A comparison of the effects of rapamycin and cyclosporine on kidney and heart morphology in a rabbit heterotopic heart transplant model

Abstract

Rapamycin (RAPA) or cyclosporine (CsA) was administered intravenously, daily for 60 days, to rabbits with heterotopic heart transplants. Groups of 5 rabbits were randomly assigned to receive RAPA at 0.05,O. 1,0.5 or 1 .O mg/kglday or CsA at either 5 .O, 10.0 or 15 mg/kg/day. Dmg vehicle and saline controls were also included. Animals were examined daily and the cervical allografts assessed by palpation for viabilitylrejection. In those animals in which the heart stopped beating, the heart was removed and processed for light microscopic evaluation. The duration of the study was for 60 days at which time the animals were sacrificed and the transplanted heart and native kidneys removed and processed for light microscopic assessment of rejection and drug toxicity respectively. Biochemical and functional parameters in these animals were previously reported (Transplantation 5: 340-345, 1993). Animals that rejected their grafts were maintained on the dmg until the endpoint of the study to assess toxicity in the native kidneys. The rejected hearts from these animals were also harvested for microscopic evaluation. The results of the study revealed that heart rejection in drug treated animals was significantly lower than in corresponding controls but not different among the various drug treated groups. In the kidney, there were no differences in glomerular tuft area or tuft volume density amongst drug-treated or control animals. In contrast, tubule atrophy and interstitial fibrosis were markedl 3 greater in CsA-treated vs RAPA-treated animals (X 5.00, pe0.02). These data suggest that whereas drug efficacy with respect to heart allograft viability is similar between CsA and RAPA, renal toxicity is significantly less in those animals receiving RAPA