Long-term normoglycemia in pancreatectomized dogs following pancreatic islet allotransplantation and cyclosporine immunosuppression.
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.
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
D001786:Blood Glucose; D003524:Cyclosporins; D007328:Insulin; D001379:Azathioprine; D011241:Prednisone