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Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Takeshi Kondo, Hideki Motoyama, Akihiro Ohsumi, Daisuke Nakajima, Jin Sakamoto, Keiji Ohata, Mamoru Takahashi, Satona Tanaka, Ei Miyamoto, Akihiro Aoyama, Hiroshi Date
BACKGROUND: We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with high-dose short-acting β2-adrenergic receptor agonists. METHODS: Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 μg of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP...
October 10, 2016: Annals of Thoracic Surgery
Toshihiro Okamoto, David Wheeler, Qiang Liu, Cristiano Quintini, J Steven Hata, Kenneth R McCurry
BACKGROUND: Ex vivo lung perfusion (EVLP) may be an essential process for the pre-transplant evaluation of the donor lungs. Currently, the partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, or PF) ratio is the standard in the assessment of lung function in cellular EVLP, whereas other parameters, including airway and vascular parameters, have only been partially utilized. The primary purpose of this study is to assess the potential utility of other parameters as a surrogate of lung function in EVLP...
May 20, 2016: Journal of Heart and Lung Transplantation
Eric J Charles, Mary E Huerter, Cynthia E Wagner, Ashish K Sharma, Yunge Zhao, Mark H Stoler, J Hunter Mehaffey, James M Isbell, Christine L Lau, Curtis G Tribble, Victor E Laubach, Irving L Kron
BACKGROUND: Despite the critical need for donor lungs, logistic and geographic barriers hinder lung utilization. We hypothesized that lungs donated after circulatory death subjected to 6 hours of cold preservation after ex vivo lung perfusion (EVLP) would have similar outcomes after transplantation as lungs transplanted immediately after EVLP, and that both would perform superiorly compared with lungs transplanted immediately after procurement. METHODS: Donor porcine lungs were procured after circulatory death and 15 minutes of warm ischemia...
September 7, 2016: Annals of Thoracic Surgery
Lisa H Cazares, Michael D Ward, Ernst E Brueggemann, Tara Kenny, Paul Demond, Christopher R Mahone, Karen A O Martins, Jonathan E Nuss, Trevor Glaros, Sina Bavari
BACKGROUND: Ebola virus like particles (EBOV VLPs, eVLPs), are produced by expressing the viral transmembrane glycoprotein (GP) and structural matrix protein VP40 in mammalian cells. When expressed, these proteins self-assemble and bud from 'host' cells displaying morphology similar to infectious virions. Several studies have shown that rodents and non-human primates vaccinated with eVLPs are protected from lethal EBOV challenge. The mucin-like domain of envelope glycoprotein GP1 serves as the major target for a productive humoral immune response...
2016: Clinical Proteomics
An Martens, Marc Boada, Bart M Vanaudenaerde, Stijn E Verleden, Robin Vos, Geert M Verleden, Eric K Verbeken, Dirk Van Raemdonck, Dominique Schols, Sandra Claes, Arne P Neyrinck
Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex-vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm-ischemic injury in a porcine model (n=6/group). Following cardiac arrest, grafts were left untouched in the donor (90 minutes warm ischemia). Graft function was assessed after 6 hours of EVLP. In MP-group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP...
August 12, 2016: Transplant International: Official Journal of the European Society for Organ 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
Andreas Wallinder, Gerdt C Riise, Sven-Erik Ricksten, Martin Silverborn, Göran Dellgren
BACKGROUND: A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. METHODS: Single-center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period...
May 31, 2016: Journal of Heart and Lung 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
Pablo G Sanchez, Kristen M Mackowick, Zachary N Kon
PURPOSE OF REVIEW: The purpose of the current report is to review the ex-vivo peer-reviewed literature published in the last 5 years and to summarize the findings. RECENT FINDINGS: Encouraging data have been published by several centers utilizing ex-vivo lung perfusion (EVLP) as a means to identify viable grafts from the high-risk donor pool. The outcomes of transplanted lungs that were initially declined because of poor quality, but reevaluated with ex-vivo perfusion, are equivalent to standard criteria donor lungs...
June 2016: Current Opinion in Organ Transplantation
Luis Gustavo Abdalla, Karina Andrighetti de Oliveira Braga, Natalia Aparecida Nepomuceno, Lucas Matos Fernandes, Marcos Naoyuki Samano, Paulo Manuel Pêgo-Fernandes
OBJECTIVE: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. METHODS: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated...
