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ex-vivo lung perfusion

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https://www.readbyqxmd.com/read/29312756/history-of-lung-transplantation
#1
REVIEW
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
https://www.readbyqxmd.com/read/29298188/sphingosine-kinase-1-regulates-inflammation-and-contributes-to-acute-lung-injury-in-pneumococcal-pneumonia-via-the-sphingosine-1-phosphate-receptor-2
#2
Birgitt Gutbier, Stefanie M Schönrock, Carolin Ehrler, Rainer Haberberger, Kristina Dietert, Achim D Gruber, Wolfgang Kummer, Laura Michalick, Wolfgang M Kuebler, Andreas C Hocke, Kolja Szymanski, Eleftheria Letsiou, Anja Lüth, Fabian Schumacher, Burkhard Kleuser, Timothy J Mitchell, Wilhelm Bertrams, Bernd Schmeck, Denise Treue, Frederick Klauschen, Torsten T Bauer, Mario Tönnies, Norbert Weissmann, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath
OBJECTIVES: Severe pneumonia may evoke acute lung injury, and sphingosine-1-phosphate is involved in the regulation of vascular permeability and immune responses. However, the role of sphingosine-1-phosphate and the sphingosine-1-phosphate producing sphingosine kinase 1 in pneumonia remains elusive. We examined the role of the sphingosine-1-phosphate system in regulating pulmonary vascular barrier function in bacterial pneumonia. DESIGN: Controlled, in vitro, ex vivo, and in vivo laboratory study...
January 2, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29295855/the-%C3%AE-2-agonist-terbutaline-specifically-decreases-pulmonary-arterial-pressure-under-normoxia-and-hypoxia-via-%C3%AE-adrenoceptor-antagonism
#3
Vanessa Neumann, Ralf Knies, Alexander Seidinger, Annika Simon, Kristina Lorenz, Michaela Matthey, Johannes Breuer, Daniela Wenzel
Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29240608/metabolic-profile-of-ex-vivo-lung-perfusate-yields-biomarkers-for-lung-transplant-outcomes
#4
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
https://www.readbyqxmd.com/read/29191716/pulmonary-absorption-estimation-of-effective-pulmonary-permeability-and-tissue-retention-of-ten-drugs-using-an-ex-vivo-rat-model-and-computational-analysis
#5
Johanna Eriksson, Erik Sjögren, Helena Thörn, Katarina Rubin, Per Bäckman, Hans Lennernäs
Permeation of inhaled drugs across the pulmonary epithelium can regulate the rate and extent of local drug absorption and hence the pulmonary tissue concentration. Therefore, understanding pulmonary epithelial transport could be important for successful design of novel inhaled medicines. To enhance understanding of pulmonary epithelial transport, drug transport data were generated for a set of inhaled compounds (n=10) in the single-pass, isolated perfused rat lung model. A compartmental in silico model was used to estimate pulmonary permeability and tissue retention...
November 27, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29153638/%C3%AE-1-anti-trypsin-improves-function-of-porcine-donor-lungs-during-ex-vivo-lung-perfusion
#6
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
https://www.readbyqxmd.com/read/29140963/when-the-momentum-has-gone-what-will-be-the-role-of-extracorporeal-lung-support-in-the-future
#7
Darryl Abrams, Matthew Bacchetta, Daniel Brodie
PURPOSE OF REVIEW: There has been expanding interest in and use of extracorporeal support in respiratory failure concurrent with technological advances and predominantly observational data demonstrating improved outcomes. However, until there is more available data from rigorous, high-quality randomized studies, the future of extracorporeal support remains uncertain. RECENT FINDINGS: Outcomes for patients supported with extracorporeal devices continue to show favorable trends...
February 2018: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/29128023/evaluation-and-management-of-the-potential-lung-donor
#8
REVIEW
Andrew Courtwright, Edward Cantu
The expansion of the donor lung pool has involved an evidence-driven redefinition of acceptable donors. Proceeding with transplantation with an acceptable rather than ideal donor depends on specific patient-related and organ-related risk factors as well as the severity of recipient illness. Although the physiologic optimization of brain-dead donors has not changed significantly in recent years, the use of donor management protocols has improved procurement rates. Ex vivo lung perfusion is an increasingly viable strategy to recondition lungs that would otherwise fall below the acceptable threshold for transplant...
