACI cardiac allografts transplanted to Lewis recipients presensitized &with ACI skin grafts was studied at arbitrary time periods over the initial 24 hours posttransplantation. The usual morphologic features of hyperacute rejection in this model, platelet aggregation, intravascular fibrin, endothelial destruction, neutrophil infiltration, and myocardial necrosis, were not observed in all allografts when recipient hemolytic C3 activity was virtually undetectable at the time of transplantation. Furthermore, allograft binding of rat C3 was not detected by immunofluorescence, although staining for IgG was commonly encountered. Despite profound depression of recipient hemolytic C3 activity, however, mononuclear cells were observed within the allograft microcirculation by 2 hours posttransplantation, and changes consistent with early cellular rejection were present in allografts examined at 24 hours. This study provides evidence that complement activation by graft-bound alloantibody is a critical effector mechanism of hyperacute rejection in this inbred rat model.