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Ex vivo lung perfusion

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https://www.readbyqxmd.com/read/29740711/new-avenues-for-nanoparticle-related-therapies
#1
Michael Zhao, Mingyao Liu
Development of nanoparticle-based drug delivery systems has been attempted for the treatment of cancer over the past decade. The enhanced permeability and retention (EPR) effect is the major mechanism to passively deliver nanodrugs to tumor tissue. However, a recent systematic review demonstrated limited success of these studies, with the clearance of nanoparticles by the mononuclear phagocytic system (MPS) being a major hurdle. Herein, we propose that nanotechnologists should reconsider their research focuses, aiming for therapeutic targets other than cancer...
May 8, 2018: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29718705/influence-of-ex-vivo-perfusion-on-the-biomolecular-profile-of-rat-lungs
#2
Caterina Lonati, Giulia A Bassani, Daniela Brambilla, Patrizia Leonardi, Andrea Carlin, Alice Faversani, Stefano Gatti, Franco Valenza
Despite increasing clinical adoption, biologic influences of ex vivo lung perfusion (EVLP) remain insufficiently elucidated. The aim of the current study was to investigate biomolecular changes induced by EVLP in rat lungs. EVLP was maintained for 180 min. Hyaluronan, mediators, and cells were assessed in the perfusate. Gene expression, signaling pathways, and ATP content were investigated in lung tissue. EVLP induced the release of medium-high molecular weight hyaluronan and transcription of hyaluronan synthases ( P < 0...
May 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29692722/the-deletion-of-endothelial-sodium-channel-%C3%AE-%C3%AE-enac-impairs-endothelium-dependent-vasodilation-and-endothelial-barrier-integrity-in-endotoxemia-in-vivo
#3
Magdalena Sternak, Anna Bar, Mateusz G Adamski, Tasnim Mohaissen, Brygida Marczyk, Anna Kieronska, Marta Stojak, Kamil Kus, Antoine Tarjus, Frederic Jaisser, Stefan Chlopicki
The role of epithelial sodium channel (ENaC) activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice) using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa , 10 mg/kg, i...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29609890/increasing-circulating-sphingosine-1-phosphate-attenuates-lung-injury-during-ex-vivo-lung-perfusion
#4
J Hunter Mehaffey, Eric J Charles, Adishesh K Narahari, Sarah Schubert, Victor E Laubach, Nicholas R Teman, Kevin R Lynch, Irving L Kron, Ashish K Sharma
BACKGROUND: Sphingosine-1-phosphate regulates endothelial barrier integrity and promotes cell survival and proliferation. We hypothesized that upregulation of sphingosine-1-phosphate during ex vivo lung perfusion would attenuate acute lung injury and improve graft function. METHODS: C57BL/6 mice (n = 4-8/group) were euthanized, followed by 1 hour of warm ischemia and 1 hour of cold preservation in a model of donation after cardiac death. Subsequently, mice underwent 1 hour of ex vivo lung perfusion with 1 of 4 different perfusion solutions: Steen solution (Steen, control arm), Steen with added sphingosine-1-phosphate (Steen + sphingosine-1-phosphate), Steen plus a selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or Steen plus both additives (Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor)...
March 11, 2018: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29605030/effect-of-hypertonic-saline-in-the-pretreatment-of-lung-donors-with-hemorrhagic-shock
#5
Natalia Aparecida Nepomuceno, Karina Andrighetti de Oliveira-Braga, Liliane Moreira Ruiz, Aristides Tadeu Correia, Eduardo Zinoni Silva Pato, Luiz Fernando da Silva, Paulo Manuel Pêgo-Fernandes, Marcos Naoyuki Samano
BACKGROUND: Hemorrhagic shock-induced lung edema and inflammation are two of the main reasons for the rejection of lungs donated for transplantation. Hypertonic saline (HS) induces intravascular volume expansion and has considerable immunomodulating effects that might minimize edema. Our hypothesis is based on the use of a hypertonic solution for treatment of donors who are in shock in an attempt to increase the supply of lungs for transplantation. METHODS: A total of 80 rats were allocated to four groups: one group was given an infusion of normal saline (NS; n = 20), one group received HS; n = 20, a sham group (n = 20), and a Shock group (n = 20)...
May 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29590671/primary-graft-dysfunction-pgd-following-lung-transplantation
#6
Rupal J Shah, Joshua M Diamond
Primary graft dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung allograft dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics...
April 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29579767/donation-after-brain-death-versus-donation-after-circulatory-death-lung-donor-management-issues
#7
Gregory I Snell, Bronwyn J Levvey, Kovi Levin, Miranda Paraskeva, Glen Westall
Lung transplantation (LTx) has traditionally been limited by a lack of suitable donor lungs. With the recognition that lungs are more robust than initially thought, the size of the donor pool of available lungs has increased dramatically in the past decade. Donation after brain death (DBD) and donation after circulatory death (DCD) lungs, both ideal and extended are now routinely utilized. DBD lungs can be damaged. There are important differences in the public's understanding, legal and consent processes, intensive care unit strategies, lung pathophysiology, logistics, and potential-to-actual donor conversion rates between DBD and DCD...
