Normothermic Acellular Ex Vivo Liver Perfusion Reduces Liver and Bile Duct Injury of Pig Livers Retrieved After Cardiac Death

被引:111
作者
Boehnert, M. U. [1 ]
Yeung, J. C. [2 ]
Bazerbachi, F. [1 ]
Knaak, J. M. [1 ]
Selzner, N. [3 ]
McGilvray, I. D. [1 ]
Rotstein, O. D. [4 ]
Adeyi, O. A. [5 ]
Kandel, S. M. [6 ]
Rogalla, P. [6 ]
Yip, P. M. [7 ]
Levy, G. A. [3 ]
Keshavjee, S. [2 ]
Grant, D. R. [1 ]
Selzner, M. [1 ]
机构
[1] Toronto Gen Hosp, Multi Organ Transplant Program, Dept Surg, Toronto, ON, Canada
[2] Univ Toronto, Toronto Lung Transplant Program, Toronto, ON, Canada
[3] Toronto Gen Hosp, Dept Med, Multi Organ Transplant Program, Toronto, ON M5G 1L7, Canada
[4] St Michaelss Hosp, Dept Surg, Toronto, ON, Canada
[5] Toronto Gen Hosp, Dept Pathol, Multi Organ Transplant Program, Toronto, ON, Canada
[6] Toronto Gen Hosp, Dept Radiol, Multi Organ Transplant Program, Toronto, ON M5G 2C4, Canada
[7] Toronto Gen Hosp, Dept Lab Med & Pathobiol, Multi Organ Transplant Program, Toronto, ON, Canada
关键词
Biliary complication; preservation; preservation temperature; preservation-reperfusion injury; HYPOTHERMIC MACHINE PRESERVATION; ISCHEMIA-REPERFUSION; HEPATIC STEATOSIS; COLD-STORAGE; DONOR LIVERS; TRANSPLANTATION; DONATION; ALLOGRAFTS; APOPTOSIS; OUTCOMES;
D O I
10.1111/ajt.12224
中图分类号
R61 [外科手术学];
学科分类号
摘要
We compared cold static with acellular normothermic ex vivo liver perfusion (NEVLP) as a novel preservation technique in a pig model of DCD liver injury. DCD livers (60min warm ischemia) were cold stored for 4h, or treated with 4h cold storage plus 8h NEVLP. First, the livers were reperfused with diluted blood as a model of transplantation. Liver injury was determined by ALT, oxygen extraction, histology, bile content analysis and hepatic artery (HA) angiography. Second, AST levels and bile production were assessed after DCD liver transplantation. Cold stored versus NEVLP grafts had higher ALT levels (350 +/- 125 vs. 55 +/- 35U/L; p<0.0001), decreased oxygen extraction (250 +/- 65mmHg vs. 410 +/- 58mmHg, p<0.01) and increased hepatocyte necrosis (45% vs. 10%, p=0.01). Levels of bilirubin, phospholipids and bile salts were fivefold decreased, while LDH was sixfold higher in cold stored versus NEVLP grafts. HA perfusion was decreased (twofold), and bile duct necrosis was increased (100% vs. 5%, p<0.0001) in cold stored versus NEVLP livers. Following transplantation, mean serum AST level was higher in the cold stored versus NEVLP group (1809 +/- 205U/L vs. 524 +/- 187U/L, p<0.05), with similar bile production (2.5 +/- 1.2cc/h vs. 2.8 +/- 1.4cc/h; p=0.2). NEVLP improved HA perfusion and decreased markers of liver duct injury in DCD grafts.
引用
收藏
页码:1441 / 1449
页数:9
相关论文
共 30 条
[1]   Normothermic Perfusion A New Paradigm for Organ Preservation [J].
Brockmann, Jens ;
Reddy, Srikanth ;
Coussios, Constantin ;
Pigott, David ;
Guirriero, Dino ;
Hughes, David ;
Morovat, Alireza ;
Roy, Debabrata ;
Winter, Lucy ;
Friend, Peter J. .
ANNALS OF SURGERY, 2009, 250 (01) :1-6
[2]   Successful extracorporeal porcine liver perfusion for 72 hr [J].
Butler, AJ ;
Rees, MA ;
Wight, DGD ;
Casey, ND ;
Alexander, G ;
White, DJG ;
Friend, PJ .
TRANSPLANTATION, 2002, 73 (08) :1212-1218
[3]   Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation [J].
