Ra. Geerling et al., SUPPRESSION OF ACUTE REJECTION PREVENTS GRAFT ARTERIOSCLEROSIS AFTER ALLOGENEIC AORTA TRANSPLANTATION IN THE RAT, Transplantation, 58(11), 1994, pp. 1258-1263
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.