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29110788/worldwide-trends-in-heart-and-lung-transplantation-guarding-the-most-precious-gift-ever
#9
REVIEW
Vera von Dossow, Joseph Costa, Frank D'Ovidio, Nandor Marczin
Transplantation is sadly a therapy to die for. The survival of a recipient with end-stage heart or lung disease requires the demise of a human being through brain death or cessation of circulation, with the noblest final act of offering one's organs to another. However, transplantation is constrained by severe hemodynamic, regulatory, inflammatory, and metabolic stresses in the donor, rendering the majority of offered organs unsuitable for transplantation. Coupled with our inability to acquire exact molecular and cellular information and missed opportunities for effectively modulating deteriorations of donors and allografts, anesthesia and critical care contributes to ongoing organ shortages...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/29109929/opportunities-for-therapeutic-intervention-during-machine-perfusion
#10
Negin Karimian, Heidi Yeh
Purpose of review: There is a vast discrepancy between the number of patients waiting for organ transplantation and the available donor organs. Ex vivo machine perfusion (MP) has emerged in an effort to expand the donor pool, by improving organ preservation, providing diagnostic information, and more recently, acting as a platform for organ improvement. This article reviews the current status of MP with a focus on its role in organ preconditioning and therapeutic interventions prior to transplantation...
June 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29103845/negative-pressure-ventilation-decreases-inflammation-and-lung-edema-during-normothermic-ex-vivo-lung-perfusion
#11
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
https://www.readbyqxmd.com/read/29102342/bioengineered-lungs-a-challenge-and-an-opportunity
#12
Ramon Farré, Jordi Otero, Isaac Almendros, Daniel Navajas
Lung biofabrication is a new tissue engineering and regenerative development aimed at providing organs for potential use in transplantation. Lung biofabrication is based on seeding cells into an acellular organ scaffold and on culturing them in an especial purpose bioreactor. The acellular lung scaffold is obtained by decellularizing a non-transplantable donor lung by means of conventional procedures based on application of physical, enzymatic and detergent agents. To avoid immune recipient's rejection of the transplanted bioengineered lung, autologous bone marrow/adipose tissue-derived mesenchymal stem cells, lung progenitor cells or induced pluripotent stem cells are used for biofabricating the bioengineered lung...
November 1, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29089091/-ex-becomes-in-a-new-direction-for-ex%C3%A2-vivo-lung-perfusion
#13
EDITORIAL
John H Dark
No abstract text is available yet for this article.
September 30, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28985871/ex%C3%A2-vivo-treatment-with-inhaled-n-acetylcysteine-in-porcine-lung-transplantation
#14
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
https://www.readbyqxmd.com/read/28964417/continued-successful-evolution-of-extended-criteria-donor-lungs-for-transplantation
#15
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
https://www.readbyqxmd.com/read/28948134/contemporary-issues-in-lung-transplant-allocation-practices
#16
Wayne M Tsuang
PURPOSE OF REVIEW: To discuss the current state of donor lung allocation in the United States, and future opportunities to increase the efficiency of donor lung allocation. RECENT FINDINGS: The current donor lung allocation system prioritizes clinical acuity by use of the Lung Allocation Score (LAS) which has reduced waitlist mortality since its implementation in 2005. Access to donor lungs can be further improved through policy changes using broader geographic sharing, and developing new technology such as ex vivo lung perfusion to recover marginal donor lungs...
September 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/28945476/assessment-of-lungs-for-transplant-recovered-from-uncontrolled-donation-after-circulatory-determination-of-death-donors
#17
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
https://www.readbyqxmd.com/read/28945469/pharmacologic-protection-of-mitochondrial-dna-integrity-may-afford-a-new-strategy-for-suppressing-lung-ischemia-reperfusion-injury
#18
Yong B Tan, Sujata Mulekar, Olena Gorodnya, Michael J Weyant, Martin R Zamora, Jon D Simmons, Tiago Machuka, Mark N Gillespie
Lung ischemia-reperfusion (IR) injury contributes to post-transplant complications, including primary graft dysfunction. Decades of reports show that reactive oxygen species generated during lung IR contribute to pulmonary vascular endothelial barrier disruption and edema formation, but the specific target molecule(s) that "sense" injury-inducing oxidant stress to activate signaling pathways culminating in pathophysiologic changes have not been established. This review discusses evidence that mitochondrial DNA (mtDNA) may serve as a molecular sentinel wherein oxidative mtDNA damage functions as an upstream trigger for lung IR injury...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28936437/ex-vivo-lung-perfusion-review-of-a-revolutionary-technology
#19
REVIEW
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
https://www.readbyqxmd.com/read/28924829/a-comparison-of-drug-transport-in-pulmonary-absorption-models-isolated-perfused-rat-lungs-respiratory-epithelial-cell-lines-and-primary-cell-culture
#20
Cynthia Bosquillon, Michaela Madlova, Nilesh Patel, Nicola Clear, Ben Forbes
PURPOSE: To evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo. METHOD: The permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo...
September 18, 2017: Pharmaceutical Research
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