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Ex vivo liver perfusion

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https://www.readbyqxmd.com/read/28733731/novel-laparoscopic-training-system-with-continuously-perfused-ex-vivo-porcine-liver-for-hepatobiliary-surgery
#1
Wenyan Liu, Xinglong Zheng, Rongqian Wu, Yinbin Jin, Shu Kong, Jianpeng Li, Jianwen Lu, Huan Yang, Xianghua Xu, Yi Lv, Xiaogang Zhang
OBJECTIVE: To introduce a novel laparoscopic training system with a continuously perfused ex-vivo porcine liver for hepatobiliary surgery. BACKGROUND: Existing models for laparoscopic training, such as box trainers and virtual reality simulators, often fail to provide holistic training and real haptic feedback. We have formulated a new training system that addresses these problems. METHODS: Real-Liver Laptrainer consists of a porcine liver, customized mannequin, ex-vivo machine perfusion system, and monitoring software...
July 21, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28694661/relevance-of-proteolysis-and-proteasome-activation-in-fatty-liver-graft-preservation-an-institut-georges-lopez-1-vs-university-of-wisconsin-appraisal
#2
Mohamed Amine Zaouali, Arnau Panisello-Roselló, Alexandre Lopez, Carlos Castro Benítez, Emma Folch-Puy, Agustín García-Gil, Teresa Carbonell, René Adam, Joan Roselló-Catafau
AIM: To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions. METHODS: Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to "ex vivo" normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28637520/citrulline-decreases-hepatic-endotoxin-induced-injury-in-fructose-induced-non-alcoholic-liver-disease-an-ex-vivo-study-in-the-isolated-perfused-rat-liver
#3
Wassila Ouelaa, Prasanthi Jegatheesan, Japhète M'bouyou-Boungou, Christelle Vicente, Samir Nakib, Esther Nubret, Jean-Pascal De Bandt
Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats...
June 22, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28557337/a-reappraisal-of-the-proposed-metabolic-and-antioxidant-actions-of-butylated-hydroxytoluene-bht-in-the-liver
#4
Lorena Dos Santos Castro, Lívia Bracht, Jurandir Fernando Comar, Rosane Marina Peralta, Adelar Bracht
Butylated hydroxytoluene (BHT) was investigated for its metabolic actions in the perfused rat liver. Contrary to what is expected from an uncoupler, BHT up to 500 μM did not stimulate oxygen uptake nor did it inhibit gluconeogenesis from lactate. Transformation of fructose into glucose was also not affected by BHT; only lactate production was slightly increased at the concentration of 100 μM. The uncoupling effect of BHT in isolated mitochondria was confirmed, but only at concentrations above 10 μM; uncoupling at lower concentrations, 10(-9) to 10(-6)  M, could not be confirmed...
May 29, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#5
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28463671/urgent-organ-retrieval-from-non-heart-beating-donor-with-declared-brain-death-harvest-at-arrest
#6
Ihsan Yıldız, Yavuz Savaş Koca, Mehmet Zafer Sabuncuoglu
OBJECTIVE: Due to insufficient donor number to meet the needs of organ transplantation, new researches are ongoing. In this context, the cases with cardiac arrest and brain dead are assessed as probable donors in recent years. The aim of this study is to discuss the healthfully techniques of organs retrieval with minimum damage and maximum rapidity in conditions of our center and to present our own experiences. MATERIAL AND METHOD: A total 4 of 13 patients brain dead declared and developed cardiac arrest while awaiting for laboratory test results in our center between 2015 and 2016, were urgently taken into operation under external heart massage and urgent organ retrieval were performed...
March 2017: Chirurgia
https://www.readbyqxmd.com/read/28457385/blood-lactate-concentrations-before-and-after-withdrawal-of-life-sustaining-treatments-in-controlled-donation-after-circulatory-death-a-case-report-from-italy
#7
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
https://www.readbyqxmd.com/read/28421681/early-clinical-xenotransplantation-experiences-an-interview-with-thomas-e-starzl-md-phd
#8
REVIEW
David K C Cooper
Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of organ transplantation. He was also a pioneer in the field of xenotransplantation. In 1964, he carried out baboon kidney transplants in six patients with terminal renal disease for whom no living or deceased donor became available; graft survival was for 19-60 days, the grafts being lost largely through continuous complement activation. Between 1966 and 1974, he carried out one ex vivo liver perfusion and three orthotopic liver transplants using chimpanzees as sources of organs; graft survival was for <14 days...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28364696/differential-effects-of-liver-steatosis-on-pharmacokinetic-profile-of-two-closely-related-hepatoselective-no-donors-v-pyrro-no-and-v-proli-no
#9
Kamil Kus, Edyta Kus, Agnieszka Zakrzewska, Wojciech Jawien, Barbara Sitek, Maria Walczak, Stefan Chlopicki
PURPOSE: To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. METHODS: C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28357909/nitrite-enhances-liver-graft-protection-against-cold-ischemia-reperfusion-injury-through-a-nos-independent-pathway
#10
Amani Cherif-Sayadi, Kaouther Hadj Ayed-Tka, Mohamed Amine Zaouali, Mohamed Bejaoui, Najet Hadj-Abdallah, Ahlem Bouhlel, Hassen Ben Abdennebi
INTRODUCTION: Nitrite has been found to protect liver graft from cold preservation injury. However, the cell signaling pathway involved in this protection remains unclear. Here, we attempt to clarify if the NOS pathway by using the NOS inhibitor, L-NAME (L-N(G)-Nitroarginine methyl ester). ANIMALS AND METHODS: Rat livers were conserved for 24 h at 4°C in (IGL-1) solution enriched or not with nitrite at 50 nM. In a third group, rats were pretreated with 50 mg/kg of L-NAME before their liver procurement and preservation in IGL-1 supplemented with nitrite (50 nM) and L-NAME (1 mM)...
