2007 Fiscal Year Final Research Report Summary
Amelioration of liver graft viability by improvement of sinusoidal microcirculation
| Project/Area Number |
18591404
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Akita University |
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Principal Investigator |
MIYAZAWA Hideaki Akita University, School of Medicine, Assistant Professor (10323148)
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| Project Period (FY) |
2006 – 2007
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| Keywords | sinusoidal microcirculation / sinusoidal collapse / non-heart-beating donor / continuous perfusion / liver transplantation |
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| Research Abstract |
[Introduction] Non-heart-beating donor (NHBD) livers are anticipated as an additional source of grafts to solve chronic shortage of donors. Uncontrolled NHBD graft usually suffers from an extensive injury of warm ischemia, and the transplantation therefore results in poor outcomes. To make a point for preserving NHBD livers clear, we compared post preservation damage of NHBD livers using three solutions available at present, UW, HTK, and ET-Kyoto (ETK) solutions.
[Methods] Wistar rats underwent phrenotomy and livers were retrieved 60 or 30 minutes after cardiac arrest. Urokinase solution was injected via the portal vein in order to dissolve thrombi in sinusoid, then the livers were left 10 minute at room temperature. The livers were flushed by 80ml of cold UW or HTK or ETK solution, and preserved in the respective solution for 8 hours at 4℃. HBD liver without preservation was used as control. We assessed graft viability using isolated liver perfusion model. After 20-minute rewarming, li
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vers were perfused by oxygenated Krebs Henseleit Buffer. Perfusion was carried out for 60 minutes. Portal venous pressure and bile production were monitored during perfusion. AST level in the perfusate was measured. Apoptosis was evaluated by TUNEL staining.
[Results] The injection of urokinase solution improved graft viability. Portal venous pressure was lower in ETK group than UW and HTK groups. ETK group produced more bile during 60-minute reperfusion than UW and HTK groups. There was significant difference between ETK group and UW group. However, bile production in ETK group was only one-third of HBD livers. The level of AST in the perfusate was lower in ETK group than UW and HTK groups. There was significant difference only in 5 minute after reperfusion between the groups of UW and ETK. In H-E staning, hepatocyte shrank markedly in the UW group, resulting in remarkable extension of sinusoidal space. On the other hand, in the HTK group, the liver architecture was better preserved. A higher osmolarity of UW solution might, in converse, facilitate the damage in the pre-injured hepatocytes in NHBD livers. TUNEL staining after 8-hour cold storage. In HTK group, in spite of preserved architecture, there appeared many TUNEL positive hepatocytes diffusely. Conversely, only a few TUNEL positive cells were noticed in UW group, despite hepatocytes showed marked shrinkage.
[Conclusion] Instead of HBD livers, higher osmolarity of UW solution may be harmful in the preservation of NHBD livers. In NHBD graft, limitation of apoptosis during cold preservation did not necessarily contribute to maintaining a better graft viability. ETK solution seemed to have advantage, compared with HTK solution. However, ETK solution was enough to maintain NHBD graft viability. A better strategy in preservation method for salvaging NHBD livers is necessary. Less
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Research Products
(2 results)
