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Subnormothermic machine perfusion

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
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
Thomas Minor, Katja Sutschet, Oliver Witzke, Andreas Paul, Anja Gallinat
BACKGROUND: Post-transplant function of suboptimal kidney grafts can be improved but not accurately predicted by hypothermic machine perfusion. Therefore, a new concept of ex situ pre-implantation machine perfusion with controlled rewarming up to subnormothermic temperatures was developed and evaluated. MATERIALS AND METHODS: Porcine kidneys (n = 6/group) were retrieved before or 30 min after cardiac arrest of the donor and subjected to 18 h of static cold storage...
December 2016: European Journal of Clinical Investigation
Anna Cleta Croce, Andrea Ferrigno, Vittorio Bertone, Valeria Maria Piccolini, Clarissa Berardo, Laura Giuseppina Di Pasqua, Vittoria Rizzo, Giovanni Bottiroli, Mariapia Vairetti
AIM: Livers with moderate steatosis are currently recruited as marginal organs to face donor shortage in transplantation, despite lipid excess and oxidative stress increase preservation injury risk. A sensitive, real time detection of liver metabolism engagement could help donor selection and preservation procedures, ameliorating the graft outcome. Hence, we investigated endogenous biomolecules with autofluorescence (AF) properties as biomarkers supporting the detection of liver oxidative events and the assessment of metabolic responses to external stimuli...
July 23, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
M Furukori, N Matsuno, L T Meng, T Shonaka, Y Nishikawa, K Imai, H Obara, H Furukawa
BACKGROUND: The use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, the implementation of such a strategy requires the development of novel preservation methods to recover from changes owing to warm ischemia. The aim of this study was to evaluate the effectiveness of subnormothermic machine perfusion (MP) preservation with rewarming for porcine DCD liver grafts for transplantation. METHODS: Porcine livers were perfused with newly developed MP system...
May 2016: Transplantation Proceedings
M Hagiwara, N Matsuno, L T Meng, M Furukori, K Watanabe, T Shonaka, K Imai, H Obara, Y Nishikawa, H Furukawa
BACKGROUND: The use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. The objective of this study is to determine the benefits of extracorporeal membrane oxygenation (ECMO) and subnormothermic machine perfusion (MP) with rewarming in a large animal model of DCD liver. METHODS: After cardiac arrest, the abdominal aorta and the inferior vena cava were cannulated and connected to an ECMO circuit. Porcine livers were perfused in situ with ECMO at 22°C for 60 minutes after 60 minutes of cardiac death...
May 2016: Transplantation Proceedings
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
Bote G Bruinsma, Gautham V Sridharan, Pepijn D Weeder, James H Avruch, Nima Saeidi, Sinan Özer, Sharon Geerts, Robert J Porte, Michal Heger, Thomas M van Gulik, Paulo N Martins, James F Markmann, Heidi Yeh, Korkut Uygun
As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion...
March 3, 2016: Scientific Reports
Andrie C Westerkamp, Paria Mahboub, Sophie L Meyer, Maximilia Hottenrott, Petra J Ottens, Janneke Wiersema-Buist, Annette S H Gouw, Ton Lisman, Henri G D Leuvenink, Robert J Porte
A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions...
October 2015: Liver Transplantation
Ina Schopp, Elmo Reissberg, Bastian Lüer, Patrik Efferz, Thomas Minor
Early graft dysfunction due to preservation/reperfusion injury still represents a notable issue after kidney transplantation, affecting long term prognosis of graft viability. One trigger of postischemic cell dysfunction could be recognized in the abrupt temperature shift from hypo- to normothermia, leading to mitochondrial dysfunction and proapoptotic signal transduction. Here we propose a technique to cope with this "rewarming injury" by interposing a period of gentle warming up by hypo- to subnormothermic machine perfusion of the isolated graft prior to warm reperfusion...
October 2015: Clinical and Translational Science
Bote G Bruinsma, James H Avruch, Pepijn D Weeder, Gautham V Sridharan, Basak E Uygun, Negin G Karimian, Robert J Porte, James F Markmann, Heidi Yeh, Korkut Uygun
There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic machine perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels...
2015: Journal of Visualized Experiments: JoVE
Bote G Bruinsma, Tim A Berendsen, Maria-Louisa Izamis, Heidi Yeh, Martin L Yarmush, Korkut Uygun
The current standard for liver preservation involves cooling of the organ on ice (0-4 °C). Although it is successful for shorter durations, this method of preservation does not allow long-term storage of the liver. The gradual loss of hepatic viability during preservation puts pressure on organ sharing and allocation, may limit the use of suboptimal grafts and necessitates rushed transplantation to achieve desirable post-transplantation outcomes. In an attempt to improve and prolong liver viability during storage, alternative preservation methods are under investigation...
