المؤلفون: Ceilidh McKenney, Julia Torabi, Rachel Todd, M. Zeeshan Akhtar, Fasika M. Tedla, Ron Shapiro, Sander S. Florman, Matthew L. Holzner, L. Leonie van Leeuwen

المصدر: Transplantology, Vol 5, Iss 2, Pp 51-64 (2024)

مصطلحات موضوعية: kidney transplantation, organ donation, organ discard, donation after circulatory death, organ procurement organization, hypothermic machine perfusion, Surgery, RD1-811

الوصف: Kidney transplantation is a life-saving intervention for end-stage renal disease; yet, the persistent gap between organ demand and supply remains a significant challenge. This paper explores the escalating discard rates of deceased donor kidneys in the United States to assess trends, discard reasons, demographical differences, and preservation techniques. Data from the Scientific Registry of Transplant Recipients from 2010 to 2021 was analyzed using chi-squared tests for trend significance and logistic regression to estimate odds ratios for kidney discard. Over the last decade, discard rates have risen to 25% in 2021. Most discarded kidneys came from extended criteria donor (ECD) donors and elevated kidney donor profile index (KDPI) scores. Kidney biopsy status was a significant factor and predictor of discard. Discard rates varied greatly between Organ Procurement and Transplantation Network regions. Of reasons for discard, “no recipient located” reached a high of 60%. Additionally, there has been a twofold increase in hypothermic machine perfusion (HMP) since 2010, with transportation difficulties being the main reason for the discard of perfused kidneys. Our findings suggest a need to recalibrate organ utilization strategies, optimize the use of lower-quality kidneys through advanced preservation methods, and address the evolving landscape of organ allocation policies to reduce kidney discard rates.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2673-3943/5/2/6Test; https://doaj.org/toc/2673-3943Test

الوصول الحر: https://doaj.org/article/6741d89d545b4fb18a49980e610279d0Test

المؤلفون: Kristina Andrijauskaite, Rafael J. Veraza, Riley P. Lopez, Zach Maxwell, Isabella Cano, Exal E. Cisneros, Israel J. Jessop, Maria Basurto, George Lamberson, Michelle D. Watt, Joseph Nespral, Masahiro Ono, Leonid Bunegin

المصدر: Frontiers in Cardiovascular Medicine, Vol 11 (2024)

مصطلحات موضوعية: organ preservation, hypothermic machine perfusion, cardiac grafts, heart transplant, VP.S ENCORE® preservation device, deceased DBD donors, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: IntroductionHeart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.S ENCORE®, to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE® using deceased donors derived hearts.MethodsHearts from brain-dead donors not utilized for transplant (n = 11) were offered for research from the Texas Organ Sharing Alliance (TOSA), South and Central Texas' Organ Procurement Organization (OPO) and were preserved in the VP.S ENCORE® for 4 (n = 2), 6 (n = 3), and 8 (n = 3) hours or were kept in static cold storage (SCS) (n = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function.ResultsThe mean donor age was 37.82 ± 12.67 with the youngest donor being 19 and the oldest donor being 58 years old. SCS hearts mean weight gain (%) was −1.4 ± 2.77, while perfused at 4 h was 5.6 ± 6.04, perfused at 6 h 2.1 ± 6.04, and 8 h was 7.2 ± 10.76. Venous and arterial lactate concentrations were less than 2.0 mmol/L across all perfused hearts. Left ventricular contractility (+dPdT, mmHg/s) for 4 h (1,214 ± 1,064), 6 (1,565 ± 141.3), and 8 h (1,331 ± 403.6) were within the range of healthy human heart function. Thus, not significant as compared to the SCS group (1,597 ± 342.2). However, the left ventricular relaxation (mmHg/s) was significant in 6-hour perfused heart (p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2024.1376101/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/580ff6c92bf7437aaa688c4bf9ea2d2aTest

المؤلفون: Simon R. Knight, John M. O’Callaghan

المصدر: Transplant International, Vol 37 (2024)

مصطلحات موضوعية: kidney transplantation, hypothermic machine perfusion, randomised controlled trial, lung transplantation, belatacept, Specialties of internal medicine, RC581-951

وصف الملف: electronic resource

العلاقة: https://www.frontierspartnerships.org/articles/10.3389/ti.2024.12711/fullTest; https://doaj.org/toc/1432-2277Test

