LONG-TERM NORMOGLYCEMIA IN PANCREATECTOMIZED DOGS FOLLOWING PANCREATIC ISLET ALLOTRANSPLANTATION AND CYCLOSPORINE IMMUNOSUPPRESSIONxs

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 .mu.g/L), or high CsA (600-1000 .mu.g/L). While AP and low CsA failed to delay rejection, high CsA achieved prolonged (> 100 days) graft function in 5 of 12 dogs, with a median duration of 85.5 days. (P < .01 vs. AP and low CsA). While no interference with islet engraftment was seen in CsA-treated dogs, late graft failure (> 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 .mu.g/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.