March 2015: Nature Protocols
Jun-Jun Jia, Jian-Hui Li, Li Jiang, Bin-Yi Lin, Li Wang, Rong Su, Lin Zhou, Shu-Sen Zheng
BACKGROUND: Liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver protection. DATA SOURCES: Databases such as PubMed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words: "ischemia reperfusion injury", "graft preservation", "liver transplantation", "machine perfusion" and "conditioning"...
February 2015: Hepatobiliary & Pancreatic Diseases International: HBPD INT
P Fontes, R Lopez, A van der Plaats, Y Vodovotz, M Minervini, V Scott, K Soltys, S Shiva, S Paranjpe, D Sadowsky, D Barclay, R Zamora, D Stolz, A Demetris, G Michalopoulos, J W Marsh
We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions(21 °C) with a new hemoglobin-based oxygen carrier (HBOC) solution. MP (n=6) was compared to cold static preservation (CSP; n=6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5-day follow-up. Recipients' peripheral blood, serial liver biopsies, preservation solutions and bile specimens were collected before, during and after liver preservation. Clinical laboratorial and histological analyses were performed in addition to mitochondrial functional assays, transcriptomic, metabolomic and inflammatory inflammatory mediator analyses...
February 2015: American Journal of Transplantation
E Tarantola, V Bertone, G Milanesi, C Gruppi, A Ferrigno, M Vairetti, S Barni, I Freitas
Graft steatosis is a risk factor for poor initial function after liver transplantation. Biliary complications are frequent even after normal liver transplantation. A subnormothermic machine perfusion (MP20) preservation procedure was developed by our group with high potential for reducing injury to hepatocytes and sinusoidal cells of lean and fatty livers respect to conventional cold storage (CS). We report the response of the biliary tree to CS or MP20, in lean and obese Zucker rat liver. Dipeptidylpeptidase-IV (DPP-IV), crucial for the inactivation of incretins and neuropeptides, was used as a marker...
2014: European Journal of Histochemistry: EJH
Jan M Knaak, Vinzent N Spetzler, Nicolas Goldaracena, Kristine S Louis, Nazia Selzner, Markus Selzner
The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for liver transplantation die without receiving an organ transplant or are delisted for disease progression. One strategy to increase the donor pool is the utilization of marginal grafts, such as fatty livers, grafts from older donors, or donation after cardiac death (DCD). The current preservation technique of cold static storage is only poorly tolerated by marginal livers resulting in significant organ damage...
2014: Journal of Visualized Experiments: JoVE
Dieter P Hoyer, Anja Gallinat, Sandra Swoboda, Jeremias Wohlschläger, Ursula Rauen, Andreas Paul, Thomas Minor
Machine perfusion for preservation led to compelling success for the outcome of renal transplantation. Further refinements of methods to decrease preservation injury remain an issue of high interest. This study investigates functional and morphological aspects of kidneys preserved by subnormothermic (20 °C) machine perfusion (SNTM) compared with oxygenated hypothermic machine perfusion (HMPox) and cold storage (CS) in a donation after circulatory death (DCD) model. After 30 min of warm ischaemia, porcine kidneys were randomly assigned to preservation for 7 h by CS, HMPox or SNTM...
October 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
N Matsuno, K Uchida, H Furukawa
Because of the critical shortage of deceased donor grafts, using a donation after cardiac death (DCD) donor is an important resource. However, the ischemic damage of those DCD grafts jeopardizes organ viability during cold storage. Maintaining organ viability after donation until transplantation is important for optimal graft function and survival. This review describes the effective preservation in transplantation for DCD livers. Concepts and development of machine perfusion for DCD liver grafts to reduce ischemia/reperfusion injury are discussed...
May 2014: Transplantation Proceedings
Jay A Graham, James V Guarrera
As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex vivo techniques such as hypothermic, normothermic, and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury...
August 2014: Journal of Hepatology
B G Bruinsma, H Yeh, S Ozer, P N Martins, A Farmer, W Wu, N Saeidi, S Op den Dries, T A Berendsen, R N Smith, J F Markmann, R J Porte, M L Yarmush, K Uygun, M-L Izamis
To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic machine perfusion (21°C) on seven livers discarded for transplantation...
June 2014: American Journal of Transplantation
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