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Norman Zinne, Marcus Krueger, Doris Hoeltig, Burkhard Tuemmler, Erin C Boyle, Christian Biancosino, Klaus Hoeffler, Peter Braubach, Taufiek K Rajab, Anatol Ciubotaru, Judith Rohde, Karl-Heinz Waldmann, Axel Haverich
The emergence of multi-drug resistant bacteria threatens to end the era of antibiotics. Drug resistant bacteria have evolved mechanisms to overcome antibiotics at therapeutic doses and further dose increases are not possible due to systemic toxicity. Here we present a pilot study of ex vivo lung perfusion (EVLP) with high dose antibiotic therapy followed by autotransplantation as a new therapy of last resort for otherwise incurable multidrug resistant lung infections. Severe Pseudomonas aeruginosa pneumonia was induced in the lower left lungs (LLL) of 18 Mini-Lewe pigs...
2018: PloS One
Jonathan C Yeung, Ricardo Zamel, William Klement, Xiao-Hui Bai, Tiago N Machuca, Thomas K Waddell, Mingyao Liu, Marcelo Cypel, Shaf Keshavjee
We and others have demonstrated that acellular normothermic ex vivo lung perfusion of high-risk donor lungs can result in post-transplant outcomes equivalent to that of contemporaneous lung transplantation using standard donor lungs. However, the mechanism of this effect remains unclear. Given the restoration of cellular metabolic activity during normothermic perfusion, one possibility is that of lung healing via natural innate recovery mechanisms. We explored this by examining the gene expression changes occurring in human lungs during ex vivo lung perfusion...
February 15, 2018: American Journal of Transplantation
Xingyu Wang, Roumen Parapanov, Cyril Francioli, Jean Yannis Perentes, Igor Letovanec, Michel Gonzalez, Christian Kern, Hans-Beat Ris, Lise Piquilloud, Carlo Marcucci, Thorsten Krueger, Lucas Liaudet, Fabrizio Gronchi
OBJECTIVES: Volatile anaesthetics can provide significant protection against reperfusion injury in various experimental settings. The aim of this study was to assess the potential of sevoflurane treatment, the most commonly used volatile anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death and reconditioned in an ex vivo lung perfusion (EVLP) system. METHODS: Fifteen rats were sacrificed and divided into 3 groups. In the control and sevoflurane groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in the presence of 2% sevoflurane...
January 24, 2018: Interactive Cardiovascular and Thoracic Surgery
Federico Venuta, Dirk Van Raemdonck
Lung transplantation nowadays is a well-accepted and routine treatment for well selected patients with terminal respiratory disease. However, it took several decades of experimental studies and clinical attempts to reach this success. In this paper, we describe the early experimental activity from the mid-forties until the early sixties. The first clinical attempt in humans was reported by Hardy and Webb in 1963 followed by others with short survival only except for one case by Derom et al. who lived for 10 months...
December 2017: Journal of Thoracic Disease
Michael K Hsin, Ricardo Zamel, Marcelo Cypel, David Wishart, Beomsoo Han, Shaf Keshavjee, Mingyao Liu
OBJECTIVE: To identify potential biomarkers during ex vivo lung perfusion (EVLP) using metabolomics approach. SUMMARY BACKGROUND DATA: EVLP increases the number of usable donor lungs for lung transplantation (LTx) by physiologic assessment of explanted marginal lungs. The underlying paradigm of EVLP is the normothermic perfusion of cadaveric lungs previously flushed and stored in hypothermic preservation fluid, which allows the resumption of active cellular metabolism and respiratory function...
January 2018: Annals of Surgery
Alberto Berardi, David J Evans, Francesca Baldelli Bombelli, George P Lomonossoff
Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical (i.e. digestion of the polypeptides) stability of CPMV and its empty virus-like particles (eVLPs) in conditions resembling the gastrointestinal fluids were evaluated...
January 25, 2018: Nanoscale
Huiqing Lin, Manyin Chen, Feng Tian, Jussi Tikkanen, Lei Ding, Hei Yu Andrew Cheung, Daisuke Nakajima, Zhe Wang, Andrea Mariscal, David Hwang, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu
BACKGROUND: Ex-vivo lung perfusion (EVLP), a technique for donor lung assessment, also represents a platform for donor lung repair and immunomodulation. α1 -Anti-trypsin (A1AT), a medication used to treat emphysema in A1AT-deficient patients, has anti-inflammatory properties and has been shown to attenuate ischemia-reperfusion injury in rat and pig lung transplants. The objective of this study was to determine whether administration of A1AT during EVLP can improve donor lung quality after prolonged hypothermic preservation...
October 2, 2017: Journal of Heart and Lung Transplantation
Nader S Aboelnazar, Sayed Himmat, Sanaz Hatami, Christopher W White, Mohamad S Burhani, Peter Dromparis, Nobutoshi Matsumura, Ganghong Tian, Jason R B Dyck, Michael Mengel, Darren H Freed, Jayan Nagendran
BACKGROUND: Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. METHODS: Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC)...