Cypel, M. ;
Rubacha, M. ;
Yeung, J. ;
Hirayama, S. ;
Torbicki, K. ;
Madonik, M. ;
Fischer, S. ;
Hwang, D. ;
Pierre, A. ;
Waddell, T. K. ;
de Perrot, M. ;
Liu, M. ;
Keshavjee, S. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 (10) :2262-2269
[4]   Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation [J].
Cypel, Marcelo ;
Yeung, Jonathan C. ;
Liu, Mingyao ;
Anraku, Masaki ;
Chen, Fengshi ;
Karolak, Wojtek ;
Sato, Masaaki ;
Laratta, Jane ;
Azad, Sassan ;
Madonik, Mindy ;
Chow, Chung-Wai ;
Chaparro, Cecilia ;
Hutcheon, Michael ;
Singer, Lianne G. ;
Slutsky, Arthur S. ;
Yasufuku, Kazuhiro ;
de Perrot, Marc ;
Pierre, Andrew F. ;
Waddell, Thomas K. ;
Keshavjee, Shaf .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (15) :1431-1440
[5]   Functional Repair of Human Donor Lungs by IL-10 Gene Therapy [J].
Cypel, Marcelo ;
Liu, Mingyao ;
Rubacha, Matt ;
Yeung, Jonathan C. ;
Hirayama, Shin ;
Anraku, Masaki ;
Sato, Masaaki ;
Medin, Jeffrey ;
Davidson, Beverly L. ;
de Perrot, Marc ;
Waddell, Thomas K. ;
Slutsky, Arthur S. ;
Keshavjee, Shaf .
SCIENCE TRANSLATIONAL MEDICINE, 2009, 1 (04)
[6]   Initial Experience With Lung Donation After Cardiocirculatory Death in Canada [J].
Cypel, Marcelo ;
Sato, Masaaki ;
Yildirim, Erkan ;
Karolak, Wojtek ;
Chen, Fengshi ;
Yeung, Jonathan ;
Boasquevisque, Carlos ;
Leist, Victoria ;
Singer, Lianne G. ;
Yasufuku, Kazuhiro ;
DePerrot, Marc ;
Waddell, Thomas K. ;
Keshavjee, Shaf ;
Pierre, Andrew .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2009, 28 (08) :753-758
[7]   Technique for Prolonged Normothermic Ex Vivo Lung Perfusion [J].
Cypel, Marcelo ;
Yeung, Jonathan C. ;
Hirayama, Shin ;
Rubacha, Matthew ;
Fischer, Stefan ;
Anraku, Masaki ;
Sato, Masaaki ;
Harwood, Stephen ;
Pierre, Andrew ;
Waddell, Thomas K. ;
de Perrot, Marc ;
Liu, Mingyao ;
Keshavjee, Shaf .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2008, 27 (12) :1319-1325
[8]   One Hour Hypothermic Oxygenated Perfusion (HOPE) Protects Nonviable Liver Allografts Donated After Cardiac Death [J].
de Rougemont, Olivier ;
Breitenstein, Stefan ;
Leskosek, Boris ;
Weber, Achim ;
Graf, Rolf ;
Clavien, Pierre-Alain ;
Dutkowski, Philipp .
ANNALS OF SURGERY, 2009, 250 (05) :674-683
[9]   Liver Transplantation Using Controlled Donation After Cardiac Death Donors: An Analysis of a Large Single-Center Experience [J].
Grewal, Hani P. ;
Willingham, Darrin L. ;
Nguyen, Justin ;
Hewitt, Winston R. ;
Taner, Bucin C. ;
Cornell, Danielle ;
Rosser, Barry G. ;
Keaveny, Andrew P. ;
Aranda-Michel, Jamie ;
Satyanarayana, Raj ;
Harnois, Denise ;
Dickson, Rolland C. ;
Kramer, David J. ;
Hughes, Christopher B. .
LIVER TRANSPLANTATION, 2009, 15 (09) :1028-1035
[10]   Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series [J].
Guarrera, J. V. ;
Henry, S. D. ;
Samstein, B. ;
Odeh-Ramadan, R. ;
Kinkhabwala, M. ;
Goldstein, M. J. ;
Ratner, L. E. ;
Renz, J. F. ;
Lee, H. T. ;
Brown, R. S., Jr. ;
Emond, J. C. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2010, 10 (02) :372-381