raffinose and ozagrel

Topics: Adenosine; Allopurinol; Animals; Dogs; Enzyme Inhibitors; Female; Glucose; Glutathione; Graft Survival; Heart; Heart Transplantation; Insulin; Kidney; Kidney Transplantation; Male; Mannitol; Methacrylates; Organ Preservation; Organ Preservation Solutions; Organ Specificity; Pancreas; Pancreas Transplantation; Potassium Chloride; Procaine; Raffinose; Rats; Rats, Wistar; Thromboxane-A Synthase; Time Factors

We have shown that 5-hr preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C allows ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. However, 8 hr of preservation using this method caused a disturbance of vascular microcirculation and did not resuscitate the grafts. The aim of this study was to examine the effect of thromboxane A2 synthesis inhibitor OKY046 on vascular endothelial cells and ATP tissue levels of canine pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C, and vascular microcirculation and pancreas viability after transplantation. Graft viability was judged by graft survival following autotransplantation. ATP tissue levels were measured by high-performance liquid chromatography at the end of preservation. Viability of the vascular endothelial cells was judged using nuclear trypan blue uptake of the graft after preservation. Pancreatic tissue perfusion was measured using an H2 clearance technique after reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). However, 5-hr preservation made it possible to recover the pancreas (5/5); 8-hr preservation was not successful (0/3). ATP tissue levels after 5-hr and 8-hr preservation were 9.40+/-2.09 and 7.37+/-1.06 micromol/g dry weight, respectively, and OKY046 did not affect ATP synthesis during 8-hr preservation (8.44+/-0.92 micromol/g dry weight). The percentage of nuclear trypan blue uptake of endothelial cells in 8-hr-preserved grafts was 37.6+/-11.6% and was significantly higher than the value in 5-hr-preserved grafts (5.0+/-3.0%; P<0.01). However, OKY046 significantly reduced trypan blue uptake in 8-hr-preserved grafts (8.2+/-3.6%; P<0.01). Pancreatic tissue perfusion in 8-hr-preserved grafts after 2 hr of reperfusion was 28.5+/-7.5 ml/min/100 g, and was significantly lower than the value in 5-hr-preserved grafts (57.1+/-4.4 ml/ min/100 g; P<0.01), but OKY046 dramatically improved pancreatic tissue perfusion (97.1+/-14.6 ml/min/100 g; P<0.01). As a consequence, 8-hr-preserved grafts were resuscitated (4/5). We conclude that OKY046 protects the vascular endothelium during preservation by the two-layer method at 20 degrees C and consequently improves vascular microcirculation on reperfusion. Together with ATP synthesis, which is essential for repairing damaged cells, the canine p

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Dogs; Endothelium, Vascular; Enzyme Inhibitors; Female; Glutathione; Graft Survival; Insulin; Ischemia; Male; Methacrylates; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Perfusion; Raffinose; Temperature; Thromboxane A2; Time Factors; Trypan Blue

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Dogs; Female; Glutathione; Graft Survival; Insulin; Male; Methacrylates; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Pancreatic Ducts; Raffinose; Time Factors; Transplantation, Autologous

Topics: Adenosine; Allopurinol; Animals; Dogs; Female; Glutathione; Insulin; Kidney Transplantation; Liver; Male; Methacrylates; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Raffinose; Solutions; Thromboxane A2; Thromboxane-A Synthase; Time Factors

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 auto-transplantation with immediate completion pancreatectomy was done. Preservation was deemed successful if serum glucose less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Dogs; Epoprostenol; Female; Glutathione; Insulin; Male; Methacrylates; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Raffinose; Solutions; Thromboxane-A Synthase; Thromboxanes; Time Factors