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Normothermic Ex vivo perfusion

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https://www.readbyqxmd.com/read/28434548/ex%C3%A2-vivo-lung-perfusion-rehabilitates-sepsis-induced-lung-injury
#1
J Hunter Mehaffey, Eric J Charles, Ashish K Sharma, Morgan Salmon, Dustin Money, Sarah Schubert, Mark H Stoler, Curtis G Tribble, Victor E Laubach, Mark E Roeser, Irving L Kron
BACKGROUND: Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury. METHODS: We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury...
April 20, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28394815/normothermic-ex-vivo-heart-perfusion-effects-of-live-animal-blood-and-plasma-cross-circulation
#2
Joseph T Church, Fares Alghanem, Kristopher B Deatrick, John M Trahanas, Joseph P Phillips, Min Hee Song, Elena M Perkins, Robert H Bartlett, Alvaro Rojas-Pena, Martin L Bocks, Gabe E Owens
Prolonged normothermic ex-vivo heart perfusion (NEVHP) could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via NEVHP. Standard perfusion (n=40) utilized red blood cell/plasma perfusate and Langendorf technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-Blood; n=6) or cross-circulated filtered plasma (XC-Plasma; n=7) between a live paracorporeal pig under anesthesia and the perfusate reservoir...
April 6, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28375588/normothermic-ex-vivo-kidney-perfusion-following-static-cold-storage-ndash-brief-intermediate-or-prolonged-perfusion-for-optimal-renal-graft-reconditioning
#3
J Moritz Kaths, Juan Echeverri, Ivan Linares, Jun Yu Cen, Sujani Ganesh, Matyas Hamar, Peter Urbanellis, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A Robinson, Markus Selzner
Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8h) followed by various periods of NEVKP recovery was investigated: group A) 8hSCS only (control), group B) 8hSCS+1hNEVKP (brief NEVKP), group C) 8hSCS+8hNEVKP (intermediate NEVKP), and group D) 8hSCS+16hNEVKP (prolonged NEVKP)...
April 4, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28361124/lowering-perfusate-temperature-from-37%C3%A2-c-to-32%C3%A2-c-diminishes-function-in-a-porcine-model-of-ex-vivo-kidney-perfusion
#4
Thomas D Adams, Meeta Patel, Sarah A Hosgood, Michael L Nicholson
BACKGROUND: Ex vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS). METHODS: Porcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28322021/cytoprotective-and-antioxidant-effects-of-steen-solution-on-human-lung-spheroids-and-human-endothelial-cells
#5
Francesca Pagano, Cristina Nocella, Sebastiano Sciarretta, Luca Fianchini, Camilla Siciliano, Giorgio Mangino, Mohsen Ibrahim, Elena De Falco, Roberto Carnevale, Isotta Chimenti, Giacomo Frati
Respiratory diseases represent a major healthcare burden worldwide. Lung transplantation (LTx) is the gold-standard for end-stage patients, strongly limited by shortage of available/suitable donor lungs. Normothermic ex vivo lung perfusion (EVLP) has significantly increased the number of lungs suitable for transplantation. Steen solution is used for EVLP, but the mechanisms involved in its beneficial properties remain to be clarified. We investigated the effects of Steen solution in an in vitro protocol of cold starvation and normothermic recovery (CS/NR) on human lung spheroids, named pneumospheres (PSs), containing epithelial/basal cells, and on endothelial HUVEC cells...
March 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28314503/standard-donor-lung-procurement-with-normothermic-ex-vivo-lung-perfusion-a-prospective-randomized-clinical-trial
#6
Alexis Slama, Lukas Schillab, Maximilian Barta, Aris Benedek, Andreas Mitterbauer, Konrad Hoetzenecker, Shahrokh Taghavi, Gyoergy Lang, Jose Matilla, Hendrik Ankersmit, Helmut Hager, Georg Roth, Walter Klepetko, Clemens Aigner
BACKGROUND: Ex vivo lung perfusion (EVLP) was primarily developed for evaluation of impaired donor lungs. The good clinical results raise the question for its possible impact on lungs meeting standard criteria. Before application of EVLP on such lungs enters routine clinical practice, it must be demonstrated whether EVLP would affect or improve outcome when used in standard donor lungs. We performed a prospective randomized trial to investigate the role of EVLP in standard lung transplantation (Tx)...
