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 mg/kg/day;
Cyclosporine G, 15 mg/kg/day;
cremophor-El, 3ml/day; 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 viability/rejection. The duration of the study ended for each animal when the graft stopped beating at which time the animals were 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 G-treated 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.