Subnormothermic Machine Perfusion at Both 20掳C and 30掳C Recovers Ischemic Rat Livers for Successful Transplantation

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• 作者：Herman Tolboom ; M.D.² ; Maria-Louisa Izamis ; Ph.D.² ; Nripen Sharma ; Ph.D. ; Jack M. Milwid ; M.Sc. ; Basak Uygun ; Ph.D. ; Fran&ccedil ; ois Berthiaume ; Ph.D. ; Korkut Uygun ; Ph.D. ; Martin L. Yarmush ; M.D. ; Ph.D. ; ^{ireis@sbi.org}
• 关键词：liver transplantation ; reperfusion injury ; sub-normothermic machine perfusion
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：1 June, 2012
• 卷：175
• 期：1
• 页码：149-156
• 文件大小：1835 K

摘要

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lass="h4">Background

Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37掳C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20掳C and 30掳C.

lass="h4">Methods

Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1)聽WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20掳C, (4) 30掳C, and (5) 37掳C. Long-term graft聽performance was evaluated for 28 d post-transplantation. Acute graft performance was evaluated聽during a 2 h normothermic sanguineous reperfusion ex vivo. Fresh livers with 5 h of SCS were positive transplant controls while fresh livers were positive reperfusion controls.

lass="h4">Results

Following machine perfusion (MP) (Groups 3, 4, and 5), ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 100%survival (N 鈮?4) after 4 wk. On the other hand, animals from WI only, or WI + SCS groups all died within 24 h of transplantation. Fresh livers preserved using SCS had the highest alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the lowest bile production during reperfusion, while at 28 d post-transplantation, livers preserved at 20掳C and 30掳C had the highest total bilirubin values.

lass="h4">Conclusions

MP at both 20掳C and 30掳C eliminated temperature control in perfusion systems and recovered ischemically damaged rat livers. Postoperatively, low transaminases suggest a beneficial effect of sub-normothermic perfusion, while rising total bilirubin levels suggest inadequate prevention of ischemia- or hypothermia-induced biliary damage.