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-deox yspergualin (DSG) administration against acute rejection of canine pan creatic allografts. Subsequent to partial pancreatic allotransplantati on and total extirpation of the pancreas, 20 adult mongrel dogs were d ivided 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 (gro up 3, n = 5), or DSG at 5.0 mg/kg/day (group 4, n = 5) on postoperativ e days 4-7. The graft survival, defined by a fasting serum glucose lev el <150 mg/dl, was significantly prolonged from 6.2 +/- 1.2 days in gr oup 1 to 12.4 +/- 2.7 days in group 3 (p < 0.05) and to 16.8 +/- 3.2 d ays in group 4 (p < 0.05). Graft survival was not significantly prolon ged in group 2, however. Two normoglycemic dogs in group 4 died due to gastrointestinal toxicity, one of the most serious side effects of DS G. The observation that the serum insulin levels increased in dogs tre ated with DSG was compatible with dose-dependent graft survival and su ggested that DSG had no toxic effects on pancreatic endocrine function . In group 1 significantly increased thromboxane B-2 (TXB(2)) levels a nd TXB(2)/6-keto-prostaglandin F-1 alpha (PGF(1 alpha)) ratios were ob served on postoperative days 3-5 which was thought to reflect acute re jection. Following administration of DSG, both TXB(2) levels and TXB(2 )/PGF(1 alpha) ratios were decreased on the 5th postoperative day in g roups 2-4. The decreased TXB(2) levels in group 4 and the decreased TX B(2)/PGF(1 alpha) ratios in groups 3 and 3 were significantly differen t from the control group (group 1) on the 5th postoperative day. We co nclude that DSG is effective in delaying rejection when administered t herapeutically and that its activity may correlate with decreased TXB( 2) concentrations.