PROLONGATION OF SEGMENTAL PANCREATIC ALLOGRAFTS IN DOGS RECEIVING CYCLOSPORIN A

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Abstract
This study showed that a heterotopic autotransplant of the tail of the pancreas was capable of maintaining adequate glucoregulatory function in pancreatectomized dogs, glucose tolerance test curves, and K values not differing from normal dogs 4 months after transplantation. Hyperinsulinemia in the fasting state was observed in the absence of hypoglycemia in auto graft and allograft recipients. Intraductal Ethibloc injection produced total replacement of the exocrine gland at 4 months by fibrosis but with the preservation of islets. Cyclosporin A (Cy A, oral drinking solution) in a dose of 25 mg/kg/day given to recipients of heterotopic segmental allografts produced a slight but significant prolongation of graft survival, but a dose of 40 mg/kg/day resulted in indefinite graft survival (>100 days) in five of eight allograft recipients. During intravenous glucose tolerance tests (IVGTTs), fasting hyperinsulinemia and significantly impaired glucose degradation (K values) was observed in long-term surviving allograft recipients 4 months after transplantation. In four long-term surviving pancreatic allograft recipients initially given 40 mg/kg/day, the dose of Cy A was gradually reduced after 4 months to a maintenance dose of 5 mg/kg/day by 6 months. On a dose of 5 mg/kg/day, three dogs rejected their grafts between 18 and 28 days after this schedule had commenced. Successful reversal of the hyperglycemia in two of three dogs that rejected their grafts was achieved by i.v. methylprednisolone and increased doses of Cy A. These results indicate that Cy A alone could significantly prolong the survival of canine pancreatic segmental allografts, but initially higher doses were required than that found to be effective in prolonging renal allograft survival in the dog.

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