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Normothermic Ex vivo liver perfusion

Federica Rigo, Nicola De Stefano, Victor Navarro-Tableros, Ezio David, Giorgia Rizza, Giorgia Catalano, Nicholas Gilbo, Francesca Maione, Federica Gonella, Dorotea Roggio, Silvia Martini, Damiano Patrono, Mauro Salizzoni, Giovanni Camussi, Renato Romagnoli
BACKGROUND: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS: We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution...
February 9, 2018: Transplantation
Juan Echeverri, Nicolas Goldaracena, Johan Moritz Kaths, Ivan Linares, Roizar Roizales, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Sujani Ganesh, Oyedele A Adeyi, Mahmood Tazari, Markus Selzner, Nazia Selzner
BACKGROUND: The optimal vasodilator to avoid hepatic artery (HA) vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), Epoprostenol (prostacyclin analogue), and Verapamil (calcium channel antagonist). METHODS: Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: Group 1: livers perfused with a dose of 1...
November 20, 2017: Transplantation
Xiaoshun He, Fei Ji, Zhiheng Zhang, Yunhua Tang, Lu Yang, Shanzhou Huang, Wenwen Li, Qiao Su, Wei Xiong, Zebin Zhu, Linhe Wang, Lei Lv, Jiyou Yao, Linan Zhang, Longjuan Zhang, Zhiyong Guo
It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C)...
January 2018: Liver Transplantation
F Baroncelli, M C Alberione, V Cacciotti, D Artusio, M Vergano, S Livigni
A 20-minute hands-off period with isoelectric electrocardiography (ECG) monitoring is currently required for the declaration of cardiac death in Italy, thus prolonging the warm ischemia time (WIT) during donation after circulatory death (DCD). Normothermic regional perfusion (NRP) can be a valid tool to optimize organ perfusion as a bridge to donation. A 62-year-old woman with catastrophic brain injury due to massive intracranial hemorrage, not fulfilling brain death criteria, underwent controlled DCD after withdrawal of life-sustaining therapies (WLST)...
May 2017: Transplantation Proceedings
Hazel Marecki, Adel Bozorgzadeh, Robert J Porte, Henri G Leuvenink, Korkut Uygun, Paulo N Martins
Ex vivo machine perfusion (MP) is a promising way to better preserve livers prior to transplantation. Currently, no methodology has a verified benefit over simple cold storage. Before becoming clinically feasible, MP requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, whose physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored MP as preservation, but only recently have clinical trials been performed...
May 2017: Liver Transplantation
Shanice A Karangwa, Laura C Burlage, Jelle Adelmeijer, Negin Karimian, Andrie C Westerkamp, Alix P Matton, Rianne van Rijn, Janneke Wiersema-Buist, Micheal E Sutton, Sanna Op den Dries, Ton Lisman, Robert J Porte
BACKGROUND: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability before transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo. METHODS: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid. Concentration of prothrombin fragment F1 + 2 (marker of coagulation activation), D-dimer, plasmin-antiplasmin complex, tissue plasminogen activator and plasminogen activator inhibitor-1 (markers for fibrinolysis) and alanine aminotransferase (ALT) (marker of ischemia-reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals...
February 2017: Transplantation
N Goldaracena, V N Spetzler, J Echeverri, J M Kaths, V Cherepanov, R Persson, M R Hodges, H L A Janssen, N Selzner, D R Grant, J J Feld, M Selzner
Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS)...
April 2017: American Journal of Transplantation
Mihai-Calin Pavel, Constantino Fondevila Campo, Victor Molina Santos, Alba Diaz Lorca, Juan Carlos Garcia-Valdecasas Salgado
No abstract text is available yet for this article.
May 2017: Cirugía Española
M Bral, B Gala-Lopez, D Bigam, N Kneteman, A Malcolm, S Livingstone, A Andres, J Emamaullee, L Russell, C Coussios, L J West, P J Friend, A M J Shapiro
After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single-center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded...
April 2017: American Journal of Transplantation
Nicolas Goldaracena, Juan Echeverri, Vinzent N Spetzler, Johan M Kaths, Andrew S Barbas, Kristine S Louis, Oyedele A Adeyi, David R Grant, Nazia Selzner, Markus Selzner
Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied...
