| Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Satoshi Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (20312580)
KAWAGICHI Naoki Tohoku Univ., Hospital, Research Associate, 病院・助手 (00333807)
DOI Hideyuki Tohoku Univ., Hospital, Associate Professor, 病院・助教授 (90188839)
MIYAZAKI Shukichi Tohoku Univ., Hospital, Lecturer, 病院・講師 (50282075)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Research Abstract |
We have developed new strategy for a successful liver transplantation from uncontrolled non-heart-beating donors (NHBD) or using extremely small for size grafts.
A.Rats were divided into five groups as follows ; 1)HB : livers were retrieved from heart-beating donors 2)NHB : livers were retrieved from NHBD 3)NM : from NHBD pretreated with nafamostat mesilate 4)FR : from NHBD pretreated with FR167653 5)FR+NM : from NHBD pretreated with FR167653 and nafamostat mesilate. In the NHB group, the values of IL-1β, TNF-a, thromboxane B2, leukotriene B4, and expressions of NF-κB, AP1, and cyclooxygenase-2 were significantly higher than those in the HB group. But in the FR+NM group those values were low, the structure of sinusoids was preserved and sinusoidal lumen was maintained histologically, the same findings were observed in the HB group. This combined treatment was quite effective in preserving sinusoid microcirculation in the liver grafts from NHBD.
B.We performed orthotopic liver transplanta
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tion using grafts from NHBD pretreated with nafamostat mesilate, FR167653 and OP2507(PGI2 analog : PG). Rats were divided into eight groups as follows ; 1)Control : without treatment 2)FR+PG+NM 3)FR+PG 4)FR+NM 5)PG+NM 6)FR 7)PG 8)NM. In the FR+PG+NM group and the FR+PG group, survival rate was significantly improved compared to the control group and the structure of sinusoids was preserved histologically. These combined treatments were quite effective in liver transplantation from NHBD.
C.Using pigs, the right lateral lobe, i.e. the 25% of the liver, was transplanted orthotopically. Pigs were divided into two groups ; graft without portacaval shunt (PCS)(n=11), and graft with PCS(n=11). Survival rate, portal flow, hepatic arterial flow and histological findings were investigated. The portal flow after transplantation in the group without PCS were increased 2.4 times, but the arterial flow were decreased. In the group without PCS, all pigs except for one died of liver dysfunction within 24 hours after transplantation. On the other hand, in the group with PCS, the portal flow were decreased after transplantation, but the arterial flow were increased 1.5 times. In the group with PCS, eight pigs survived for more than 4 days. These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury. Less
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