SUPPRESSION OF ACUTE REJECTION PREVENTS GRAFT ARTERIOSCLEROSIS AFTER ALLOGENEIC AORTA TRANSPLANTATION IN THE RAT

Rat aortic allografts develop arteriosclerotic alterations in the vasc ular wall that are histologically similar to those observed in chronic rejecting vascular allografts. We used cyclosporine and rapamycin (RA PA) in two different rat strain aorta transplantation models to invest igate the effect of immunosuppression on posttransplant graft arterios clerosis. High dose CsA (25 mg/kg, 3 times/week) treatment significant ly inhibited intimal proliferation in the ''strong'' WAG-BN model (P<0 .01) as well as in the ''weak'' BN-WAG combination (P<0.001), compared with untreated allogeneic controls. In the latter combination, even f ewer intimal lesions were present than in WAG autotransplants, suggest ing that CsA may also inhibit the arteriosclerotic response to mechani cal injury. RAPA (3 mg/kg, 3 times/week) was as effective as CsA in re ducing intimal lesions (P<0.01 and P<0.001 in the BN-WAG and WAG-BN mo dels, respectively). Low dose CsA (5 mg/kg, 3 times/week) was only par tially effective in preventing intimal lesions. Histology of the nontr eated allografts showed ongoing acute rejection in the adventitial lay er. The degree of cellular infiltration correlated with the severity o f arteriosclerotic lesions. High dose CsA and RAPA treatment prevented adventitial infiltration in both models, while low dose CsA was only moderately effective. In conclusion, in the present study, the degree of arteriosclerotic involvement after allogeneic aorta transplantation was related to the severity of cellular adventitial infiltration. The myointimal thickening was inhibited by effective immunosuppressive tr eatment. These observations may imply that chronic rejection develops after ineffective immunosuppression.