11 research outputs found
A comparison of the effects of rapamycin and cyclosporine on kidney and heart morphology in a rabbit heterotopic heart transplant model
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
A comparison of cyclosporine A and cyclosporine G in a rabbit heterotopic cardiac transplant model: graft outcome and histological findings
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