February 20, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28240817/liver-ex-vivo-machine-perfusion-preservation-a-review-of-the-methodology-and-results-of-large-animal-studies-and-clinical-trials
#7
REVIEW
Hazel Marecki, Adel Bozorgzadeh, Robert Porte, Henri Leuvenink, Korkut Uygun, Paulo Martins
Ex-vivo machine perfusion is a promising way to better preserve livers prior to transplantation. Currently, no methodology has verified benefit over simple cold storage. Before becoming clinically feasible, machine perfusion requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, who's physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored machine perfusion as preservation, but only recently have clinical trials been performed...
February 27, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28115329/protocol-of-a-randomised-controlled-open-label-trial-of-ex-vivo-normothermic-perfusion-versus-static-cold-storage-in-donation-after-circulatory-death-renal-transplantation
#8
Sarah A Hosgood, Kourosh Saeb-Parsy, Colin Wilson, Christopher Callaghan, Dave Collett, Michael L Nicholson
INTRODUCTION: Ex vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice. METHODS AND ANALYSIS: This is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation...
January 23, 2017: BMJ Open
https://www.readbyqxmd.com/read/28052693/safety-and-efficacy-of-ex-vivo-donor-lung-adenoviral-il-10-gene-therapy-in-a-large-animal-lung-transplant-survival-model
#9
Tiago N Machuca, Marcelo Cypel, Riccardo Bonato, Jonathan C Yeung, Yi-Min Chun, Stephen Juvet, Zehong Guan, David M Hwang, Manyin Chen, Tomohito Saito, Constantine Harmantas, Beverly L Davidson, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
Ex vivo normothermic lung perfusion (EVLP) is a novel platform and method developed to facilitate functional assessment and implementation of advanced therapies for donor lungs prior to transplantation. This study aimed to determine the safety and immunological and functional benefits of ex vivo adenoviral human interleukin-10 (AdhIL-10) gene delivery to prevent the development of primary graft dysfunction in a large animal survival model. Pig donor lungs were retrieved, preserved for 6 h at 4°C, and then randomly assigned to four groups: (1) AdhIL-10 gene therapy: 12 h EVLP + AdhIL-10 intra-bronchial delivery; (2) EVLP-control: 12 h EVLP; (3) Vector-control: 12 h EVLP + adenoviral vector intra-bronchial delivery; and (4) prolonged hypothermic preservation: additional 12 h of cold ischemia...
January 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28009782/prolonged-evlp-using-ocs-lung-cellular-and-acellular-perfusates
#10
Gabriel Loor, Brian T Howard, John R Spratt, Lars M Mattison, Angela Panoskaltsis-Mortari, Roland Z Brown, Tinen L Iles, Carolyn M Meyer, Haylie Helms, Andrew Price, Paul A Iaizzo
BACKGROUND: We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits. METHODS: Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform...
December 22, 2016: Transplantation
https://www.readbyqxmd.com/read/27993213/an-ex%C3%A2-vivo-comparison-of-adenosine-and-lidocaine-solution-and-university-of-wisconsin-solution-for-hypothermic-machine-perfusion-of-porcine-kidneys-potential-for-development
#11
Karim Hamaoui, Adeel Aftab, Sally Gowers, Martyn Boutelle, Terry Cook, Donna Rudd, Geoffrey P Dobson, Vassilios Papalois
BACKGROUND: The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca(2+), 16 mM Mg(2+), and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). METHODS: Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27941437/activation-of-fibrinolysis-but-not-coagulation-during-end-ischemic-ex-situ-normothermic-machine-perfusion-of-human-donor-livers
#12
Shanice A Karangwa, Laura C Burlage, Jelle Adelmeijer, Negin Karimian, Andrie C Westerkamp, Alix P Matton, Rianne van Rijn, Janneke Wiersema-Buist, Micheal E Sutton, Sanna Op den Dries, Ton Lisman, Robert J Porte
BACKGROUND: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability before transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo. METHODS: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid. Concentration of prothrombin fragment F1 + 2 (marker of coagulation activation), D-dimer, plasmin-antiplasmin complex, tissue plasminogen activator and plasminogen activator inhibitor-1 (markers for fibrinolysis) and alanine aminotransferase (ALT) (marker of ischemia-reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals...
