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

Seikon Kin, Edic Stephanian, Paul Gores, Ken Shirabe, Tsuneo Tanaka, Anastasio Salazar, Kenneth Brayman, Rainer W G Gruessner, David E R Sutherland

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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.

Original languageEnglish (US)
Pages (from-to)577-582
Number of pages6
JournalJournal of Surgical Research
Volume52
Issue number6
DOIs
StatePublished - 1992
Externally publishedYes

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Thromboxane A2
Canidae
Pancreas
Transplants
Dogs
Biopsy
Pancreatectomy
Endocrine Cells
Autologous Transplantation
Autografts
Epoprostenol
Glucose Tolerance Test
Prostaglandins
Fibrosis
Glucose
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Surgery

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Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046. / Kin, Seikon; Stephanian, Edic; Gores, Paul; Shirabe, Ken; Tanaka, Tsuneo; Salazar, Anastasio; Brayman, Kenneth; Gruessner, Rainer W G; Sutherland, David E R.

In: Journal of Surgical Research, Vol. 52, No. 6, 1992, p. 577-582.

Research output: Contribution to journalArticle

Kin, Seikon ; Stephanian, Edic ; Gores, Paul ; Shirabe, Ken ; Tanaka, Tsuneo ; Salazar, Anastasio ; Brayman, Kenneth ; Gruessner, Rainer W G ; Sutherland, David E R. / Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046. In: Journal of Surgical Research. 1992 ; Vol. 52, No. 6. pp. 577-582.
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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.",
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AU - Stephanian, Edic

AU - Gores, Paul

AU - Shirabe, Ken

AU - Tanaka, Tsuneo

AU - Salazar, Anastasio

AU - Brayman, Kenneth

AU - Gruessner, Rainer W G

AU - Sutherland, David E R

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N2 - 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.

AB - 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.

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