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Ex vivo lung perfusion

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...
March 5, 2018: Surgery
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
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
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
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...
February 9, 2018: Xenotransplantation
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
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 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...
January 30, 2018: Current Opinion in Organ Transplantation
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...
January 29, 2018: Expert Review of Medical Devices
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
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
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
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
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
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
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...
March 2018: European Journal of Pharmaceutics and Biopharmaceutics
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
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
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
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
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
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