Immunosuppression in rabbits: skin and kidney allografts

Green, C. J.

doi:10.1258/002367775780994547

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…Animals were either treated for; short periods (Green & Allison, 1978;Green et al, 1982;Neild, Ivory & Williams, 1983Neild et al, 1983a;Diperink & Starklint, 1984;King, Clunie & Dumble, 1984) or the 'normal' dose was thought to be 30 mg/kg orally daily (Ryffel et al, 1983). As we know today, this dose is well below the therapeutic range.…”

Section: Laboratory Testsmentioning

confidence: 99%

Cyclosporine toxicity in rabbits

et al. 1986

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213Summary Rabbits treated with an immunosuppressive dose of cyclosporine for a prolonged period of time developed a clinically distinct toxic syndrome characterized by wasting, loss of weight, reduced food and water consumption and reduced movement. Ultimately 74 of 153 animals died within 60 days of treatment with a distended stomach and intestines full of dry undigested food. The syndrome was dose dependent but seemed unrelated to the route of administration. It occurred in two strains and two different colonies. No infectious agent was implicated. Histological examination and a variety of laboratory tests did not elucidate the syndrome. It could not be prevented by drugs that increased bowel movement or gastric emptying and was more pronounced in animals given additional indomethacin. Reduction of cyclosporine dose reduced toxicity but at the expense of reduced immunosuppression. We were unable to define a therapeutic non-toxic range by serial determination of cyclosporine blood concentrations. This highlights the difficulty in obtaining a therapeutic dosage level in rabbits on long-term cyclosporine immunosuppression.

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Section: Laboratory Testsmentioning

confidence: 99%

Cyclosporine toxicity in rabbits

et al. 1986

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Vascularized whole knee joint allografts in rabbits immunosuppressed with cyclosporin A

Siliski

Simpkin²,

Green³

1984

Arch. Orth. Traum. Surg.

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To develop the surgical model, whole knee joints including the distal femur, proximal tibia, and joint capsule, were raised on a vascular pedicle and then replanted at the same site. Rigid fixation of the bones was achieved using two mini-plates on the tibia and femur. Revascularization of the knee was accomplished by end-to-end anastomosis of the popliteal vessels using standard microvascular techniques, and the vascular and neural supplies to the lower leg and foot were preserved. A total of 21 vascularized whole knee allografts were then similarly performed on a microvascular pedicle between two incompatible strains of rabbit. In a control group of six adult animals, no immunosuppression was administered. Two of these joints were harvested at 1 week and had patent popliteal arteries. The remaining four joints were harvested at 2-3 weeks when they were deteriorating and were found to have occluded popliteal vessels by arteriography. Eight adult allograft recipients were immunosuppressed with cyclosporin A (CyA) at 15 mg/kg per day. One allograft failed at 10 days due to femoral fracture. None of the remaining seven were rejected acutely, and three of them had patent vessels by arteriography and live bone and cartilage by light microscopy when harvested 100 days after transplantation. In another group, seven knee joints were allografted into immature rabbits immunosuppressed with CyA. Again, none rejected acutely, and 90 days later two of the seven allografts had patent vessels by arteriography, growth by serial radiographs, and live bone and cartilage by histological examination. This pilot study suggests that CyA will be useful as an immunosuppressive agent in the study of vascularized bone and cartilage transplantation, and that experimental epiphyseal plate allografting is possible in rabbits.

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