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Treatment of type I diabetes by early pancreas transplantation requires the availability of a safe and effective transplantation technique. With the currently available immunosuppressive drugs it is difficult to obtain long-term pancreatic allograft survival. In this respect pancreas grafts compare unfavorably with heart or kidney grafts. Using a relatively simple and safe subcutaneous transplantation technique we investigated the effect of blood transfusions combined with low-dose immunosuppressive drugs in rats and dogs in order to attain an immunosuppressive schedule of low toxicity. Subcutaneous pancreas transplantation appeared to be a feasible technique, with long-term graft survival in syngeneically transplanted rats and autotransplanted dogs. Only a moderate prolongation of pancreatic allograft survival by blood transfusions was demonstrated in both models. In rats one or three preoperative donor-specific blood transfusions significantly prolonged pancreas graft survival to 23 +/- 15 and 29 +/- 15 days, respectively, compared with 12 +/- 2 days in untreated controls. Low-dose cyclosporine (15 mg/kg on the day of operation) led to improved graft survival in nontransfused recipients (17 +/- 4 days), however, this treatment could not further prolong graft survival in transfused animals (34 +/- 20 days). In dogs, treated postoperatively with azathioprine and prednisolone, three preoperative third-party blood transfusions led to 29 +/- 19 days of pancreas graft survival, which was not significantly different from nontransfused controls (17 +/- 5 days). These results indicate that, in rats as well in dogs, pancreatic allografts are less sensitive to the immunomodulating effect of blood transfusions than heart and kidney grafts.
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