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Knijff LWD, van Kooten C, Ploeg RJ. The Effect of Hypothermic Machine Perfusion to Ameliorate Ischemia-Reperfusion Injury in Donor Organs. Front Immunol 2022; 13:848352. [PMID: 35572574 PMCID: PMC9099247 DOI: 10.3389/fimmu.2022.848352] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 04/04/2022] [Indexed: 12/23/2022] Open
Abstract
Hypothermic machine perfusion (HMP) has become the new gold standard in clinical donor kidney preservation and a promising novel strategy in higher risk donor livers in several countries. As shown by meta-analysis for the kidney, HMP decreases the risk of delayed graft function (DGF) and improves graft survival. For the liver, HMP immediately prior to transplantation may reduce the chance of early allograft dysfunction (EAD) and reduce ischemic sequelae in the biliary tract. Ischemia-reperfusion injury (IRI), unavoidable during transplantation, can lead to massive cell death and is one of the main causes for DGF, EAD or longer term impact. Molecular mechanisms that are affected in IRI include levels of hypoxia inducible factor (HIF), induction of cell death, endothelial dysfunction and immune responses. In this review we have summarized and discussed mechanisms on how HMP can ameliorate IRI. Better insight into how HMP influences IRI in kidney and liver transplantation may lead to new therapies and improved transplant outcomes.
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Affiliation(s)
- Laura W. D. Knijff
- Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, Netherlands
- Transplant Centre of the Leiden University Medical Centre, Leiden University Medical Centre, Leiden, Netherlands
| | - Cees van Kooten
- Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, Netherlands
- Transplant Centre of the Leiden University Medical Centre, Leiden University Medical Centre, Leiden, Netherlands
| | - Rutger J. Ploeg
- Transplant Centre of the Leiden University Medical Centre, Leiden University Medical Centre, Leiden, Netherlands
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
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Rampes S, Ma D. Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies. J Biomed Res 2019; 33:221-234. [PMID: 32383437 DOI: 10.7555/jbr.32.20180087] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hepatic ischemia-reperfusion injury is a major cause of liver transplant failure, and is of increasing significance due to increased use of expanded criteria livers for transplantation. This review summarizes the mechanisms and protective strategies for hepatic ischemia-reperfusion injury in the context of liver transplantation. Pharmacological therapies, the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies. The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemia-reperfusion injury, and is an exciting and active area of research, which needs more study clinically.
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Affiliation(s)
- Sanketh Rampes
- Faculty of Life Sciences & Medicine, King's College London, London SE1 1U, UK
| | - Daqing Ma
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK
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3
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Schlegel A, Muller X, Dutkowski P. Hypothermic Machine Preservation of the Liver: State of the Art. CURRENT TRANSPLANTATION REPORTS 2018; 5:93-102. [PMID: 29564206 PMCID: PMC5843682 DOI: 10.1007/s40472-018-0183-z] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW In this review, we highlight which livers may benefit from additional treatment before implantation and describe the concept of hypothermic machine liver perfusion. Furthermore, we explain why cold oxygenated perfusion concepts could potentially lead to a breakthrough in this challenging field of transplantation. Accordingly, we summarize recent clinical applications of different hypothermic perfusion approaches. RECENT FINDINGS The impact of end-ischemic, hypothermic liver perfusion in liver transplantation is currently assessed by two multicenter, randomized controlled trials. Recently, new applications of hypothermic perfusion showed promising results and recipients were protected from severe intrahepatic biliary complications, despite the use of very extended criteria grafts including donation after circulatory death livers. SUMMARY Hypothermic machine liver perfusion is beneficial for high-risk livers and protects recipients from most feared complications. Importantly, such easy approach is currently implemented in several European centers and new markers obtained from perfusate may improve the prediction of liver function in the future.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
- NIHR Liver Biomedical Research Unit, University Hospitals Birmingham, Birmingham, UK
| | - Xavier Muller
- Department of Surgery & Transplantation, Swiss HPB and Transplant Center, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery & Transplantation, Swiss HPB and Transplant Center, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
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4
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Karangwa SA, Dutkowski P, Fontes P, Friend PJ, Guarrera JV, Markmann JF, Mergental H, Minor T, Quintini C, Selzner M, Uygun K, Watson CJ, Porte RJ. Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines. Am J Transplant 2016; 16:2932-2942. [PMID: 27129409 PMCID: PMC5132023 DOI: 10.1111/ajt.13843] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 03/28/2016] [Accepted: 04/19/2016] [Indexed: 02/06/2023]
Abstract
With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta-analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures.
