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Ex vivo liver perfusion

Carolina Rodriguez-Tirado, Takanori Kitamura, Yu Kato, Jeffery W Pollard, John S Condeelis, David Entenberg
Metastasis to secondary sites such as the lung, liver and bone is a traumatic event with a mortality rate of approximately 90% (1). Of these sites, the lung is the most difficult to assess using intravital optical imaging due to its enclosed position within the body, delicate nature and vital role in sustaining proper physiology. While clinical modalities (positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT)) are capable of providing noninvasive images of this tissue, they lack the resolution necessary to visualize the earliest seeding events, with a single pixel consisting of nearly a thousand cells...
October 6, 2016: Journal of Visualized Experiments: JoVE
E Yu, H Ueta, H Kimura, Y Kitazawa, Y Sawanobori, K Matsuno
Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication, with no presently available animal model and no preventive measure. To develop a rat LT-GvHD model, we preconditioned hosts with sublethal irradiation plus reduction of NK cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared to those in the peripheral counterpart, graft CD4(+) CD25(-) passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD4(+) T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs...
October 12, 2016: American Journal of Transplantation
Sheo B Singh, Ling Kang, Andrea R Nawrocki, Dan Zhou, Margaret Wu, Stephen Previs, Corey Miller, Haiying Liu, Catherine D G Hines, Maria Madeira, Jin Cao, Kithsiri Herath, Liangsu Wang, David E Kelley, Cai Li, Hong-Ping Guan
OBJECTIVES: Platensimycin (PTM) is a natural antibiotic produced by Streptomyces platensis that selectively inhibits bacterial and mammalian fatty acid synthase (FAS) without affecting synthesis of other lipids. Recently, we reported that oral administration of PTM in mouse models (db/db and db/+) with high de novo lipogenesis (DNL) tone inhibited DNL and enhanced glucose oxidation, which in turn led to net reduction of liver triglycerides (TG), reduced ambient glucose, and improved insulin sensitivity...
2016: PloS One
Amani Cherif-Sayadi, Kaouther Hadj Ayed-Tka, Mohamed Bejaoui, Neyla Ben Gdara, Mohamed Amine Zaouali, Hassen Ben Abdennebi
BACKGROUND The ability of nitrite to provide protection following ischemia/reperfusion (I/R) has been demonstrated, but its mechanism is still poorly understood. This study aimed to determine the optimal nitrite concentration to add into Institut Georges Lopez (IGL-1) storage solution and to assess its effect on antioxidant enzymes and autophagy. MATERIAL AND METHODS Livers from Sprague-Dawley rats were conserved in IGL-1 for 24 hours at 4°C or in IGL-1 enriched with nitrite at 50, 500 and 1,000 nM, respectively, before being perfused ex-vivo at 37 °C for 120 minutes...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Tiantian Mou, Zuoquan Zhao, Linyi You, Yesen Li, Qian Wang, Wei Fang, Jie Lu, Cheng Peng, Xianzhong Zhang
This study reports three novel (18)F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with (18)F. The total radiosynthesis time of these tracers was 70-90 min. Typical decay-corrected radiochemical yields were 47-58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo...
2016: Scientific Reports
Mariusz Bral, Boris Gala-Lopez, David Bigam, Norman Kneteman, Andrew Malcolm, Scott Livingstone, Axel Andres, Juliet Emamaullee, Leslie Russell, Constantin Coussios, Lori J West, Peter J Friend, A M James Shapiro
After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver UK trial demonstrated feasibility and clear safety, with improved liver function when compared to standard static cold storage (SCS). We herein present a preliminary single centre North-American experience using identical NMP technology. Ten donor liver grafts were procured, 4 (40%) from donation after circulatory death (DCD) donors, of which 9 were transplanted. One liver did not proceed due to a technical failure with portal cannulation, and discarded...
September 17, 2016: 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
INTRODUCTION: Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemic injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of pro-inflammatory cytokines during perfusion. METHODS: Livers retrieved under heart beating conditions were perfused for 4 hours. Following preservation period, pig liver transplantation was performed. In group-1 (n=5) anti-inflammatory strategies (alprostadil, n-acetylcysteine, CO and sevoflurane, subnormothermic temperature (33°C)) were applied...
August 24, 2016: Liver Transplantation
Christina P Keravnou, Ine De Cock, Ine Lentacker, Maria-Louisa Izamis, Michalakis A Averkiou
Localized drug delivery and uptake can benefit from the combined action of ultrasound and microbubbles at a specific site. Some of the possible mechanisms suggested are vessel poration and/or cell poration, but the exact acoustic parameters that trigger those phenomena remain unknown. Ex vivo machine perfusion of human-sized organs is a technique that provides an ideal environment for pre-clinical investigations with high physiologic relevance not possible with in vitro experiments. In this work, ex vivo machine-perfused pig livers were combined with an image-guided therapy system to investigate microvascular flow changes caused by the interaction of ultrasound-driven microbubbles with the vasculature...
November 2016: Ultrasound in Medicine & Biology
Thomas Schreiter, Jan-Peter Sowa, Martin Schlattjan, Jürgen Treckmann, Andreas Paul, Karl-Heinz Strucksberg, Hideo A Baba, Margarete Odenthal, Robert K Gieseler, Guido Gerken, Gavin E Arteel, Ali Canbay
Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period...
