CYCLOSPORINE SUPPRESSES TRANSPLANT ARTERIOSCLEROSIS IN THE AORTA-ALLOGRAFTED, CHOLESTEROL-CLAMPED RABBIT - SUPPRESSION PRECEDED BY DECREASEIN ARTERIAL LIPOPROTEIN PERMEABILITY

The immunosuppressant cyclosporin has been suggested to aggravate as w ell as retard the development of transplant arteriosclerosis, the majo r long-term problem for patients with heart transplants. We examined t he effect of human therapeutic levels of blood cyclosporin on the deve lopment of experimental transplant arteriosclerosis. The thoracic aort a from one rabbit was transplanted as an end-to-side bypass on the abd ominal aorta of another rabbit, and plasma cholesterol was clamped at 5 to 7 mmol/L. Cyclosporin markedly suppressed the severity of transpl ant arteriosclerosis, judged both biochemically and histologically: ch olesterol content in aortic transplants was reduced by 70% and 80% aft er 10 days and 20 days of cholesterol feeding, respectively (both comp arisons, P<.01), and after 20 days of cholesterol feeding myointimal p roliferation was totally inhibited in grafts from cyclosporin-treated animals, judged from maximal intimal thickness and intimal area on cro ss sections of grafts (both comparisons, P<.05). In another group of n on-cholesterol-fed, aorta-transplanted rabbits, cyclosporin reduced by 90% (P<.01) an otherwise markedly increased permeability to low-densi ty lipoprotein in transplanted aortas. These results suggest that cycl osporin causes a substantial decrease in the severity of transplant ar teriosclerosis and that this effect is mediated at least partly via a large decrease in aortic lipoprotein permeability.