Increased graft survival by utilization of 15-deoxyspergualin in a canine pancreatic allotransplantation model.
The purpose of this study was to evaluate the effectiveness of 15-deoxyspergualin (DSG) administration against acute rejection of canine pancreatic allografts. Subsequent to partial pancreatic allotransplantation and total extirpation of the pancreas, 20 adult mongrel dogs were divided into four groups and treated with saline (group 1, controls, n = 5), DSG at 1.0 mg/kg/day (group 2, n = 5), DSG at 3.0 mg/kg/day (group 3, n = 5), or DSG at 5.0 mg/kg/day (group 4, n = 5) on postoperative days 4-7. The graft survival, defined by a fasting serum glucose level < 150 mg/dl, was significantly prolonged from 6.2 +/- 1.2 days in group 1 to 12.4 +/- 2.7 days in group 3 (p < 0.05) and to 16.8 +/- 3.2 days in group 4 (p < 0.05). Graft survival was not significantly prolonged in group 2, however. Two normoglycemic dogs in group 4 died due to gastrointestinal toxicity, one of the most serious side effects of DSG. The observation that the serum insulin levels increased in dogs treated with DSG was compatible with dose-dependent graft survival and suggested that DSG had no toxic effects on pancreatic endocrine function. In group 1 significantly increased thromboxane B2 (TXB2) levels and TXB2/6-keto-prostaglandin F1 alpha (PGF1 alpha) ratios were observed on postoperative days 3-5 which was thought to reflect acute rejection. Following administration of DSG, both TXB2 levels and TXB2/PGF1 alpha ratios were decreased on the 5th postoperative day in groups 2-4.(ABSTRACT TRUNCATED AT 250 WORDS)
Kitabayashi
K
K
2nd Department of Surgery, School of Medicine, Kanazawa University, Japan.
Izumi
R
R
Konishi
K
K
Shimizu
K
K
Miyazaki
I
I
D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D007328:Insulin / Q000097:blood; D008297:Male; D008954:Models, Biological; D016035:Pancreas Transplantation / Q000502:physiology; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014184:Transplantation, Homologous
D006146:Guanidines; D007166:Immunosuppressive Agents; D007328:Insulin; D013929:Thromboxane B2; C037258:gusperimus