Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids

Abstract

Improved survival of segmental pancreatic homografts has been obtained in animals using cyclosporine alone for immunosuppression [1,2]. Despite this, the results in clinical trials of pancreas transplantation have remained poor, in part because effective ways of draining or eliminating the exocrine drainage of the segmental grafts have not been developed [3]. Herein we report our experience in dogs with the alternative procedure of total pancreaticoduodenal homotransplantation using cyclosporine combined with small doses of steroids. Material and MethodsTwenty mongrel dogs of both sexes weighing between 15 and 25 kg were used as donors or recipients in 10 experiments. The homografts were removed from the donor through a midline incision. The transplant specimen was prepared, preserving the splenic vessels out to their entry into the spleen at the site of splenectomy and retaining the hepatic artery throughout its course, including its termination as the gastroduodenal artery (Figure 1, top). The splenic, superior mesenteric, and portal veins were retained with the specimen which included both lobes of the pancreas as well as the duodenum. The composite organ graft was flushed through the celiac axis with chilled, modified Collin's solution (Travenol) and preserved for 2 to 3 hours.The organ complex was revascularized in the left iliac fossa with end-to-side anastomoses of the donor celiac axis and portal vein, to the recipient iliac vessels (Figure 1, above). The proximal duodenum of the graft was closed, and the distal end was anastomosed end-to-side to the proximal recipient jejunum. Either then or a few days later, the recipient dog underwent total pancreaticoduodenectomy. Gastrointestinal reconstruction was performed with cholecystojejunostomy and gastrojejunostomy (Figure 1, right).All dogs were given intravenous fluids, penicillin, and gentamicin for 5 days postoperatively. The animals were allowed to drink water ad libitum after the second postoperative day and to eat solid food after the fifth postoperative day. Immunosuppression consisted of cyclosporine at an oral dose of 17 mg/kg per day beginning on the day after operation, and prednisone, 0.5 mg/kg per day. Fasting glucose concentrations in the venous plasma were measured daily during the first postoperative week and 3 times a week thereafter. Intravenous glucose tolerance tests were performed in two dogs who survived more than 60 days. The homografts were sampled at the time of sacrifice or at autopsy. TheRequests for reprints should be addressed to Thomas E. Starzl, MD,