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The Experimental Study Of A New Liver Allograft Preservation Solution

Posted on:2004-10-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:S H DongFull Text:PDF
GTID:1104360125965372Subject:Surgery
Abstract/Summary:PDF Full Text Request
Liver transplantation has become recognized as the standard treatment for end-stage liver diseases. Advancements in organ preservation over the past century have made liver transplantation becoming a powerful life saving therapy around the world. However, liver allograft shortage has been one of the barriers for clinical transplantation. Up to now, flushing the organ and storing it at low temperatures is the standard method for organ preservation. University of Wisconsin (UW) solution, Celsior solution (CS) and HTK solution are the conventional solutions for organ preservation. But all these solutions are expensive. The aim of this study is to dispensing a new liver allograft preservation solution(SWH solution) and compare it with UW solution.A new preservation solution was dispensinged in accordance with our formula. PH value of the solution is 7.9 + 0.1 and osmotic concentration is 340mmol/L. Adult SD rats of both sexes, weighing 200-230g, were used to establish orthotopic liver transplantation(OLT) animal model. Animals were randomized into two groups according to the difference in a preservation solution: the SWH and the UW group. Donor livers were flushed with the respective cold solution and stored in the respective solution at 4癈 for 8h(n=8), 12h(n=8), 18h(n=8) respectively. The animals were killed 1h(n=8) or 12h(n=8) for harvesting implanted liver and blood specimen respectively. Gross morphology and microscopic pathological changes of preserved liver and implanted liver were observed. Weight change after cold preservation of liver, ALT, AST and LDH value in preservation solution or blood, ATP, TAN and MDA content of the liver were measured. Apoptosis of hepatocytes, bile production of the implanted liver and 7-day survival rate of OLT rats were observed. Data are presented as mean+ standard error of the mean. The analysis of variance and x2 test were used. P<0.05 was considered statistically significant.The results revealed that livers flushed and preserved in SWH solution showed less structural abnormalities, such as hepatocytes swelling, necrosis, enlargement of Disse's spaceand hepatocyte apoptosis than that in UW solution. The weight of liver became lighter thanthat before preservation in UW solution, and statistically significant difference emerged. Butthe weight of liver became heavier than that before preservation in SWH solution and nostatistically significant difference emerged. ATP,TAN contents and EC in cold preserved liverdecreased rapidly with the prolongation of preserving period. ATP and EC increased rapidlyafter OLT, but TAN changed little. But the difference was not statistically significant in SWHand UW group. ALT, AST and LDH activity in preservation solution got higher lightly thanthat before preservation in two groups at 8h, 12h, 18h. Serum ALT, AST and LDH activitylevel were significantly higher than that before OLT in preservation solution(iJ<0.05).But nostatistically significant difference emerged in SWH and UW group. All six liver allograftspreserved in SWH and UW solution 8h secreted bile after implantation. Five out of 6 and fourout of 6 liver allografts preserved in SWH and UW solution 12h respectively secreted bileafter implantation, and no statistically significant difference emerged. If the liver allograftspreserved in SWH or UW solution for 18hrs, only 3 out of 6 allografts secreted bile afterimplantation. The content of MDA of liver allografts got higher lightly than that beforepreservation in SWH or UW group at 8h, 12h, 18h. But no no statistically significantdifference emerged. The content of MDA got significantly higher than that before OLT inthe two kind of preservation solutions(P<0.05). But no statistically significant differenceemerged in SWH and UW group(P>0.05). Apoptosis of hepatocytes occurred when theliver allografts preserved in SWH or UW solution for 8hrs and no statistically significantdifference emerged if preserved for 18hrs. Apoptosis index of hepatocytes increased heavilyafter liver allografts blood...
Keywords/Search Tags:rat, liver, preservation, UW solution, ischemia-reperfusion injury, transplantation apoptosis
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