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Affiliation(s)
- S. A. Karangwa
- Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
- Surgical Research LaboratoryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
| | - P. Dutkowski
- Department of Surgery & TransplantationUniversity Hospital ZurichZurichSwitzerland
| | - P. Fontes
- Thomas E. Starzl Transplantation Institute Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPA
- McGowan Institute of Regenerative MedicineUniversity of PittsburghPittsburghPA
| | - P. J. Friend
- Nuffield Department of SurgeryOxford Transplant CentreUniversity of OxfordChurchill HospitalOxfordUK
| | - J. V. Guarrera
- Department of SurgeryCenter for Liver Disease and TransplantationColumbia University Medical CenterNew YorkNY
| | | | - H. Mergental
- Liver UnitUniversity Hospital BirminghamBirminghamUK
| | - T. Minor
- Department of Surgical ResearchClinic for General Visceral and Transplantation SurgeryUniversity Hospital EssenEssenGermany
| | - C. Quintini
- Department of SurgeryTransplant CenterDigestive Disease InstituteCleveland Clinic FoundationClevelandOH
| | - M. Selzner
- Department of SurgeryMulti Organ Transplant ProgramToronto General HospitalTorontoONCanada
| | - K. Uygun
- Department of SurgeryCenter for Engineering in MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA
| | - C. J. Watson
- University of Cambridge Department of Surgery and the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation University of CambridgeAddenbrooke's HospitalCambridgeUK
| | - R. J. Porte
- Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
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5
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Folch-Puy E, Panisello A, Oliva J, Lopez A, Castro Benítez C, Adam R, Roselló-Catafau J. Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury. Int J Mol Sci 2016; 17:807. [PMID: 27231901 PMCID: PMC4926341 DOI: 10.3390/ijms17060807] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 05/15/2016] [Accepted: 05/17/2016] [Indexed: 02/07/2023] Open
Abstract
The endoplasmic reticulum (ER) is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS). This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR), which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI) of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes.
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Affiliation(s)
- Emma Folch-Puy
- Experimental Pathology Department, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC), Rosselló 161, 08036-Barcelona, Catalonia, Spain.
| | - Arnau Panisello
- Experimental Pathology Department, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC), Rosselló 161, 08036-Barcelona, Catalonia, Spain.
| | - Joan Oliva
- Department of Medicine, LaBioMed at Harbor UCLA Medical Center, Torrance, 90502 CA, USA.
| | - Alexandre Lopez
- Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Inserm U935, Université Paris-Sud, Villejuif, 75008 Paris, France.
| | - Carlos Castro Benítez
- Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Inserm U935, Université Paris-Sud, Villejuif, 75008 Paris, France.
| | - René Adam
- Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Inserm U935, Université Paris-Sud, Villejuif, 75008 Paris, France.
| | - Joan Roselló-Catafau
- Experimental Pathology Department, Instituto de Investigaciones Biomédicas de Barcelona, Spanish Research Council (IIBB-CSIC), Rosselló 161, 08036-Barcelona, Catalonia, Spain.
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6
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Schlegel A, Kron P, Dutkowski P. Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application. CURRENT TRANSPLANTATION REPORTS 2015; 2:52-62. [PMID: 26097802 PMCID: PMC4469295 DOI: 10.1007/s40472-014-0046-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion.
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Affiliation(s)
- A. Schlegel
- Department of Surgery and Transplantation, University Hospital Zürich, Raemistr. 100, 8091 Zurich, Switzerland
| | - P. Kron
- Department of Surgery and Transplantation, University Hospital Zürich, Raemistr. 100, 8091 Zurich, Switzerland
| | - P. Dutkowski
- Department of Surgery and Transplantation, University Hospital Zürich, Raemistr. 100, 8091 Zurich, Switzerland
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7
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Bazerbachi F, Selzner N, Seal JB, Selzner M. Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge. World J Transl Med 2014; 3:58-68. [DOI: 10.5528/wjtm.v3.i2.58] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/11/2014] [Accepted: 07/17/2014] [Indexed: 02/05/2023] Open
Abstract
The scarcity of donor livers has increased the interest in donation after cardiac death (DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusion models, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.