September 14, 2017: Journal of Heart and Lung Transplantation
Yulia Meshcheriakova, Alex Durrant, Emma L Hesketh, Neil A Ranson, George P Lomonossoff
Particles of cowpea mosaic virus (CPMV) have enjoyed considerable success as nanoparticles. The development of a system for producing empty virus-like particles (eVLPs) of the virus, which are non-infectious and have the potential to be loaded with heterologous material, has increased the number of possible applications for CPMV-based particles. However, for this potential to be realised, it was essential to demonstrate that eVLPs were accurate surrogates for natural virus particles, and this information was provided by high-resolution cryo-EM studies of eVLPs...
November 3, 2017: Biochemical Society Transactions
Yoshito Yamada, Ilker Iskender, Stephan Arni, Sven Hillinger, Tugba Cosgun, Keke Yu, Wolfgang Jungraithmayr, Nikola Cesarovic, Walter Weder, Ilhan Inci
BACKGROUND: We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. METHODS: Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6)...
October 2017: Journal of Surgical Research
Sakhee Kotecha, Jamie Hobson, Jeremy Fuller, Eldho Paul, Bronwyn J Levvey, Helen Whitford, Miranda Paraskeva, David McGiffin, Gregory I Snell, Glen P Westall
BACKGROUND: In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation. METHODS: Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second)...
November 2017: Annals of Thoracic Surgery
Thomas Egan, John Blackwell, Katherine Birchard, Benjamin Haithcock, Jason Long, Stephen Gazda, Nissa Casey, Caitlin Thys
RATIONALE: To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). OBJECTIVES: To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. METHODS: After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan...
September 2017: Annals of the American Thoracic Society
George Makdisi, Tony Makdisi, Tambi Jarmi, Christiano C Caldeira
Donor lung shortage has been the main reason to the increasing number of patients waiting for lung transplant. Ex vivo lung perfusion (EVLP) is widely expanding technology to assess and prepare the lungs who are considered marginal for transplantation. the outcomes are encouraging and comparable to the lungs transplanted according to the standard criteria. in this article, we will discuss the history of development, the techniques and protocols of ex vivo, and the logics and rationales for ex vivo use.
September 2017: Annals of Translational Medicine
J G Y Luc, K Jackson, J G Weinkauf, D H Freed, J Nagendran
BACKGROUND: Donation after circulatory death (DCD) has the potential to significantly alleviate the shortage of transplantable lungs. We report our initial experience with the use of portable ex vivo lung perfusion (EVLP) with the Organ Care System Lung device for evaluation of DCD lungs. METHODS: We performed a retrospective review of the DCD lung transplantation (LTx) experience at a single institution through the use of a prospective database. RESULTS: From 2011 to 2015, 208 LTx were performed at the University of Alberta, of which 11 were DCD LTx with 7 (64%) that underwent portable EVLP...
October 2017: Transplantation Proceedings
Tugba Cosgun, Ilker Iskender, Yoshito Yamada, Stephan Arni, Miriam Lipiski, Koen van Tilburg, Walter Weder, Ilhan Inci
OBJECTIVES: Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. METHODS: Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each)...
July 1, 2017: European Journal of Cardio-thoracic Surgery
Hannah C D'Cunha, Mauricio Rojas
Lung transplant is the only therapy for several end-stage lung diseases; however, the number of donated lungs suitable for transplant is not sufficient, and hundreds of patients have died waiting for an organ. Ex vivo lung perfusion (EVLP) has emerged as a new technology with the potential of reconditioning human donor lungs previously unsuitable for transplantation. Since the first successful transplant of a lung treated using EVLP in the year 2000, multiple clinical trials have demonstrated, in several transplant centers around the word, the feasibility and the potential of EVLP to increase the total number of lungs available for transplant...
August 29, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Ilja V Khavrutskii, Sidhartha Chaudhury, Sabrina M Stronsky, Donald W Lee, Jacqueline G Benko, Anders Wallqvist, Sina Bavari, Christopher L Cooper
Recent advances in the next-generation sequencing of B-cell receptors (BCRs) enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 10(3)-10(5) sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them...
2017: Frontiers in Immunology
Annika Liersch-Nordqvist, Mohammed Fakhro, Leif Pierre, Joanna Hlebowicz, Malin Malmsjo, Richard Ingemansson, Sandra Lindstedt
OBJECTIVE: Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function...
October 2017: Annals of Medicine and Surgery
A Venkataraman, J W Blackwell, W K Funkhouser, K R Birchard, S E Beamer, W T Simmons, S H Randell, T M Egan
BACKGROUND: We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. CASE REPORT: A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported...
September 2017: Transplantation Proceedings
Tobias Nilsson, Jan F Gielis, Alexis Slama, Christoffer Hansson, Andreas Wallinder, Sven-Erik Ricksten, Göran Dellgren
BACKGROUND: Two clinically used strategies for ex vivo lung perfusion (EVLP) were compared in a porcine model with respect to lung function, metabolism, inflammatory response, oxidative stress, and cell viability. METHODS: Porcine lungs (n = 20) were preserved, harvested, and kept cooled for 2 hours. After randomization, EVLP was performed using a cellular perfusate and open left atrium (COA group) or an acellular perfusate and a closed left atrium (ACA group). Oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen), compliance, dead space, weight, and perfusate oncotic pressure were registered before and after a 4-hour period of reconditioning...
July 8, 2017: Journal of Heart and Lung Transplantation
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