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Normothermic perfusion

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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
#1
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/28040765/classification-and-outcomes-of-extended-arch-repair-for-acute-type-a-aortic-dissection-a-systematic-review-and-meta-analysis
#2
REVIEW
Holly N Smith, Munir Boodhwani, Maral Ouzounian, Richard Saczkowski, Alexander J Gregory, Eric J Herget, Jehangir J Appoo
OBJECTIVES: Distal extent of repair in patients undergoing surgery for acute Type A aortic dissection (ATAAD) is controversial. Emerging hybrid techniques involving open and endovascular surgery have been reported in small numbers by select individual centres. A systematic review and meta-analysis was performed to investigate the outcomes following extended arch repair for ATAAD. A classification system is proposed of the different techniques to facilitate discussion and further investigation...
December 31, 2016: Interactive Cardiovascular and Thoracic Surgery
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/28006866/liver-splitting-during-normothermic-organ-preservation
#4
Jens G Brockmann, Thomas Vogel, Constantin Coussios, Peter J Friend
Classical split liver transplantation has proved a successful means of transplanting children with size-matched organs without reducing the adult cadaveric liver pool. However, the conventional technique of liver splitting after retrieval (ex situ) implies either increasing the ischaemia time of one graft or the logistic problems of simultaneous transplants in a single institution. Splitting the liver in the donor (in situ splitting) minimises cold ischaemia but greatly increases the operating time in the donor hospital and requires highly specialised hepatobiliary expertise at time of organ donation...
December 22, 2016: Liver 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
#5
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/27941468/liver-perfusion-devices-how-close-are-we-to-widespread-application
#6
Amelia J Hessheimer, Constantino Fondevila
PURPOSE OF REVIEW: Ex-situ liver machine perfusion has been the focus of increasing interest over the past decade as a means to improve the quality of livers for transplantation and the applicability of liver transplantation in general. The present review aims to evaluate the experimental basis for liver machine perfusion and the significance of recent reports on its clinical application. RECENT FINDINGS: Although liver machine perfusion has been studied experimentally over a range of temperatures, clinical liver transplant work that has been performed to date has been done using either hypothermic machine perfusion (0-12 °C), HMP or normothermic machine perfusion (35-38 °C, NMP)...
December 9, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27941437/activation-of-fibrinolysis-but-not-coagulation-during-end-ischemic-ex-situ-normothermic-machine-perfusion-of-human-donor-livers
#7
Shanice A Karangwa, Laura C Burlage, Jelle Adelmeijer, Negin Karimian, Andrie C Westerkamp, Alix P M Matton, Rianne van Rijn, Janneke Wiersema-Buist, Michael 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 prior to 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, PAP complex, tPA and PAI-1 (markers for fibrinolysis) and alanine aminotransferase (ALT; marker of ischemia/reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals...
December 8, 2016: Transplantation
https://www.readbyqxmd.com/read/27940566/glucose-regulates-the-intrinsic-inflammatory-response-of-the-heart-to-surgically-induced-hypothermic-ischemic-arrest-and-reperfusion
#8
Ahmed S Bux, Merry L Lindsey, Hernan G Vasquez, Heinrich Taegtmeyer, Romain Harmancey
We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were cold-arrested in Krebs-Henseleit buffer and subjected to 60 minutes normothermic reperfusion in the working mode with buffer supplemented with non-carbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared to that of non-perfused hearts...
December 9, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27917620/normothermic-ex-vivo-lung-perfusion-in-brain-dead-donors-reduces-inflammatory-cytokines-and-toll-like-receptor-expression
#9
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/27916176/functional-assessment-and-transplantation-of-the-donor-heart-after-circulatory-death
#10
Simon J Messer, Richard G Axell, Simon Colah, Paul A White, Marian Ryan, Aravinda A Page, Barbora Parizkova, Kamen Valchanov, Christopher W White, Darren H Freed, Euan Ashley, John Dunning, Martin Goddard, Jayan Parameshwar, Christopher J Watson, Thomas Krieg, Ayyaz Ali, Steven Tsui, Stephen R Large
BACKGROUND: After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program...
