A comparison of cyclosporine A and cyclosporine G in a rabbit heterotopic cardiac transplant model: graft outcome and histological findings

Abstract

Cervical heterotopic heart transplants were performed on 20 male New Zealand white rabbits comprising 4 treatment groups. Animals in each group were injected daily via the marginal ear vein and received one of the following regimes: Cyclosporine A, 10 mglkglday; Cyclosporine G, 15 mglkglday; cremophor-El, 3mllday; or normal saline. Measurement of 24 hour trough blood concentrations revealed no significant differences between the average concentrations of Cyclosporine A and Cyclosporine G. Animals were examined daily and the cervical allografts assessed by palpation for viabilitylrejection. The duration of the study ended for each animal when the graft stopped beating at which time the animals was euthanized and the transplanted heart and native kidneys harvested and processed for light microscopy evaluation of rejection and drug toxicity, respectively. Graft survival in the Cyclosporine A group significantly surpassed that seen in the Cyclosporine G group as well as the control groups, whereas in animals treated with Cyclosporine G, graft survival was not different from controls. In the native kidney, there were no differences in glomerular tuft area or volume density amongst drug-treated or control animals. In contrast, tubule atrophy and interstitial fibrosis were markedly greater in Cyclosporine A-treated vs Cyclosporine Gtreated animals. The results of this study indicate that, whereas Cyclosporine G is less nephrotoxic than Cyclosporine A, given equivalent blood concentrations Cyclosporine A delays rejection of a cardiac allograft significantly longer than Cyclosporine G in this animal species.