December 2017: Libyan Journal of Medicine
https://www.readbyqxmd.com/read/28266040/ex-vivo-porcine-organ-perfusion-models-as-a-suitable-platform-for-translational-transplant-research
#11
Rohan Kumar, Wen Yuan Chung, Ashley Robert Dennison, Giuseppe Garcea
In transplantation surgery, extending the criteria for organ donation to include organs that may have otherwise been previously discarded has provided the impetus to improve organ preservation. The traditional method of cold static storage (CS) has been tried and tested and is suitable for organs meeting standard criteria donation. Ex vivo machine perfusion is, however, associated with evidence suggesting that it may be better than CS alone and may allow for organ donation criteria to be extended. Much of our knowledge of organ preservation is derived from animal studies...
March 6, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28241986/short-fasting-does-not-protect-perfused-ex%C3%A2-vivo-rat-liver-against-ischemia-reperfusion-on-the-importance-of-a-minimal-cell-energy-charge
#12
Bérengère Papegay, Michaela Stadler, Vincent Nuyens, Véronique Kruys, Jean G Boogaerts, Joseph Vamecq
OBJECTIVE: Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. METHODS: Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate...
March 2017: Nutrition
https://www.readbyqxmd.com/read/28240817/liver-ex-situ-machine-perfusion-preservation-a-review-of-the-methodology-and-results-of-large-animal-studies-and-clinical-trials
#13
REVIEW
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
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#14
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/27992805/selective-ex%C3%A2-vivo-photothermal-nano-therapy-of-solid-liver-tumors-mediated-by-albumin-conjugated-gold-nanoparticles
#15
Lucian Mocan, Cristian Matea, Flaviu A Tabaran, Ofelia Mosteanu, Teodora Pop, Cosmin Puia, Lucia Agoston-Coldea, Gabriela Zaharie, Teodora Mocan, Anca Dana Buzoianu, Cornel Iancu
We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/27957815/evolution-of-graft-morphology-and-function-after-recellularization-of-decellularized-rat-livers
#16
Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, Benjamin Struecker
Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited. We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n = 21) with primary rat hepatocytes (150 x 10(6) cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1 h, 6 h, 12 h, 24 h, 3d, 5d and 7d after recellularization (all n = 3) by immuno-histologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate...
December 13, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27941437/activation-of-fibrinolysis-but-not-coagulation-during-end-ischemic-ex-situ-normothermic-machine-perfusion-of-human-donor-livers
#17
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
https://www.readbyqxmd.com/read/27867357/machine-perfusion-of-porcine-livers-with-oxygen-carrying-solution-results-in-reprogramming-of-dynamic-inflammation-networks
#18
David Sadowsky, Ruben Zamora, Derek Barclay, Jinling Yin, Paulo Fontes, Yoram Vodovotz
Background:Ex vivo machine perfusion (MP) can better preserve organs for transplantation. We have recently reported on the first application of an MP protocol in which liver allografts were fully oxygenated, under dual pressures and subnormothermic conditions, with a new hemoglobin-based oxygen carrier (HBOC) solution specifically developed for ex vivo utilization. In those studies, MP improved organ function post-operatively and reduced inflammation in porcine livers. Herein, we sought to refine our knowledge regarding the impact of MP by defining dynamic networks of inflammation in both tissue and perfusate...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27860296/impact-of-subnormothermic-machine-perfusion-preservation-in-severely-steatotic-rat-livers-a-detailed-assessment-in-an-isolated-setting
#19
Y Okamura, K Hata, H Tanaka, H Hirao, T Kubota, O Inamoto, S Kageyama, I Tamaki, N Yermek, J Yoshikawa, S Uemoto
The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS)...
November 10, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27805597/study-of-viral-vectors-in-a-three-dimensional-liver-model-repopulated-with-the-human-hepatocellular-carcinoma-cell-line-hepg2
#20
Thomas Hiller, Viola Röhrs, Eva-Maria Dehne, Anke Wagner, Henry Fechner, Roland Lauster, Jens Kurreck
This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals. Another advantage is the humanized nature of the model, which is closer to human physiology than animal models...
October 24, 2016: Journal of Visualized Experiments: JoVE
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