Effect of cyclosporin A on allotransplanted pancreatic fragments to the spleen of totally pancreatectomized dogs.

Cyclosporin A (Cy A) was evaluated in dogs to assess its effectiveness of prolonging survival of allogeneic pancreatic islet tissue transplanted to the spleens of totally pancreatectomized mongrel dogs. Thirty-seven dogs were made diabetic by total pancreatectomy. Ten untreated pancreatectomized animals survived a mean (+/-SE) of 6.3 +/- 0.9 days and died with mean (+/-SE) plasma glucose levels of 23.2 +/- 2.7 mmol/liter. Dispersed pancreatic fragments, prepared by collagenase digestion without separation of exocrine and endocrine components, were directly implanted into the splenic pulp of 27 pancreatectomized dogs. Twelve dogs given autotransplants became normoglycemic after 4.3 +/- 0.5 days and remained so until killed at 60 days post-transplant, although normal glucose tolerance tests were not achieved. Eight nonimmunosuppressed dogs given allogeneic pancreatic fragments did not become normoglycemic but survived for 13.0 +/- 2.1 days, the dogs dying with a terminal plasma glucose of 22.7 mmol/liter. An additional seven dogs given allogeneic transplants were given Cy A (oral solution), 25 mg/kg/day, for 14 days, and, although failing to become normoglycemic, survived for 28.1 +/- 5.4 days and died with terminal plasma glucose levels of 25.1 +/- 0.6 mmol/liter. Intrasplenic complications included subcapsular hematomas, intrasplenic necrosis and cavitation, capsular perforations, and arteriolar thrombosis. The failure to achieve normoglycemia with allogeneic dispersed pancreatic tissue in dogs treated with Cy A and the complications associated with the implantation of the tissue in the spleen do not suggest that this approach is worthy of clinical trial.