February 2017: Transplantation
https://www.readbyqxmd.com/read/27917620/normothermic-ex-vivo-lung-perfusion-in-brain-dead-donors-reduces-inflammatory-cytokines-and-toll-like-receptor-expression
#13
Shadi Shafaghi, Esmaeil Mortaz, Azizollah Abbasi Dezfuli, Hoda Godarzi, Kambiz Sheikhy, Zahra Ansari Aval, Behrooz Farzanegan, Habib Emami, Fatemeh Sadat Hosseini-Baharanchi, Katayoun Najafizadeh
Inflammatory responses and innate immunologic reactions play an important role in the respiratory system. Ex vivo lung perfusion (EVLP) is considered a novel method in the evaluation and reconditioning of donor lungs prior to transplantation. However, EVLP's effect on inflammatory and metabolic markers of human lung tissue is unknown.  This study investigated how the performance of EVLP on brain-dead (BD) donor lungs affects the production and release of inflammatory cytokines (IL-6, IL-8, and TNF-a), inflammatory cells and toll-like receptors (TLR) -2, 4...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27861293/organ-pretreatment-with-cytotopic-endothelial-localizing-peptides-to-ameliorate-microvascular-thrombosis-and-perfusion-deficits-in-ex-vivo-renal-hemoreperfusion-models
#14
Karim Hamaoui, Sally Gowers, Martyn Boutelle, Terry H Cook, George Hanna, Ara Darzi, Richard Smith, Anthony Dorling, Vassilios Papalois
BACKGROUND: Hypothermic machine organ perfusion (HMP) offers opportunity to manipulate grafts with pharmacological agents prior to transplantation. Pretreating organs with novel cytotopic anticoagulant peptides that localize to endothelial cell membranes could ameliorate microvascular thrombotic sequelae posttransplantation. We describe experiments testing thrombalexin (TLN), a novel cell binding thrombin inhibitor, using porcine and unused human kidneys in a series of ex vivo normothermic hemoreperfusion models...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27805315/inducing-hepatitis-c-virus-resistance-after-pig-liver-transplantation-a-proof-of-concept-of-liver-graft-modification-using-warm-ex-vivo-perfusion
#15
N Goldaracena, V N Spetzler, J Echeverri, J M Kaths, V Cherepanov, R Persson, M R Hodges, H L A Janssen, N Selzner, D R Grant, J J Feld, M Selzner
Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS)...
April 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27771093/normothermic-ex-vivo-liver-perfusion-from-donors-after-type-2-cardiac-arrest
#16
Mihai-Calin Pavel, Constantino Fondevila Campo, Victor Molina Santos, Alba Diaz Lorca, Juan Carlos Garcia-Valdecasas Salgado
No abstract text is available yet for this article.
October 19, 2016: Cirugía Española
https://www.readbyqxmd.com/read/27768055/methods-for-the-determination-of-rates-of-glucose-and-fatty-acid-oxidation-in-the-isolated-working-rat-heart
#17
Bhavisha Bakrania, Joey P Granger, Romain Harmancey
The mammalian heart is a major consumer of ATP and requires a constant supply of energy substrates for contraction. Not surprisingly, alterations of myocardial metabolism have been linked to the development of contractile dysfunction and heart failure. Therefore, unraveling the link between metabolism and contraction should shed light on some of the mechanisms governing cardiac adaptation or maladaptation in disease states. The isolated working rat heart preparation can be used to follow, simultaneously and in real time, cardiac contractile function and flux of energy providing substrates into oxidative metabolic pathways...
September 28, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27681269/an-assessment-of-urinary-biomarkers-in-a-series-of-declined-human-kidneys-measured-during-ex-vivo-normothermic-kidney-perfusion
#18
Sarah A Hosgood, Michael L Nicholson
BACKGROUND: The measurement of urinary biomarkers during ex-vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output...
September 27, 2016: Transplantation
https://www.readbyqxmd.com/read/27647696/continuous-normothermic-ex-vivo-kidney-perfusion-is-superior-to-brief-normothermic-perfusion-following-static-cold-storage-in-donation-after-circulatory-death-pig-kidney-transplantation
#19
J M Kaths, J Y Cen, Y M Chun, J Echeverri, I Linares, S Ganesh, P Yip, R John, D Bagli, I Mucsi, A Ghanekar, D R Grant, L A Robinson, M Selzner
Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP...
April 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27639262/preliminary-single-center-canadian-experience-of-human-normothermic-ex-vivo-liver-perfusion-results-of-a-clinical-trial
#20
M Bral, B Gala-Lopez, D Bigam, N Kneteman, A Malcolm, S Livingstone, A Andres, J Emamaullee, L Russell, C Coussios, L J West, P J Friend, A M J Shapiro
After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single-center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded...
April 2017: American Journal of Transplantation
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