Relative importance of ischemic injury and immunological injury on the development of transplant arteriosclerosis in rabbit aortic allografts.

The development of transplant arteriosclerosis has emerged as a major problem to long-term survival after heart transplantation. The accelerated development of arteriosclerosis in the transplanted arteries, including the aorta, could result either from an ischemic injury in connection with the transplantation, or from an immunological reaction against the transplant, or both. We evaluated histologically and biochemically whether extension of the ischemic period from 1 to 24 hr has any influence on the development of transplant arteriosclerosis, in aorta-allografted rabbits clamped at human levels of plasma cholesterol. One set of rabbits was without immunosuppressive treatment (n = 10 + 9) and another otherwise identical set of rabbits received cyclosporine to achieve blood cyclosporine levels in the human therapeutic range (n = 10 + 12). The number of T lymphocytes in intima suggested that, in the grafts from untreated animals, an immunological injury had arisen, which cyclosporine reduced. A clear trend toward a worsening of the transplant arteriosclerosis was demonstrated as a function of the severity of the ischemic injury, both with and without immunosuppressive treatment. However, the worsening effect of maximal ischemic injury was less than that due to maximal immunological injury. In grafts from cyclosporine-treated animals, the development of transplant arteriosclerosis was significantly less than in grafts from untreated animals exposed to identical periods of ischemia. These results suggest that compared with immunological injury, ischemic injury is of minor importance for the development of experimental transplant arteriosclerosis.