April 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29519557/acute-pancreatitis-conditioned-mesenteric-lymph-causes-cardiac-dysfunction-in-rats-independent-of-hypotension
#8
Satyanarayan T Shanbhag, Bernard Choong, Maxim Petrov, Brett Delahunt, John A Windsor, Anthony R J Phillips
BACKGROUND: Critical illness including severe acute pancreatitis is associated with the multiple organ dysfunction syndrome. The "gut-lymph" hypothesis states that multiple organ dysfunction syndrome is due to release of toxic factors from the intestine into the mesenteric lymph. The aims of this study were to determine the effect of normotensive acute pancreatitis conditioned mesenteric lymph on cardiac function and whether external drainage of mesenteric lymph would protect the heart...
May 2018: Surgery
https://www.readbyqxmd.com/read/29505574/treatment-of-infected-lungs-by-ex-vivo-perfusion-with-high-dose-antibiotics-and-autotransplantation-a-pilot-study-in-pigs
#9
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
https://www.readbyqxmd.com/read/29462333/high-positive-end-expiratory-pressure-during-ex-vivo-lung-perfusion-recruiting-rejected-donor-lungs
#10
Kamal S Ayyat, Toshihiro Okamoto, Hiromichi Niikawa, Kenneth R McCurry
We present an innovative method for recruiting clinically rejected donor lungs using positive end-expiratory pressure titration during ex vivo lung perfusion. Currently, ex vivo lung perfusion protocols are using a standard positive end-expiratory pressure of 5 cmH2O for all cases. Individualized positive end-expiratory pressure titration combined with recruitment manoeuvres has been found to significantly improve pulmonary functions in mechanically ventilated patients. Applying this concept to ex vivo lung perfusion may be helpful in increasing the conversion rate for transplant suitability...
February 14, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29446226/towards-donor-lung-recovery-gene-expression-changes-during-ex-vivo-lung-perfusion-of-human-lungs
#11
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 posttransplant 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
https://www.readbyqxmd.com/read/29427404/interleukin-8-mediates-neutrophil-endothelial-interactions-in-pig-to-human-xenogeneic-models
#12
Beth M French, Selin Sendil, Krishna Mohan Sepuru, Jolene Ranek, Lars Burdorf, Donald Harris, Emily Redding, Xiangfei Cheng, Christopher T Laird, Yuming Zhao, Benjamin Cerel, Krishna Rajarathnam, Richard N Pierson, Agnes M Azimzadeh
BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29412228/the-protective-effect-of-dexmedetomidine-in-a-rat-ex-vivo-lung-model-of-ischemia-reperfusion-injury
#13
Yan Zhou, Xinqiao Zhou, Wenjuan Zhou, Qingfeng Pang, Zhiping Wang
PURPOSE: To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. METHODS: An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio...
January 2018: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29389820/conquering-combined-thoracic-organ-and-liver-transplantation-indications-and-outcomes-for-heart-liver-and-lung-liver-transplantation
#14
Stephanie G Yi, Keri E Lunsford, Courtenay Bruce, R Mark Ghobrial
PURPOSE OF REVIEW: Combined thoracic organ and liver transplantation has been shown to be a viable treatment option for patients with end-stage disease lung or heart and disease. There are increasing number of cases reported in the literature, as the number of institutions utilizing this strategy is growing. Herein, we review the current literature of combined thoracic and liver transplantation. RECENT FINDINGS: A larger number of combined heart or lung and liver transplants (CHLT and CLLT) are being performed...
April 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29376452/devices-for-ex-vivo-heart-and-lung-perfusion
#15
Dean P Schraufnagel, Robert J Steffen, Patrick R Vargo, Tamer Attia, Haytham Elgharably, Saad M Hasan, Alejandro Bribriesco, Per Wierup
The number of organs available for heart and lung transplantation is far short of the number that is needed to meet demand. Perfusion and ventilation of donor organs after procurement has led to exciting advances in the field of cardiothoracic transplantation. The clinical implications of this technology allows for techniques to evaluate the quality of an organ, active rehabilitation of organs after procurement and prior to implantation, and increased time between organ procurement and implantation. This ex-vivo perfusion technique has also been referred to in the lay press as the 'heart in a box' or 'lung in a box...
March 2018: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/29373667/experimental-ex-vivo-lung-perfusion-with-sevoflurane-effects-on-damaged-donor-lung-grafts
#16
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
https://www.readbyqxmd.com/read/29367464/cell-free-hemoglobin-promotes-primary-graft-dysfunction-through-oxidative-lung-endothelial-injury
#17
Ciara M Shaver, Nancy Wickersham, J Brennan McNeil, Hiromasa Nagata, Adam Miller, Stuart R Landstreet, Jamie L Kuck, Joshua M Diamond, David J Lederer, Steven M Kawut, Scott M Palmer, Keith M Wille, Ann Weinacker, Vibha N Lama, Maria M Crespo, Jonathan B Orens, Pali D Shah, Chadi A Hage, Edward Cantu, Mary K Porteous, Gundeep Dhillon, John McDyer, Julie A Bastarache, Jason D Christie, Lorraine B Ware
Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing lung microvascular permeability and tested this in patients, ex vivo human lungs, and cultured human lung microvascular endothelial cells. In a nested case control study of 40 patients with severe PGD at 72 hours and 80 matched controls without PGD, elevated preoperative CFH was independently associated with increased PGD risk (odds ratio [OR] 2...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29312756/history-of-lung-transplantation
#18
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
#19
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...
March 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
#20
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 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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