Beneficial effect of FR183998, a Na+/H+ exchanger inhibitor, on porcine pancreas allotransplantation retrieved from non-heart-beating donors.
Activation of Na(+)/H(+) exchanger (NHE) may have an important role in the ischemia/reperfusion injury by producing intracellular calcium overload. Recent studies have shown a beneficial effect of an NHE inhibitor on the ischemia/reperfusion injury in the heart. In this study, we examined the effect of FR183998, a potent NHE inhibitor, in porcine pancreas allotransplantation from non-heart-beating Landrace pig donors (NHBDs). The four experimental groups included: untreated with no preservation (group 1; n = 3), treated with no preservation (group 2; n = 5), untreated with preservation (group 3; n = 6), and treated with preservation (group 4; n = 4). The preservation was made in ice-cold University of Wisconsin (UW) solution for 24 hours. The groups treated received 1 mg/kg FR183998 before donor cardiac arrest and 10 mg in the UW solution flush in situ. Serum blood glucose, insulin, and amylase were measured daily. An intravenous glucose tolerance test (IVGTT) was performed on the postoperative day (POD) 7 when pigs were sacrificed for histological examination. Graft survival rates on that day in groups 1,2,3, and 4 were 3 of 3; 5 of 5; 3 of 6; and 4 of 4, respectively. The mean K values of IVGTT in groups 3 and 4 were 0.78 +/- 0.10 and 1.27 +/- 0.16, respectively, which were significantly different (P < .05). Upon histological examination, pancreatic tissue in group 3 showed more severe edema and necrosis than other groups. FR183998 may be considered beneficial for ischemia/reperfusion injury to pancreatic grafts from NHBDs.
Masuoka
H
H
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan. masuoka@mail.tains.tohoku.ac.jp
Fujimori
K
K
Sekiguchi
S
S
Watanabe
M
M
Wang
H
H
Aiso
T
T
Yamaya
H
H
Satoh
A
A
Satomi
S
S
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001926:Brain Death; D005951:Glucose Tolerance Test; D005978:Glutathione; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology*; D007328:Insulin; D019188:Organ Preservation Solutions; D016035:Pancreas Transplantation / Q000379:methods / Q000502:physiology*; D011887:Raffinose; D015427:Reperfusion Injury / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013552:Swine; D013876:Thiophenes / Q000494:pharmacology*; D014021:Tissue Preservation; D014184:Transplantation, Homologous
D001786:Blood Glucose; C449400:FR 183998; D006146:Guanidines; D007328:Insulin; D019188:Organ Preservation Solutions; D017923:Sodium-Hydrogen Exchangers; D013876:Thiophenes; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose