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Normothermic Ex vivo perfusion

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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
#1
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
#2
Tiago Noguchi Machuca, Marcelo Cypel, Riccardo Bonato, Jonathan C Yeung, Yi-Min Chun, Stephen Juvet, Guan Zehong, David M Hwang, Manyin Chen, Tomohito Saito, Constantine Harmantas, Beverly Davidson, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
OBJECTIVE: 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. We aimed to determine the safety and immunological and functional benefits of ex vivo adenoviral human IL-10 (AdhIL-10) gene delivery to prevent the development of primary graft dysfunction in a large animal survival model. METHODS: Pig donor lungs were retrieved, preserved for 6 hours at 4oC and then randomly assigned to 4 groups: 1) AdhIL-10 Gene Therapy: 12 hours EVLP + AdhIL-10 intra-bronchial delivery; 2) EVLP-control: 12 hours EVLP; 3) Vector-control: 12 hours EVLP + adenoviral vector intra-bronchial delivery; and 4) Prolonged hypothermic preservation: Additional 12 hours of cold ischemia...
January 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28009782/prolonged-evlp-using-ocs-lung-cellular-and-acellular-perfusates
#3
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
#4
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
#5
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
#6
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
#7
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
#8
N Goldaracena, V N Spetzler, J Echeverri, J M Kaths, V Cherepanov, R Persson, M G 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)...
November 2, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27771093/normothermic-ex-vivo-liver-perfusion-from-donors-after-type-2-cardiac-arrest
#9
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
#10
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
#11
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
#12
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...
September 20, 2016: 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
#13
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...
September 17, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27556578/anti-inflammatory-signaling-during-ex-vivo-liver-perfusion-improves-the-preservation-of-pig-liver-grafts-before-transplantation
#14
Nicolas Goldaracena, Juan Echeverri, Vinzent N Spetzler, Johan M Kaths, Andrew S Barbas, Kristine S Louis, Oyedele A Adeyi, David R Grant, Nazia Selzner, Markus Selzner
Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied...
November 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27526866/transplantation-continuous-normothermic-ex-vivo-perfusion-improves-kidney-graft-function
#15
Ellen F Carney
No abstract text is available yet for this article.
October 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27526656/impact-of-reperfusion-calcium-and-ph-on-the-resuscitation-of-hearts-donated-after-circulatory-death
#16
Christopher White, Emma Ambrose, Alison Müller, Sanaz Hatami, Yun Li, Hoa Le, James Thliveris, Rakesh Arora, Trevor Lee, Ian Dixon, Ganghong Tian, Jayan Nagendran, Larry Hryshko, Darren Freed
BACKGROUND: Hearts donated after circulatory death may represent an additional donor source. The influx of sodium and calcium ions across the sarcolemma play a central role in the pathogenesis of ischemia-reperfusion injury; however, this process may be inhibited if the initial reperfusion solution is rendered hypocalcemic and acidic. We sought to determine the calcium concentration and pH of the initial reperfusion solution that yielded optimal functional recovery of hearts donated after circulatory death during ex vivo heart perfusion...
January 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27495754/organ-pretreatment-with-cytotopic-endothelial-localising-peptides-to-ameliorate-microvascular-thrombosis-perfusion-deficits-in-ex-vivo-renal-haemo-reperfusion-models
#17
Karim Hamaoui, Sally Gowers, Martyn Boutelle, Terry 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 anti-coagulant peptides that localise 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 haemo-reperfusion models...
August 5, 2016: Transplantation
https://www.readbyqxmd.com/read/27479157/eight-hour-continuous-normothermic-ex-vivo-kidney-perfusion-is-a-safe-preservation-technique-for-kidney-transplantation-a-new-opportunity-for-the-storage-assessment-and-repair-of-kidney-grafts
#18
J Moritz Kaths, Juan Echeverri, Nicolas Goldaracena, Kristine S Louis, Yi-Min Chun, Ivan Linares, Aryn Wiebe, Daniel B Foltys, Paul M Yip, Rohan John, Istvan Mucsi, Anand Ghanekar, Darius J Bagli, David R Grant, Lisa A Robinson, Markus Selzner
BACKGROUND: Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation. METHODS: Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation...
September 2016: Transplantation
https://www.readbyqxmd.com/read/27467537/continuous-normothermic-ex-vivo-kidney-perfusion-improves-graft-function-in-donation-after-circulatory-death-pig-kidney-transplantation
#19
J Moritz Kaths, Juan Echeverri, Yi Min Chun, Jun Yu Cen, Nicolas Goldaracena, Ivan Linares, Luke S Dingwell, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa Robinson, Markus Selzner
BACKGROUND: Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques such as normothermic perfusion. METHODS: We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation...
July 27, 2016: Transplantation
https://www.readbyqxmd.com/read/27444694/mesenchymal-stem-cell-treatment-is-associated-with-decreased-perfusate-concentration-of-interleukin-8-during-ex-vivo-perfusion-of-donor-lungs-after-18-hour-preservation
#20
Pierre Mordant, Daisuke Nakajima, Ricardo Kalaf, Ilker Iskender, Lucas Maahs, Paula Behrens, Rafael Coutinho, Rohin K Iyer, John E Davies, Marcelo Cypel, Mingyao Liu, Thomas K Waddell, Shaf Keshavjee
BACKGROUND: Ex vivo lung perfusion (EVLP) presents a unique therapeutic opportunity to administer mesenchymal stromal cells (MSCs) to lung grafts before transplantation. We sought to determine the optimal route and dose of viable human umbilical cord-derived MSCs to be delivered into ex vivo-perfused damaged swine lungs, and to measure their effect on concentration of growth factors and inflammatory mediators. METHODS: Pig lungs were conventionally retrieved, cold preserved for 18 hours, and perfused normothermically ex vivo for 12 hours...
May 6, 2016: Journal of Heart and Lung Transplantation
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