Irreversible chronic vascular rejection occurs only after development of advanced allograft vasculopathy: a comparative study of a rat cardiac allograft model using a retransplantation protocol.

Indefinitely surviving WF.1L (RT1(1)) cardiac allografts transplanted to LEW (RT1(1)) recipients provide an ideal model for controlled comparative studies of chronic vascular rejection (CVR). To determine the stage of development at which the progressive CVR can be reversed when deprived of an ongoing recipient alloimmune response, WF.1L-LEW cardiac allografts were retransplanted back into syngeneic donor strain WF.1L recipients at specific time periods after initial allogeneic engraftment and were maintained in WF.1L syngeneic hosts for a further 40 days. The vascular changes in the retransplanted allografts were compared with those of nonretransplanted allografts and with nonretransplanted and retransplanted LEW-LEW isografts examined at similar time periods. The early vasculopathic inflammatory changes were consistently reversed by retransplantation of the cardiac allografts back into syngeneic recipients after 20 days and 40 days of allotransplantation. Syngeneic retransplantation of the cardiac allografts at 60 days after allotransplantation did not reverse the essentially nonvasculitic occlusive vasculopathy invariably present in WF.1L-LEW cardiac allografts at this time period. Thus, the vasculitic and minimal subocclusive myointimal changes associated with early CVR in this model are alloantigen dependent and reversible. Irreversible CVR occurs only after advanced proliferative vasculopathy has been established in the allogeneic host.