April 2016: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
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
Marcelo Cypel, Shaf Keshavjee
PURPOSE OF REVIEW: The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. A novel strategy of donor lung management, ex-vivo lung perfusion (EVLP), that keeps the organ at physiological protective conditions has shown great promise to increase lung utilization by re-evaluating, treating, and repairing donor lungs prior to transplantation...
June 2016: Current Opinion in Organ Transplantation
Mary E Huerter, Ashish K Sharma, Yunge Zhao, Eric J Charles, Irving L Kron, Victor E Laubach
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major source of morbidity and mortality after lung transplantation. We previously demonstrated a proinflammatory role of adenosine A2B receptor (A2BR) in lung IR injury. The current study tests the hypothesis that A2BR antagonism is protective of ischemic lungs after in vivo reperfusion or ex vivo lung perfusion (EVLP). METHODS: Mice underwent lung IR with or without administration of ATL802, a selective A2BR antagonist...
August 2016: Annals of Thoracic Surgery
Nhung T Huynh, Emma L Hesketh, Pooja Saxena, Yulia Meshcheriakova, You-Chan Ku, Linh T Hoang, John E Johnson, Neil A Ranson, George P Lomonossoff, Vijay S Reddy
Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C terminus of the small (S) subunit...
April 5, 2016: Structure
An Martens, Matteo Montoli, Giulio Faggi, Ira Katz, Jan Pype, Bart M Vanaudenaerde, Dirk E M Van Raemdonck, Arne P Neyrinck
BACKGROUND: Evidence supports the use of ex vivo lung perfusion (EVLP) as a platform for active reconditioning before transplantation to increase the potential donor pool and to reduce the incidence of primary graft dysfunction. A promising reconditioning strategy is the administration of inhaled noble gases based on their organoprotective effects. Our aim was to validate a porcine warm ischemic lung injury model and investigate postconditioning with argon (Ar) or xenon (Xe) during prolonged EVLP...
March 2016: Journal of Surgical Research
Raphaël Briot, Stéphane Gennai, Maxime Maignan, Redha Souilamas, Christophe Pison
This review proposes an update of the state of the art and the ongoing clinical trials of ex vivo lung perfusion for lung transplantation in patients. Ex vivo lung perfusion techniques (EVLP) can be used to evaluate a lung graft outside of the body. The goal of EVLP is to study the functional status of lung grafts that were first rejected for transplantation because they did not match all criteria for a conventional transplantation. After an EVLP evaluation, some of these lungs may be requalified for a possible transplantation in patients...
April 2016: Anaesthesia, Critical Care & Pain Medicine
D Nakajima, M Cypel, R Bonato, T N Machuca, I Iskender, K Hashimoto, V Linacre, M Chen, R Coutinho, S Azad, T Martinu, T K Waddell, D M Hwang, S Husain, M Liu, S Keshavjee
Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics...
April 2016: American Journal of Transplantation
Michiel E Erasmus, Dirk van Raemdonck, Mohammed Zeeshan Akhtar, Arne Neyrinck, David Gomez de Antonio, Andreas Varela, John Dark
In an era where there is a shortage of lungs for transplantation is increased utilization of lungs from donation after circulatory death (DCD) donors. We review the reports of 11 controlled and 1 uncontrolled DCD programs focusing on donor criteria, procedural criteria, graft assessment, and preservation techniques including the use of ex vivo lung perfusion. We have formulated conclusions and recommendations for each of these areas, which were presented at the 6th International Conference on Organ Donation...
July 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Jessica G Y Luc, Jayan Nagendran
Despite the rise in the number of adult lung transplantations performed, rates of pediatric lung transplantation remain low. Lung transplantation is an accepted therapy for pediatric end-stage lung disease; however, it is limited by a shortage of donor organs. EVLP has emerged as a platform for assessment and preservation of donor lung function. EVLP has been adopted in adult lung transplantation and has successfully led to increased adult lung transplantations and donor lung utilization. We discuss the future implications of EVLP utilization, specifically, its potential evolving role in overcoming donor shortages in smaller children and adolescents to improve the quality and outcomes of lung transplantation in pediatric patients...
February 2016: Pediatric Transplantation
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