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Subnormothermic ex vivo perfusion

Daniel Urcuyo, Matthew F Blum, Qiang Liu, Ahmed Nassar, Laura D Buccini, Teresa Diago Uso, Emilio D Poggio, William M Baldwin Iii, David A Goldfarb, Cristiano Quintini
PURPOSE: Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. METHODS: 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen)...
June 9, 2017: International Journal of Artificial Organs
J Moritz Kaths, Andreas Paul, Lisa A Robinson, Markus Selzner
Kidney transplantation is the treatment of choice for end-stage renal disease. Despite its superiority over dialysis, the persisting organ shortage remains a major drawback. Additional sources to increase the donor pool are grafts recovered from extended criteria donors (ECD) and donation after circulatory death (DCD). Although transplantation of marginal grafts demonstrates promising outcomes, increased rates of primary non-function, delayed graft function, and reduced graft survival have been reported. Cold ischemic injury, caused by static cold storage is a significant risk factor for poor outcome...
January 2018: Transplantation Reviews
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)...
May 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, 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
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
Vinzent N Spetzler, Nicolas Goldaracena, Juan Echiverri, J Moritz Kaths, Kristine S Louis, Oyedele A Adeyi, Paul M Yip, David R Grant, Nazia Selzner, Markus Selzner
We developed a novel technique of subnormothermic ex vivo liver perfusion (SNEVLP) for the storage of liver grafts before transplantation. To test the safety of SNEVLP for the nonextended criteria grafts (standard grafts), we compared it to a control group with minimal cold static storage (CS) time. Heart-beating pig liver retrieval was performed. Grafts were either stored in cold unmodified University of Wisconsin solution (CS-1), in cold University of Wisconsin solution with ex vivo perfusion additives (CS-2), or preserved with a sequence of 3 hours CS and 3 hours SNEVLP (33°C), followed by orthotopic liver transplantation...
January 2016: Liver Transplantation
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
Samar K Lowalekar, Patrick R Treanor, Hemant S Thatte
OBJECTIVES: Hearts preserved ex vivo at 4 ° C undergo time-dependent irreversible injury due to extreme hypothermia. Studies using novel organ preservative solution SOMAH, suggest that hearts are optimally 'preserved' at subnormothermic temperature of 21 ° C. Present study evaluates relative efficacy of SOMAH 'cardioplegia' at 4 and 21 ° C in preservation of optimum heart function after in vitro storage at subnormothermia. METHODS: Porcine hearts arrested with SOMAH cardioplegia at 4 or 21 ° C were stored in SOMAH for 5-hour at 21 ° C (n = 5)...
2014: Journal of Cardiothoracic Surgery
Jan M Knaak, Vinzent N Spetzler, Nicolas Goldaracena, Markus U Boehnert, Fateh Bazerbachi, Kristine S Louis, Oyedele A Adeyi, Leonid Minkovich, Paul M Yip, Shaf Keshavjee, Gary A Levy, David R Grant, Nazia Selzner, Markus Selzner
An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined...
November 2014: Liver Transplantation
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...
August 13, 2014: Journal of Visualized Experiments: JoVE
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
E Gringeri, M Polacco, F E D'Amico, M Scopelliti, D Bassi, P Bonsignore, R Luisetto, E Lodo, A Carraro, G Zanus, U Cillo
BACKGROUND: Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation. METHODS: Landrace pigs were used in this experiment...
May 2011: Transplantation Proceedings
Herman Tolboom, Maria-Louisa Izamis, Nripen Sharma, Jack M Milwid, Basak Uygun, François Berthiaume, Korkut Uygun, Martin L Yarmush
BACKGROUND: Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37°C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20°C and 30°C. METHODS: Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1) WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20°C, (4) 30°C, and (5) 37°C...
June 1, 2012: Journal of Surgical Research
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