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Normothermic Ex vivo perfusion

Bhavisha Bakrania, Joey P Granger, Romain Harmancey
The mammalian heart is a major consumer of ATP and requires a constant supply of energy substrates for contraction. Not surprisingly, alterations of myocardial metabolism have been linked to the development of contractile dysfunction and heart failure. Therefore, unraveling the link between metabolism and contraction should shed light on some of the mechanisms governing cardiac adaptation or maladaptation in disease states. The isolated working rat heart preparation can be used to follow, simultaneously and in real time, cardiac contractile function and flux of energy providing substrates into oxidative metabolic pathways...
September 28, 2016: Journal of Visualized Experiments: JoVE
Sarah A Hosgood, Michael L Nicholson
BACKGROUND: The measurement of urinary biomarkers during ex-vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output...
September 27, 2016: Transplantation
J Moritz Kaths, Jun Yu Cen, Yi Min Chun, Juan Echeverri, Ivan Linares, Sujani Ganesh, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A Robinson, Markus Selzner
Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) vs. short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS vs. prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 minutes of warm ischemia, kidneys were removed from 30kg Yorkshire pigs and preserved for 16h with: A) 16h SCS, B) 15h SCS + 1h NEVKP, C) 8h SCS + 8h NEVKP, D) 16h NEVKP...
September 20, 2016: American Journal of Transplantation
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
Ellen F Carney
No abstract text is available yet for this article.
October 2016: Nature Reviews. Nephrology
Christopher White, Emma Ambrose, Alison Müller, Sanaz Hatami, Yun Li, Hoa Le, James Thliveris, Rakesh Arora, Trevor Lee, Ian Dixon, Ganghong Tian, Jayan Nagendran, Larry Hryshko, Darren Freed
BACKGROUND: Hearts donated after circulatory death may represent an additional donor source. The influx of sodium and calcium ions across the sarcolemma play a central role in the pathogenesis of ischemia-reperfusion injury; however, this process may be inhibited if the initial reperfusion solution is rendered hypocalcemic and acidic. We sought to determine the calcium concentration and pH of the initial reperfusion solution that yielded optimal functional recovery of hearts donated after circulatory death during ex vivo heart perfusion...
August 12, 2016: Annals of Thoracic Surgery
Karim Hamaoui, Sally Gowers, Martyn Boutelle, Terry Cook, George Hanna, Ara Darzi, Richard Smith, Anthony Dorling, Vassilios Papalois
BACKGROUND: Hypothermic machine organ perfusion (HMP) offers opportunity to manipulate grafts with pharmacological agents prior to transplantation. Pretreating organs with novel cytotopic anti-coagulant peptides that localise to endothelial cell membranes could ameliorate microvascular thrombotic sequelae posttransplantation. We describe experiments testing Thrombalexin (TLN), a novel cell binding thrombin-inhibitor, using porcine and unused human kidneys in a series of ex-vivo normothermic haemo-reperfusion models...
August 5, 2016: Transplantation
J Moritz Kaths, Juan Echeverri, Nicolas Goldaracena, Kristine S Louis, Yi-Min Chun, Ivan Linares, Aryn Wiebe, Daniel B Foltys, Paul M Yip, Rohan John, Istvan Mucsi, Anand Ghanekar, Darius J Bagli, David R Grant, Lisa A Robinson, Markus Selzner
BACKGROUND: Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation. METHODS: Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation...
September 2016: Transplantation
J Moritz Kaths, Juan Echeverri, Yi Min Chun, Jun Yu Cen, Nicolas Goldaracena, Ivan Linares, Luke S Dingwell, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa Robinson, Markus Selzner
BACKGROUND: Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques such as normothermic perfusion. METHODS: We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation...
