EVIDENCE THAT GRAFT CORONARY ARTERIOSCLEROSIS BEGINS IN THE EARLY PHASE AFTER TRANSPLANTATION AND PROGRESSES WITHOUT CHRONIC IMMUNOREACTION- HISTOPATHOLOGICAL ANALYSIS USING A RETRANSPLANTATION MODEL

The histopathological features of chronic rejection and its initiation were assessed using rat heterotopic heart transplantation and retrans plantation models. Fully allogeneic or minor, non-MHC antigen-mismatch heart grafts transplanted into recipient rats treated with a short co urse of FK506 showed long-term survival but developed graft atheroscle rosis after 40 days posttransplantation. Retransplantation of allograf ts back into the original donor strain did not prevent graft atheroscl erosis if the grafts had resided in the primary recipient for up to 5 days; residence in the primary allogeneic recipient for less than 4 da ys did not result in graft atherosclerosis in the secondary recipient. Short-course administration of FK506 did not affect the production of these changes. Graft coronary arteriosclerosis begins between 3 and 5 days posttransplantation and progresses without continuous allogeneic immunological drive. The present findings will provide a new means by which to approach the analysis of development of chronic allograft re jection.