الوصول الحر: https://doaj.org/article/a40e96b2f2a847568a5aa0c6a6f8ddf9Test

المؤلفون: Isabel M.A. Brüggenwirth, Veerle A. Lantinga, Bianca Lascaris, Adam M. Thorne, Mark Meerdink, Ruben H. de Kleine, Hans Blokzijl, Aad P. van den Berg, Koen M.E.M. Reyntjens, Ton Lisman, Robert J. Porte, Vincent E. de Meijer, Cyril Moers, Diethard Monbaliu, Sijbrand H. Hofker, Jan Bottema, Hildegaard S. Franke, Marieke T. de Boer, Anne Loes van den Boom, Carlijn I. Buis, Suomi M.G. Fouraschen, Frederik J.H. Hoogwater, Joost M. Klaase, Ruben H.J. de Kleine, Maarten W. Nijkamp, A. Michel Rayar, Frans J.C. Cuperus, Frans van der Heide, Frederike G.I. van Vilsteren, Ilhama F. Abbasova, Meine H. Fernhout, Peter Meyer, Ernesto R.R. Muskiet, Jaap J. Vos, Miriam Zeillemaker, Martijn P.D. Haring, Carol C. Pamplona, Vivianne Veenma, Otto B. van Leeuwen, Silke B. Bodewes, Jelle Adelmeijer, Janneke Wiersema-Buist, Marius van den Heuvel

المصدر: EClinicalMedicine, Vol 68, Iss , Pp 102411- (2024)

مصطلحات موضوعية: Liver transplantation, Machine perfusion, Machine preservation, Clinical trial, Hypothermic machine perfusion, IDEAL stage 2, Medicine (General), R5-920

الوصف: Summary: Background: Liver transplantation is traditionally performed around the clock to minimize organ ischemic time. However, the prospect of prolonging preservation times holds the potential to streamline logistics and transform liver transplantation into a semi-elective procedure, reducing the need for nighttime surgeries. Dual hypothermic oxygenated machine perfusion (DHOPE) of donor livers for 1–2 h mitigates ischemia-reperfusion injury and improves transplant outcomes. Preclinical studies have shown that DHOPE can safely extend the preservation of donor livers for up to 24 h. Methods: We conducted an IDEAL stage 2 prospective clinical trial comparing prolonged (≥4 h) DHOPE to conventional (1–2 h) DHOPE for brain-dead donor livers, enabling transplantation the following morning. Liver allocation to each group was based on donor hepatectomy end times. The primary safety endpoint was a composite of all serious adverse events (SAE) within 30 days after transplantation. The primary feasibility endpoint was defined as the number of patients assigned and successfully receiving a prolonged DHOPE-perfused liver graft. Trial registration at: WHO International Clinical Trial Registry Platform, number NL8740. Findings: Between November 1, 2020 and July 16, 2022, 24 patients were enrolled. The median preservation time was 14.5 h (interquartile range [IQR], 13.9–15.5) for the prolonged group (n = 12) and 7.9 h (IQR, 7.6–8.6) for the control group (n = 12; p = 0.01). In each group, three patients (25%; 95% CI 3.9–46%, p = 1) experienced a SAE. Markers of ischemia-reperfusion injury and oxidative stress in both perfusate and recipients were consistently low and showed no notable discrepancies between the two groups. All patients assigned to either the prolonged group or control group successfully received a liver graft perfused with either prolonged DHOPE or control DHOPE, respectively. Interpretation: This first-in-human clinical trial demonstrates the safety and feasibility of DHOPE in prolonging the preservation time of donor livers to enable daytime transplantation. The ability to extend the preservation window to up to 20 h using hypothermic oxygenated machine preservation at a 10 °C temperature has the potential to reshape the landscape of liver transplantation. Funding: University Medical Center Groningen, the Netherlands.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589537023005886Test; https://doaj.org/toc/2589-5370Test

الوصول الحر: https://doaj.org/article/29158e4bdd724fc08b40eb8e81f7654aTest

المؤلفون: Fuller, Barry J, Green, Colin C

المصدر: Cryoletters , 45 (3) pp. 139-148. (2024)

مصطلحات موضوعية: Hypothermic machine perfusion, isochoric preservation, nanotechnology, organ preservation, organ cryopreservation, oxidative stress, preservation solutions

الوصف: It is some 50 years since the first published reports appeared of ex vivo preservation of organs for transplantation. Over the intervening decades, organ preservation strategies have become one essential component of world-wide clinical transplant services. In the formative years, translational research in organ hypothermic preservation was grappling with the questions about whether static or dynamic storage was preferable, and the practical implications of those choices. Those studies were also informing the newly expanding clinical transplant services. During the middle years, both preservation modalities were practiced by individual group choices. By the 2000???s, the shift in donor demographics demanded a re-evaluation of organ preservation strategies, and now a new era of research and development is promoting adoption of new technologies. In this review we outline many important academic studies which have contributed to this successful history, and give profile to the increasing innovative approaches which are being evaluated for the future.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10192459/1/The%20cold%20chain%20delivery%20of%20organs%20for%20transplantation.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10192459Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10192459/1/The%20cold%20chain%20delivery%20of%20organs%20for%20transplantation.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10192459Test/