July 27, 2016: Transplantation
Pierre Mordant, Daisuke Nakajima, Ricardo Kalaf, Ilker Iskender, Lucas Maahs, Paula Behrens, Rafael Coutinho, Rohin K Iyer, John E Davies, Marcelo Cypel, Mingyao Liu, Thomas K Waddell, Shaf Keshavjee
BACKGROUND: Ex vivo lung perfusion (EVLP) presents a unique therapeutic opportunity to administer mesenchymal stromal cells (MSCs) to lung grafts before transplantation. We sought to determine the optimal route and dose of viable human umbilical cord-derived MSCs to be delivered into ex vivo-perfused damaged swine lungs, and to measure their effect on concentration of growth factors and inflammatory mediators. METHODS: Pig lungs were conventionally retrieved, cold preserved for 18 hours, and perfused normothermically ex vivo for 12 hours...
May 6, 2016: Journal of Heart and Lung 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(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
Xingyu Wang, Yabo Wang, Roumen Parapanov, Etienne Abdelnour, Fabrizio Gronchi, Jean Yannis Perentes, Lise Piquilloud, Hans-Beat Ris, Igor Letovanec, Lucas Liaudet, Thorsten Krueger
BACKGROUND: Donor lungs obtained after prolonged warm ischemia (WI) may be unsuitable for transplantation due to the risk of reperfusion injury, but could be reconditioned using ex-vivo lung perfusion (EVLP). Key processes of reperfusion injury include the formation of reactive oxygen species (ROS)/nitrogen species (RNS) and the activation of poly(adenosine diphosphate-ribose) polymerase (PARP). We explored whether rat lungs obtained after WI could be reconditioned during EVLP using the ROS/RNS scavenger Mn(III)-tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the PARP inhibitor 3-aminobenzamide (3-AB)...
July 2016: 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.
June 10, 2016: Annals of Surgery
S A Hosgood, K Saeb-Parsy, M O Hamed, M L Nicholson
We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in-situ perfusion but subsequently transplanted after perfusion and assessment using ex-vivo normothermic perfusion (EVNP). The kidneys were from a 35y male, donation after circulatory death (DCD) donor. Both kidneys were declined by all UK transplant centres. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation which didn't clear after a further attempt to flush them...
June 7, 2016: American Journal of Transplantation
Mohamed Zeriouh, Anton Sabashnikov, Prashant N Mohite, Bartlomiej Zych, Nikhil P Patil, Diana García-Sáez, Achim Koch, Alexander Weymann, Simona Soresi, Jens Wippermann, Thorsten Wahlers, Fabio De Robertis, Aron-Frederik Popov, André R Simon
OBJECTIVES: Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation...
September 2016: Interactive Cardiovascular and Thoracic Surgery
Virginia Linacre, Marcelo Cypel, Tiago Machuca, Daisuke Nakajima, Kohei Hashimoto, Ricardo Zamel, Manyin Chen, Ilker Iskender, Pedro Dos Santos, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
BACKGROUND: Ex vivo lung perfusion (EVLP) allows for the evaluation and treatment of donor lungs before transplant. Different EVLP strategies have been described using either an open left atrium (LA) (pressure of 0 mm Hg) or closed LA (pressure of 5 mm Hg). We hypothesized that maintaining a physiologic positive LA pressure during EVLP is protective to the lung. METHODS: Pig lungs were flushed with Perfadex, retrieved and stored at 4°C for 4 hours [short cold ischemic time (CIT), n = 10] or 18 hours (prolonged CIT, n = 8)...
June 2016: Journal of Heart and Lung 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
Cissy Yong, Sarah A Hosgood, Michael L Nicholson
PURPOSE OF REVIEW: Marginal donor kidneys make up a substantial proportion of transplanted kidneys. Nonetheless, they are more susceptible to injury during procurement and preservation. Normothermic perfusion is an alternative method of organ preservation that can be used to improve the quality, resuscitate, assess and potentially repair the organ. This review provides an up-to-date summary of the role of normothermic perfusion in renal transplantation and what we can expect in the future...
June 2016: Current Opinion in Organ Transplantation
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