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Corwin WL, Baust JM, Baust JG, Van Buskirk RG. Characterization and modulation of human mesenchymal stem cell stress pathway response following hypothermic storage. Cryobiology 2014; 68:215-26. [PMID: 24508650 DOI: 10.1016/j.cryobiol.2014.01.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 01/27/2014] [Accepted: 01/28/2014] [Indexed: 02/04/2023]
Abstract
Human mesenchymal stem cell (hMSC) research has grown exponentially in the last decade. The ability to process and preserve these cells is vital to their use in stem cell therapy. As such, understanding the complex, molecular-based stress responses associated with biopreservation is necessary to improve outcomes and maintain the unique stem cell properties specific to hMSC. In this study hMSC were exposed to cold storage (4°C) for varying intervals in three different media. The addition of resveratrol or salubrinal was studied to determine if either could improve cell tolerance to cold. A rapid elevation in apoptosis at 1h post-storage as well as increased levels of necrosis through the 24h of recovery was noted in samples. The addition of resveratrol resulted in significant improvements to hMSC survival while the addition of salubrinal revealed a differential response based on the media utilized. Decreases in both apoptosis and necrosis together with decreased cell stress/death signaling protein levels were observed following modulation. Further, ER stress and subsequent unfolded protein response (UPR) stress pathway activation was implicated in response to hMSC hypothermic storage. This study is an important first step in understanding hMSC stress responses to cold exposure and demonstrates the impact of targeted molecular modulation of specific stress pathways on cold tolerance thereby yielding improved outcomes. Continued research is necessary to further elucidate the molecular mechanisms involved in hypothermic-induced hMSC cell death. This study has demonstrated the potential for improving hMSC processing and storage through targeting select cell stress pathways.
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Affiliation(s)
- William L Corwin
- CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States.
| | - John M Baust
- CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States
| | - John G Baust
- Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States; Department of Biological Sciences, Binghamton University, Binghamton, NY 13902, United States
| | - Robert G Van Buskirk
- CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States; Department of Biological Sciences, Binghamton University, Binghamton, NY 13902, United States
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9
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Le Dinh H, de Roover A, Kaba A, Lauwick S, Joris J, Delwaide J, Honoré P, Meurisse M, Detry O. Donation after cardio-circulatory death liver transplantation. World J Gastroenterol 2012; 18:4491-506. [PMID: 22969222 PMCID: PMC3435774 DOI: 10.3748/wjg.v18.i33.4491] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2011] [Revised: 03/27/2012] [Accepted: 03/29/2012] [Indexed: 02/06/2023] Open
Abstract
The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.
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Mosbah IB, Zaouali MA, Martel C, Bjaoui M, Abdennebi HB, Hotter G, Brenner C, Roselló-Catafau J. IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation. Cell Death Dis 2012; 3:e279. [PMID: 22402603 PMCID: PMC3317344 DOI: 10.1038/cddis.2012.12] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Revised: 12/29/2011] [Accepted: 01/30/2012] [Indexed: 01/11/2023]
Abstract
Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality.