المؤلفون: Aurore Ughetto, François Roubille, Adrien Molina, Pascal Battistella, Philippe Gaudard, Roland Demaria, Julien Guihaire, Alain Lacampagne, Clément Delmas

المصدر: Frontiers in Cardiovascular Medicine, Vol 10 (2023)

مصطلحات موضوعية: PGF primary graft failure, MP machine perfusion, ESNP ex situ normothermic perfusion, heart tranplantation, heart preservation, hypothermic machine perfusion (HMP), Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2023.1248606/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/53b23874836e4529aa1f0633224f5ee2Test

المؤلفون: Dimitris Kounatidis, Vassiliki Brozou, Dimitris Anagnostopoulos, Constantinos Pantos, Athanasios Lourbopoulos, Iordanis Mourouzis

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 23, p 16693 (2023)

مصطلحات موضوعية: cardioplegia, static cold storage, heart transplantation, hypothermic machine perfusion, kinases, normothermic machine perfusion, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/23/16693Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/08cd2f31f7944f7d968158fe5b99b461Test

المؤلفون: Wen Hou, Shuang Yang, Jiansen Lu, Yuan Shi, Jing Chen, Decheng Chen, Fei Wang, Lei Liu

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: hypothermic machine perfusion, intestinal transplantation, ischemia reperfusion (I/R) injury, pig, TLR4/NF κB pathway, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundIntestinal transplantation (IT) has become an important procedure for the treatment of irreversible intestinal failure. However, IT is extremely vulnerable to ischemia–reperfusion injury (IRI). Due to the limitations of static cold storage (SCS), hypothermic machine perfusion (HMP) is rapidly gaining popularity. In this study, the intestinal HMP system is established and HMP is compared with SCS.MethodsAn intestinal HMP system was built. Ten miniature pigs were randomly divided into the HMP and SCS groups, and their intestines were perfused using the HMP device and SCS, respectively, followed by orthotopic auto-transplantation. Analysis was done on the grafts between the two groups.ResultsOperation success rates of the surgery were 100% in both groups. The 7-day survival rate was 100% in the HMP group, which was significantly higher than that of the SCS group (20%, P< 0.05). The pathological results showed that fewer injuries of grafts were in the HMP group. Endotoxin (ET), IL-1, IL-6, IFN-γ and TNF-α levels in the HMP group were significantly lower than in the SCS group (P

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117292/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/d147f5f683884f63b44dae58e958871dTest

المؤلفون: Anna Radajewska, Jakub Szyller, Anna Krzywonos-Zawadzka, Agnieszka Olejnik, Grzegorz Sawicki, Iwona Bil-Lula

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14772 (2023)

مصطلحات موضوعية: kidney graft, hypothermic machine perfusion, MitoQ, ischemia–reperfusion injury, oxidative stress, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia–reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an ‘on pump’ therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/19/14772Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/ea029f29c03e40388ee4e94fcdc71312Test

المؤلفون: Hiroyoshi Iwata, Hiromichi Obara, Tetsuya Nakajo, Hiroki Kaneko, Yuga Okazawa, Nur Khatijah Mohd Zin, Hiroki Bochimoto, Makito Ohashi, Yoko Kawada, Mizuho Ohara, Hideki Yokoo, Naoto Matsuno

المصدر: Journal of Clinical Medicine, Vol 12, Iss 18, p 6031 (2023)

مصطلحات موضوعية: donation after cardiac death, extracorporeal membrane oxygenation, hypothermic machine perfusion, liver, scanning electron microscopy, Medicine

الوصف: Grafts from donors after cardiac death (DCD) have greatly contributed to expanding the donor organ pool. This study aimed to determine the benefits of subnormothermic extracorporeal membrane oxygenation (ECMO) and hypothermic machine perfusion (HMP) in a porcine model of DCD liver. Female domestic crossbred Large Yorkshire and Landrace pigs weighing approximately 20 kg were used. The abdominal aorta and inferior vena cava were cannulated and connected to an ECMO circuit for in situ perfusion of the abdominal organs at 22 °C for 60 min, 45 min after cardiac death. The pigs were divided into the cold storage (CS) group (n = 3), where liver grafts were preserved at 4 °C, and the HMP group (n = 3), where liver grafts were preserved by HMP at 8–10 °C. After 4 h of preservation, liver function was evaluated using an isolated liver reperfusion model for 2 h. Although the difference was insignificant, the liver effluent enzyme levels in the HMP group were lower than those in the CS group. Furthermore, morphological findings showed fewer injured hepatocytes in the HMP group than in the CS group. The combined use of in situ subnormothermic ECMO and HMP was beneficial for the functional improvement of DCD liver grafts.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2077-0383/12/18/6031Test; https://doaj.org/toc/2077-0383Test

الوصول الحر: https://doaj.org/article/cc194d9405404ac5bfef787ea495e49fTest