title: Long-term normoglycemia in pancreatectomized dogs following pancreatic islet allotransplantation and cyclosporine immunosuppression.
abstract: Pancreatectomized dogs received intrasplenic autotransplants or allotransplants of unpurified islets prepared from the pancreata of unrelated outbred dogs, by a standard collagenase ductal perfusion method. Allograft immunosuppression consisted of tapering azathioprine-prednisone (AP), low level cyclosporine (CsA, through whole blood high-pressure liquid chromatography (HPLC) level 300-600 micrograms/L), or high CsA (600-1000 micrograms/L). While AP and low CsA failed to delay rejection, high CsA achieved prolonged (greater than 100 days) graft function in 5 of 12 dogs, with a median duration of 85.5 days. (P less than .01 vs. AP and low CsA). While no interference with islet engraftment was seen in CsA-treated dogs, late graft failure (greater than 30 days) was seen in 3 of 6 CsA autografts and 5 of 12 high CsA allografts. CsA at whole-blood HPLC levels of 600-1000 micrograms/L can achieve prolonged normoglycemia in pancreatectomized canine recipients of islet allografts. The effects of such doses of CsA on islet function may be substantial.
mesh_terms: D000818:Animals; D001379:Azathioprine / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis*; D003524:Cyclosporins / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000187:drug effects; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation; D010180:Pancreatectomy; D011241:Prednisone / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D003524:Cyclosporins; D007328:Insulin; D001379:Azathioprine; D011241:Prednisone