Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046

Abstract

Prostanoids, such as prostacyclin (PGI) and thromboxane A2 (TxA), have been recently suggested to play an important role in preservation-induced injury of pancreas grafts. We have previously shown that the TxA synthesis inhibitor OKY046 prevents a decrease of both the PGI/TxA ratio and blood flow in pancreas grafts after 24-hr preservation with Euro-Collins solution. In our present study, we analyzed whether OKY046 added to University of Wisconsin (UW) solution could extend successful cold-storage preservation of segmental canine pancreas grafts, compared with UW alone. We divided 30 dogs into four preservation groups: Group 1, UW solution for 72 hr ( n = 7); Group 2, UW solution for 96 hr ( n = 8); Group 3, UW solution plus OKY046 (10 −4 M) for 72 hr ( n = 7); and Group 4, UW solution plus OKY046 (10 −4 M) for 96 hr ( n = 8). After the cold storage period, segmental pancreas autotransplantation with immediate completion pancreatectomy was done. Preservation was deemed successful if serum glucose < 150 mg/dl was maintained for at least 5 days. Intravenous glucose tolerance tests and biopsies were done in those dogs with functioning grafts 14 days post-transplant. Successful preservation rates were as follows: Group 1, 57.1%; Group 2, 12.5%; Group 3, 100%; and Group 4, 75%. The mean K values (± standard error) were: Group 1, 1.54 ± 0.13; Group 2, 0.59; Group 3, 1.54 ± 0.14; and Group 4, 1.59 ± 0.24 (not statistically different). In contrast, the initial insulinogenic indices of both Group 3 (0.066 ± 0.008) and Group 4 (0.113 ± 0.022) were significantly higher than in Group 1 (0.054 ± 0.006) ( P < 0.05). In addition, pancreas biopsies showed almost normal architecture of both endocrine and exocrine cells in Group 4, but considerable fibrosis in Group 2. We conclude that adding OKY046 in UW solution results in good viability after prolonged cold storage and extends successful pancreas preservation to 96 hr in the canine autotransplant model.