Retransplantation reverses mononuclear infiltration but not myointimal proliferation in a rat model of chronic cardiac allograft rejection

Episodes of acute rejection seem to play an important role in the development of chronic allograft failure, Whereas acute rejection appears to be fully reversible, at least at early stages, reversibility of chronic graft alterations is still unclear. Male Fisher F344 rat hearts were heterotopically transplanted into Lewis recipients (n=8/group). Minimal immunosuppression (rapamycin 0.5 mg/kg for 14 days) guaranteed allograft survival during the observation period (group 1). Allografted hearts were retransplanted into syngeneic recipients after 3.4 days (group 2) and 50 days (group 3) and compared with F344 isografts undergoing retransplantation after 4 days (group 4) and with F344 isografts without a second procedure (group 5), All organs were removed after 100 days and morphologically and immunohistologically assessed. Allografts of group 1 developed concentric myointimal proliferation with dense intramural and perivascular mononuclear infiltration and intravascular thrombosis in 59+/-7% of coronary arteries, Retransplantation into syngeneic recipients almost completely abolished mononuclear infiltration, but did not affect the development of myointimal proliferation (groups 2/3: 46+/-7%/31+/-24%, NS). Isograft retransplantation resulted in a similar incidence of coronary lesions (group 4: 37+/-9%, NS), whereas coronary arteries of isografts without a second transplant procedure (group 5) remained normal (0%, P<0.001). In conclusion, syngeneic retransplantation of allografts reverses mononuclear infiltration but not myointimal proliferation. The development of coronary lesions in retransplanted isografts underlines the participation of antigen-independent stimuli in the development of myointimal proliferation. These experiments further support the hypothesis of an interaction of antigen-dependent and antigen-independent factors for the development of coronary myointimal proliferation.