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Ex vivo perfusion

Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
Maudy Walraven, Marjolein Y V Homs, Astrid A M van der Veldt, Henk Dekker, Jose Koldenhof, Richard Honeywell, Arjan Barendrecht, Silvie A E Sebastian, Naomi Parr, Arnold C Koekman, Emile E Voest, Mark Roest, Suzanne J A Korporaal, Henk M W Verheul
INTRODUCTION: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings...
March 12, 2018: Angiogenesis
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
Giulia Maria Ruggeri, Joshua Qua Hiansen, Emanuele Pivetta, Azad Mashari, Flavia Ballocca, Roberto Vanin Pinto Ribeiro, Liming Xin, Mitesh Badiwala, Babita Thampinathan, Massimiliano Meineri
Ex vivo heart perfusion (EVHP) is a new technology aimed at decreasing cold ischemia time and evaluating cardiac function before transplanting a donor heart. In an experimental EVHP swine model, we tested a 3D-printed custom-made set-up to perform surface echocardiography on an isolated beating heart during left ventricular loading. The views obtained at any time point were equivalent to standard transesophageal and transthoracic views. A decrease in left ventricular function during EVHP was observed in all experiments...
March 1, 2018: Anesthesia and Analgesia
Tian-Rui Yang, Yun-Bo Miao, Rong-Ping Zhang, Jin-Wen Yu
OBJECTIVE: To establish an ex vivo model of myocardial ischemia reperfusion in tree shrews. METHODS: The Langendorff ex vivo heart perfusion system was used to establish the myocardial ischemia reperfusion model in tree shrews with different irrigation and reperfusion time settings. Alanine aminotransferase (ALT), aspartate transaminase (AST) and lactic dehydrogenase (LDH) levels were measured by enzyme-labeled immunosorbent assay, creatine kinase MB (CK-MB) was detected using immunosuppression method, and malondialdehyde was measured with thiobarbital staining method; the infarct size was measured using 2, 3, 5-triphenyltrazoliumchloride (TTC) method...
February 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Maria Monteagudo Vela, Diana García Sáez, Andre R Simon
Fifty years after the first successful heart transplantation, despite multiple advances in the treatment of advanced acute and chronic heart failure, there is still no equivalent to heart transplantation as a long-term treatment for end-stage heart failure. Transplantation is, however, limited by the scarcity and quality of heart allografts. Donors are nowadays significantly older, particularly in European countries, and traumatic head injury as the cause of death has been replaced by intracerebral hemorrhage or hypoxic brain damage in the majority of cases...
January 2018: Annals of Cardiothoracic Surgery
Aileen Hoehne, Michelle L James, Israt S Alam, John A Ronald, Bernadette Schneider, Aloma D'Souza, Timothy H Witney, Lauren E Andrews, Haley C Cropper, Deepak Behera, Gayatri Gowrishankar, Zhaoqing Ding, Tony Wyss-Coray, Frederick T Chin, Sandip Biswal, Sanjiv S Gambhir
BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55 ) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin...
February 22, 2018: Journal of Neuroinflammation
Christin Neuber, Birgit Belter, Sebastian Meister, Frank Hofheinz, Ralf Bergmann, Hans-Jürgen Pietzsch, And Jens Pietzsch
Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron emission tomography. Vascularization was investigated by fluorescence imaging in vivo and ex vivo. The approach was completed by magnetic resonance imaging, radioluminography ex vivo, and immunohistochemical staining for blood and lymph vessel markers...
February 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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
Wiktor S Phillips, Christopher A Del Negro, Jens C Rekling
The brainstem preBötzinger complex (preBötC) generates the inspiratory rhythm for breathing. The onset of neural activity that precipitates the inspiratory phase of the respiratory cycle may depend on the activity of type-1 preBötC neurons, which exhibit a transient outward K+ current, IA Inspiratory rhythm generation can be studied ex vivo since the preBötC remains rhythmically active in vitro , both in acute brainstem slices and organotypic cultures. Advantageous optical conditions in organotypic slice cultures from newborn mice of either sex allowed us to investigate how IA impacts Ca2+ transients occurring in the dendrites of rhythmically active type-1 preBötC neurons...
February 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tian-Qi Zhang, Sen-Miao Huang, Yang-Kui Gu, Fei Gao, Zhi-Mei Huang, Xiong-Ying Jiang, Ding-Xin Liu, Jin-Hua Huang
PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissue, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103°C and 30 W for 3 minutes. For each experimental setting, 6 ablations were created...
February 18, 2018: International Journal of Hyperthermia
Xiangyu Zou, Kai Jiang, Amrutesh S Puranik, Kyra L Jordan, Hui Tang, Xiangyang Zhu, Lilach O Lerman
Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery...
February 15, 2018: Stem Cells Translational Medicine
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
Federica Rigo, Nicola De Stefano, Victor Navarro-Tableros, Ezio David, Giorgia Rizza, Giorgia Catalano, Nicholas Gilbo, Francesca Maione, Federica Gonella, Dorotea Roggio, Silvia Martini, Damiano Patrono, Mauro Salizzoni, Giovanni Camussi, Renato Romagnoli
BACKGROUND: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS: We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution...
February 9, 2018: Transplantation
Hyun-Ji Park, Rui Kuai, Eun Je Jeon, Yoojin Seo, Youngmee Jung, James J Moon, Anna Schwendeman, Seung-Woo Cho
Therapeutic strategies using endogenous stem cell mobilizer can provide effective cell-free therapy for addressing various ischemic diseases. In particular, substance P (SP) exhibited therapeutic regeneration by facilitating mobilization of endogenous stem cells from bone marrow to the injured sites. However, its therapeutic effect has been limited due to short half-life and rapid degradation of administered SP peptides in vivo. Here we sought to develop high-density lipoprotein (HDL)-mimicking nanodiscs conjugated with SP (HDL-SP) in order to increase the in vivo half-life, bone marrow targeting, and therapeutic efficacy of SP for the treatment of diabetic peripheral ischemia...
January 19, 2018: Biomaterials
Wangzhong Sheng, William J Seare, Barry DiBernardo, Ali H Alhasan, Esther Cory, Paul Chasan, Robert L Sah, Khalid M Almutairi, Adah Almutairi
Background: Liposuction is one of the most performed cosmetic surgery procedures. In a previously reported study, gold-nanoparticle (GNP) laser-assisted liposuction (NanoLipo) was shown to improve procedure parameters and outcomes in a porcine model. Objective: An ex vivo human liposuction model was developed to assess the ease, efficacy, and outcomes of NanoLipo, and to further explore its mechanism of action in facilitating liposuction. Methods: NanoLipo was compared to a Control without GNPs in sets of fresh, non-perfused, anatomically-symmetric, matched tissue specimens from 12 patients...
February 3, 2018: Aesthetic Surgery Journal
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
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