December 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27906706/effects-of-cardiopulmonary-bypass-on-renal-perfusion-filtration-and-oxygenation-in-patients-undergoing-cardiac-surgery
#11
Lukas Lannemyr, Gudrun Bragadottir, Vitus Krumbholz, Bengt Redfors, Johan Sellgren, Sven-Erik Ricksten
BACKGROUND: Acute kidney injury is a common complication after cardiac surgery with cardiopulmonary bypass. The authors evaluated the effects of normothermic cardiopulmonary bypass on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen supply/demand relationship, i.e., renal oxygenation (primary outcome) in patients undergoing cardiac surgery. METHODS: Eighteen patients with a normal preoperative serum creatinine undergoing cardiac surgery procedures with normothermic cardiopulmonary bypass (2...
February 2017: Anesthesiology
https://www.readbyqxmd.com/read/27870928/mir-182-5p-inhibition-ameliorates-ischemic-acute-kidney-injury
#12
Julia Wilflingseder, Kíra Jelencsics, Helga Bergmeister, Judith Sunzenauer, Heinz Regele, Farsad Eskandary, Roman Reindl-Schwaighofer, Alexander Kainz, Rainer Oberbauer
Acute kidney injury (AKI) remains a major clinical event with high mortality rates. We previously identified renal miR-182 as the main driver of post-transplantation AKI. Therefore, we tested the causal inference of miR-182 by inhibiting its renal expression in vivo. In 45 rats AKI was induced by right nephrectomy and contralateral clamping of the renal pedicle for 40 minutes. Systemically administered antisense oligonucleotide (ASO) inhibited miR-182 in the kidneys up to 96 hours. The maximum creatinine elevation was on day 2 after injury (mg/dL; median and interquartile range): ASO 2...
January 2017: American Journal of Pathology
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
#13
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/27859779/nicotinic-receptor-activation-augments-muscarinic-receptor-mediated-eccrine-sweating-but-not-cutaneous-vasodilatation-in-young-males
#14
Naoto Fujii, Jeffrey C Louie, Brendan D McNeely, Sarah Y Zhang, My-An Tran, Glen P Kenny
What is the central question of this study? Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors. Although each receptor can independently induce cutaneous vasodilatation and eccrine sweating, it remains to be elucidated whether the two receptors interact in order to mediate these responses. What is the main finding and its importance? We show that although nicotinic receptor activation does not modulate muscarinic cutaneous vasodilatation, it lowers the muscarinic receptor agonist threshold at which onset for eccrine sweating (augmentation of muscarinic eccrine sweating) occurs in young men in normothermic resting conditions...
November 18, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27809409/24-hour-normothermic-machine-perfusion-of-discarded-human-liver-grafts
#15
Thomas Vogel, Jens G Brockmann, Alberto Quaglia, Alireza Morovat, Wayel Jassem, Nigel D Heaton, Constantin C Coussios, Peter J Friend
Background Donor organ shortage necessitates use of less than optimal donor allografts for transplantation. Current cold storage preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation (NMP) of liver allografts. In this study, we analyse discarded human liver grafts that underwent NMP for the extended period of 24 hours. Methods Thirteen human liver grafts which had been discarded for transplantation, were entered into this study...
November 3, 2016: Liver 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
#16
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/27795989/normothermic-machine-perfusion-of-deceased-donor-liver-grafts-is-associated-with-improved-postreperfusion-hemodynamics
#17
Roberta Angelico, M Thamara P R Perera, Reena Ravikumar, David Holroyd, Constantin Coussios, Hynek Mergental, John R Isaac, Asim Iqbal, Hentie Cilliers, Paolo Muiesan, Peter J Friend, Darius F Mirza
BACKGROUND: Graft reperfusion poses a critical challenge during liver transplantation and can be associated with hemodynamic instability/postreperfusion syndrome. This is sequel to ischemia-reperfusion injury and normothermic machine preservation (NMP) may affect hemodynamic changes. Herein, we characterize postreperfusion hemodynamics in liver grafts after NMP and traditional cold preservation. MATERIALS AND METHODS: Intraoperative records of patients receiving grafts after NMP (n = 6; NMP group) and cold storage (CS) (n = 12; CS group) were compared...
September 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27783454/successful-donation-after-cardiac-death-liver-transplants-with-prolonged-warm-ischemia-time-using-normothermic-regional-perfusion
#18
Riccardo De Carlis, Stefano Di Sandro, Andrea Lauterio, Fabio Ferla, Antonio Dell'Acqua, Marinella Zanierato, Luciano De Carlis
The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes...
October 26, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27771093/normothermic-ex-vivo-liver-perfusion-from-donors-after-type-2-cardiac-arrest
#19
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
#20
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
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