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Affiliation(s)
- I B Mosbah
- Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain
| | - M A Zaouali
- Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain
| | - C Martel
- INSERM UMR-S 769, LabEx LERMIT, Université de Paris Sud, Faculté de Pharmacie, Châtenay-Malabry 92296, France
| | - M Bjaoui
- Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain
- Department of Pharmacy, Laboratory of Human Physiology, University of Monastir, Avenue Ali Bourguiba – Skanes, BP 56, Monastir 5000, Tunisia
| | - H B Abdennebi
- Department of Pharmacy, Laboratory of Human Physiology, University of Monastir, Avenue Ali Bourguiba – Skanes, BP 56, Monastir 5000, Tunisia
| | - G Hotter
- Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain
| | - C Brenner
- INSERM UMR-S 769, LabEx LERMIT, Université de Paris Sud, Faculté de Pharmacie, Châtenay-Malabry 92296, France
| | - J Roselló-Catafau
- Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain
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11
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Minor T, Koetting M, Koetting M, Kaiser G, Efferz P, Lüer B, Paul A. Hypothermic reconditioning by gaseous oxygen improves survival after liver transplantation in the pig. Am J Transplant 2011; 11:2627-34. [PMID: 21906256 DOI: 10.1111/j.1600-6143.2011.03731.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The quality of cold-stored livers declines with the extension of ischemic time and the risk of primary dys- or nonfunction increases. Here, we provide in vivo evidence for the efficacy of the previously developed end-ischemic gaseous oxygen persufflation technique to resuscitate liver grafts after extended storage times. Porcine livers were recovered according to standard multiorgan procurement protocol. Control livers were cold stored in histidine tryptophan ketoglutarate solution for 10 h (cold storage [CS]; n = 6) at 4°C. In the treatment group (n = 6), livers were additionally subjected to hypothermic reconditioning (HR) by gaseous oxygen persufflation via the caval vein for 2 h before transplantation. Viability was assessed by orthotopic liver transplantation and 1 week follow-up. HR significantly improved pretransplant energy charge and initial graft function after transplantation. One week survival after CS was 0% whereas five of six pigs (83%) survived in the HR group. At that time, coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts. Molecular analyses identify the prevention of ischemia-induced decline of cellular autophagy and mitigation of innate immune machinery (high-mobility group protein B1, interferon-β) as operative mechanisms among the protective effects provided by HR.
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Affiliation(s)
- T Minor
- Surgical Research Division, University Clinic of Surgery, Bonn, Germany.
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12
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Guibert EE, Petrenko AY, Balaban CL, Somov AY, Rodriguez JV, Fuller BJ. Organ Preservation: Current Concepts and New Strategies for the Next Decade. Transfus Med Hemother 2011; 38:125-142. [PMID: 21566713 PMCID: PMC3088735 DOI: 10.1159/000327033] [Citation(s) in RCA: 206] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2011] [Accepted: 01/26/2011] [Indexed: 12/12/2022] Open
Abstract
SUMMARY: Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.
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Affiliation(s)
- Edgardo E. Guibert
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Alexander Y. Petrenko
- Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine, Ukraine Academy of Sciences, Kharkov, Ukraine
| | - Cecilia L. Balaban
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Alexander Y. Somov
- Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine, Ukraine Academy of Sciences, Kharkov, Ukraine
| | - Joaquín V. Rodriguez
- Centro Binacional (Argentina-Italia) de Investigaciones en Criobiología Clínica y Aplicada (CAIC), Universidad Nacional de Rosario, Argentina
| | - Barry J. Fuller
- Cell, Tissue and Organ Preservation Unit, Department of Surgery & Liver Transplant Unit, UCL Medical School, Royal Free Hospital Campus, London, UK
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13
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Manekeller S, Seinsche A, Stegemann J, Hirner A. Optimising post-conditioning time of marginal donor livers. Langenbecks Arch Surg 2008; 393:311-6. [PMID: 18283484 DOI: 10.1007/s00423-008-0288-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2008] [Accepted: 01/17/2008] [Indexed: 01/14/2023]
Abstract
BACKGROUND Due to the discrepancy between organ donors and receptors, the use of marginal livers (e.g., non-heart-beating-donor grafts) for transplantation purpose increased. The potential of a short-term aerobic machine perfusion (post-conditioning) for "less than optimal" grafts after cold storage (CS) was recently demonstrated. In our study, the optimal time course of post-conditioning (PC) is to be evaluated. MATERIALS AND METHODS Livers from male Wistar rats were withdrawn 30 min after cardiac arrest and flushed with histidine tryptophan ketoglutarate (HTK) solution. Then they were stored in HTK at 4 degrees C for 18 h. After 16 h, some livers were put on PC by cold perfusion with HTK for 0.5, 1, 2 or 3 h. Afterwards, the viability of the organs was estimated by warm reperfusion (2 h) in vitro. RESULTS After 1 h of PC, a significant increase in bile production and a decrease in enzyme release could be detected in comparison to CS. The adenosine triphosphate content of the PC livers after 1 h of treatment was significant higher than in CS organs. No markers for apoptosis could be detected after 1 h PC. CONCLUSION It can be concluded that a PC of 1 h after cold storage can ameliorate the organ viability of marginal livers. The extension or abbreviation of PC time seems to have no further beneficial effects.
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Affiliation(s)
- Steffen Manekeller
- Department of Surgery, Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
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