November 2016: Liver Transplantation
A S Barbas, S J Knechtle
In this issue of the American Journal of Transplantation, Mergental and colleagues from Birmingham, UK report the successful transplantation of five discarded liver allografts following an evaluation period by normothermic ex-vivo liver perfusion (NEVLP) (1). They applied a combination of objective (perfusate lactate/pH, bile production This article is protected by copyright. All rights reserved.
July 12, 2016: American Journal of Transplantation
Markus Selzner, Nicolas Goldaracena, Juan Echeverri, Johan M Kaths, Ivan Linares, Nazia Selzner, Cyril Serrick, Max Marquez, Gonzalo Sapisochin, Eberhard L Renner, Mamatha Bhat, Ian D McGilvray, Leslie Lilly, Paul D Greig, Cynthia Tsien, Mark S Cattral, Anand Ghanekar, David R Grant
The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique...
November 2016: Liver Transplantation
Christopher J E Watson, Lucy V Randle, Vasilis Kosmoliaptsis, Paul Gibbs, Michael Allison, Andrew J Butler
No abstract text is available yet for this article.
January 2017: Annals of Surgery
A S Barbas, N Goldaracena, M J Dib, M Selzner
Liver transplantation is the optimal treatment for end-stage liver disease but is limited by the severe shortage of donor organs. This shortage has prompted increased utilization of marginal grafts from DCD and extended criteria donors, which poorly tolerate cold storage in comparison to standard criteria grafts. Ex-vivo liver perfusion (EVLP) technology has emerged as a potential alternative to cold storage for organ preservation, but there is no consensus regarding the optimal temperature or conditions for EVLP...
July 2016: Transplantation Reviews
Nicolas Goldaracena, Andrew S Barbas, Markus Selzner
PURPOSE OF REVIEW: In the current era of extreme organ shortage, warm (subnormothermic and normothermic) ex-vivo liver perfusion has emerged as a novel strategy to recover marginal organs and increase the organ pool. Over the last decade, significant progress in the field has taken this technology from bench to bedside. This review will cover the most relevant contributions to the field in 2015. RECENT FINDINGS: Several groups made significant advances in warm ex-vivo liver perfusion for optimizing preservation of liver grafts...
June 2016: Current Opinion in Organ Transplantation
Ahmed Nassar, Qiang Liu, Kevin Farias, Laura Buccini, William Baldwin, Ana Bennett, Martin Mangino, Samuel Irefin, Jacek Cywinski, Toshihiro Okamoto, Teresa Diago Uso, Giuseppe Iuppa, Basem Soliman, Charles Miller, Cristiano Quintini
Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group)...
October 2016: Artificial Organs
Laurens J Ceulemans, Sébastien Strypstein, Arne Neyrinck, Stijn Verleden, David Ruttens, Diethard Monbaliu, Paul De Leyn, Johan Vanhaecke, Bart Meyns, Frederik Nevens, Geert Verleden, Dirk Van Raemdonck, Jacques Pirenne
Combined liver/thoracic transplantation (cLiThTx) is a complex procedure for end-stage/advanced liver and heart(H)/lung(Lu) disease. To avoid futile use of multiple organs in single recipients, results should be scrutinously analyzed. Single-center cLiThTx (04/2000-12/2015) were reviewed for the following: demographics, indications, surgical technique, complications, rejection, and five-year patient survival. Results are reported as median (range). Fourteen consecutive patients underwent cLiThTx: 3 cLiHTx, 10 cLiLuTx, and 1 cLiHLuTx...
June 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Babak Banan, Rao Watson, Min Xu, Yiing Lin, William Chapman
Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers...
July 2016: Liver Transplantation
Sanna Op den Dries, Negin Karimian, Andrie C Westerkamp, Michael E Sutton, Michiel Kuipers, Janneke Wiersema-Buist, Petra J Ottens, Jeroen Kuipers, Ben N Giepmans, Henri G D Leuvenink, Ton Lisman, Robert J Porte
Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion...
July 2016: Liver Transplantation
Radhika Chadha, Mohammad Ayaz Hossain, Atul Bagul
No abstract text is available yet for this article.
2016: Expert Review of Medical Devices
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