Effects of Na+/H+ exchanger inhibitor to ischemic-reperfusion injury in non-heart beating pancrea graft

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671211
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Tohoku University
• Principal Investigator: FUJIMORI Keisei Tohoku Univ., Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50238622)
• Co-Investigator(Kenkyū-buntansha): SUGAWARA Koh Tohoku Univ., School of Medicine Hospital, Research Associate, 医学部附属病院, 助手 (30291256) ; SATO Akira Tohoku Univ., School of Medicine Hospital, Lecturer, 医学部附属病院, 講師 (20250764) ; DOI Hideyuki Tohoku Univ., School of Medicine Hospital, Associate Professor, 医学部附属病院, 助教授 (90188839) ; KOYAMADA Nozomi Tohoku Univ., School of Information Sciences, Research Associate, 大学院・情報科学研究科, 助手 (80302149)
• Project Period (FY): 2001 – 2002
• Keywords: ischemic reperfusion injury / pancreas transplantation / NHE exchanger inhibitor / pig pancreas allotransplantation / rat pancreas reperfusion model / islet / 膵ラ島

Research Abstract

In pHi recovery after the NH4C1 prepulse technique in Wister rat pancreatic islets, FR183998 showed an effect of a potent Na+/H+ exchanger inhibitor. An inhibition of intracellular Ca2+ overload was not evaluated in Fura-2 fluorescence signals. FR effects In the tail segment of rat ischemic models, the FR were not evaluated from pancreatic duct injury. In more than 90 min. of the whole pancreas ischemia, administration of FR before ischemia ameliorates edema after reperfusion. The pancreatic tissue PO2 with LICOX after reperfusion, FR group showed high PO2 value in more than 90 min. ischemia, though there is not statistically significant. Pigs (20-25kg) are used as the pancreatic allotransplantation model. Pancreas grafts are retrieved from non-heart beating donors after 60 minutes periods of cardiac arrest. Grafts were preserved in the UW solution at 4°C for 24 hours. Blood glucose, IRI, s-and u-amylase was examined at every postoperative day. IVGTT test was performed at 7 POD. Graft ATP measurement and histological examination was performed. FR iv injection and perfusion of the UW solution added FR ameliorated interstitial edema. Graft survival rate in the FR group, which graft is administered FR before 60 minutes normothermic ischemia and stored 24 hours in UW solution added FR, was significantly higher than in the non-FR group. In conclusion, it was suggested that Na+/H+ exchanger inhibitor, FR 183998, improves normothermic and hypothermic ischemia-reperfusion injury to some extent, though a relationship with intracellular Ca2+ concentration could not be revealed.