2016: Scientific Reports
Toshiaki Kashiwadate, Shigehito Miyagi, Yasuyuki Hara, Yorihiro Akamatsu, Satoshi Sekiguchi, Naoki Kawagishi, Noriaki Ohuchi, Susumu Satomi
Transplantation using grafts obtained after cardiac death (CD) is considered a promising solution for graft shortages. However, no standard criteria for organ preservation have been established for CD donors. High-mobility group box 1 (HMGB1) is a DNA-binding protein that is released from dying hepatocytes as an early mediator of inflammation and organ tissue damage. HMGB1 stimulates immunocytes to produce inflammatory cytokines, thereby amplifying the inflammatory response. Thrombomodulin is an integral membrane protein that functions as an endothelial anticoagulant cofactor, and it binds HMGB1 through the extracellular domain...
2016: Tohoku Journal of Experimental Medicine
Sebastian Pratschke, Hannah Arnold, Alfred Zollner, Michael Heise, Andreas Pascher, Peter Schemmer, Marcus N Scherer, Andreas Bauer, Karl-Walter Jauch, Jens Werner, Markus Guba, Martin K Angele
BACKGROUND: Organ shortage results in the transplantation of extended donor criteria (EDC) livers which is associated with increased ischemia-reperfusion injury (IRI). Experimental studies indicate that an organ rinse with the calcineurin inhibitor tacrolimus before implantation protects against IRI. The tacrolimus organ perfusion study was initiated to examine the effects of ex vivo tacrolimus perfusion on IRI in transplantation of EDC livers. METHODS: A prospective randomized multicenter trial comparing ex vivo perfusion of marginal liver grafts (≥2 EDC according to Eurotransplant manual) with tacrolimus (20 ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out at 5 German liver transplant centers (Munich Ludwig-Maximilians University, Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013...
June 2016: Transplantation Direct
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
Franz G M Poch, Christian Rieder, Hanne Ballhausen, Verena Knappe, Jörg-Peter Ritz, Ole Gemeinhardt, Martin E Kreis, Kai S Lehmann
PURPOSE: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA. MATERIALS AND METHODS: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20 mm, energy input 40 kJ). A saline-perfused glass tube ('vessel') was placed parallel to the applicators in order to simulate a natural liver vessel...
November 2016: International Journal of Hyperthermia
Junxi Xiang, Xinglong Zheng, Peng Liu, Dinghui Dong, Xuemin Liu, Yi Lu
The quality of a donor liver after cardiac death is closely associated with energy metabolism during preservation. Ex vivo mechanical perfusion has broad application prospects because this technique can help energy metabolism and repair ischemia injury of donors' livers. Some core issues are presented in this review in order to provide references for propelling secure application of liver transplantation based on donation after cardiac death.
February 2016: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
C I Øie, K Roepstorff, C Behrens, J Bøggild Kristensen, D M Karpf, G Bolt, C N Gudme, M Kjalke, B Smedsrød, R S Appa
UNLABELLED: Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance. Anatomical and hepatocellular distribution of FVIII is independent of high-affinity VWF binding. ABSTRACT: Background Von Willebrand factor (VWF) stabilizes factor VIII in the circulation and prevents its premature clearance...
September 2016: Journal of Thrombosis and Haemostasis: JTH
Paria Mahboub, Adel Bozorgzadeh, Paulo N Martins
There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications...
June 24, 2016: World 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(TM) , a non-FDA approved bovine derived gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin based Steen solution. METHODS: Transplant outcomes of 10 human liver grafts that were perfused on the Metra(TM) device at 37°C with Steen solution, plus 3 units of erythrocytes were compared to a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique...
June 24, 2016: Liver Transplantation
Kai S Lehmann, Franz G M Poch, Christian Rieder, Andrea Schenk, Andrea Stroux, Bernd B Frericks, Ole Gemeinhardt, Christoph Holmer, Martin E Kreis, Jörg P Ritz, Urte Zurbuchen
BACKGROUND: The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo. METHODS: Glass tubes (vessels) of 3.4 mm inner diameter were introduced in parallel to bipolar RFA applicators into porcine liver ex vivo. Vessels were perfused with flow rates of 0 to 1,500 ml/min. RFA (30 W power, 15 kJ energy input) was carried out at room temperature and 37°C. Heat sink effects were assessed in RFA cross sections by the decrease in ablation radius, area and by a high-resolution sector planimetry...
August 2016: Journal of Hepato-biliary-pancreatic Sciences
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.
June 10, 2016: Annals of Surgery
K J Parker, J Ormachea, S A McAleavey, R W Wood, J J Carroll-Nellenback, R K Miller
The frequency dependent behavior of tissue stiffness and the dispersion of shear waves in tissue can be measured in a number of ways, using integrated imaging systems. The microchannel flow model, which considers the effects of fluid flow in the branching vasculature and microchannels of soft tissues, makes specific predictions about the nature of dispersion. In this paper we introduce a more general form of the 4 parameter equation for stress relaxation based on the microchannel flow model, and then derive the general frequency domain equation for the complex modulus...
July 7, 2016: Physics in Medicine and Biology
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