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Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

Chinese Journal of Traumatology 2024年第2期27卷 114-120页

作者： Sheng-Feng Chen Bo-Yao Yang Tie-Yuan Zhang Xiang-Yu Song Zhi-Bo Jia Lei-Jia Chen Meng-Yi Cui Wen-Jing Xu Jiang Peng Guizhou Medical University Guiyang550025China Medical School of PLA Beijing100048 China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLADepartment of OrthopedicsThe Fourth Medical CenterChinese PLA General HospitalBeijing100048China Hebei North Universiy Zhangjiakou075000Hebei ProvinceChina

Purpose:Ischemia and hypoxia are the main factors limiting limb replantation and transplantation.Static cold storage(SCS),a common preservation method for tissues and organs,can only prolong limb ischemia time to 4-6 h.The normothermic machine perfusion(NMP)is a promising method for the preservation of tissues and organs,which can extend the preservation time in vitro by providing continuous oxygen and nutrients.This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods.Methods:The 6 forelimbs from beagle dogs were divided into 2 groups.In the SCS group(n=3),the limbs were preserved in a sterile refrigerator at 4°C for 24 h,and in the NMP group(n=3),the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h,and the solution was changed every 6 h.The effects of limb storage were evaluated by weight gain,perfusate biochemical analysis,enzyme-linked immunosorbent assay,and histological analysis.All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance.The p value of less than 0.05 was considered to indicate statistical significance.Results:In the NMP group,the weight gained percentage was 11.72%±4.06%;the hypoxia-inducible factor-1αcontents showed no significant changes;the shape of muscle fibers was normal;the gap between muscle fibers slightly increased,showing the intercellular distance of(30.19±2.83)μm;and the vascularα-smooth muscle actin(α-SMA)contents were lower than those in the normal blood vessels.The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion,decreased after each perfusate change,and remained stable at the end of perfusion showing a peak level of 4097.6 U/L.The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L.In the SCS group,the percentage of weight gain was 0.18%±0.10%,and the contents of hypoxia-inducible factor-1αin

关键词： Traumatic amputation machine perfusion Static cold storage Limb replantation

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Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

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World Journal of Gastroenterology 2024年第11期30卷 1488-1493页

作者： Alessandro Parente Keyue Sun Philipp Dutkowski AM James Shapiro Andrea Schlegel Department of Surgery Division of TransplantationUniversity of Alberta HospitalEdmonton T6G 2B7Canada Immunity and Inflammation Lerner Research InstituteClevelandOH 44195United States Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryUniversity Hospital ZurichZurich 8091Switzerland Immunity and Inflammation Digestive Disease and Surgery InstituteClevelandOH 44195United States

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

关键词： Liver transplantation machine perfusion Viability assessment Hypothermic oxygenated perfusion Normothermic machine perfusion

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Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond

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World Journal of Gastroenterology 2022年第48期28卷 6922-6934页

作者： Bianca Della Guardia Amanda P C S Boteon Celso E L Matielo Guilherme Felga Yuri L Boteon Liver Unit Hospital Israelita Albert EinsteinSão Paulo 05652-900Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein Faculdade Israelita de Ciências da Saúde Albert EinsteinSão Paulo 05652-900Brazil

Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

关键词： Acute-on-chronic liver failure Liver cirrhosis Liver transplantation machine perfusion Hypothermic oxygenated machine perfusion

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machine perfusion versus cold storage of livers： a meta-analysis

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Frontiers of Medicine 2016年第4期10卷 451-464页

作者： Sushun Liu Qing Pang Jingyao Zhang Mimi Zhai Sinan Liu Chang Liu Department of Hepatobiliary Surgery The First Affiliated Hospital School of Medicine Xi 'an Jiaotong University Xi 'an 710061 China

Abstract Different organ preservation methods are key factors influencing the results of fiver transplantation. In this study, the outcomes of experimental models receiving donation after cardiac death （DCD） livers preserved through machine perfusion （MP） or static cold storage （CS） were compared by conducting a meta-analysis. Standardized mean difference （SMD） and 95% confidence interval （CI） were calculated to compare pooled data from two animal species. Twenty-four studies involving MP preservation were included in the meta-analysis. Compared with CS preservation, MP can reduce the levels of aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, lactate dehydrogenase （LDH）, and hyaluronic acid （HA） and the changes in liver weight. By contrast, MP can enhance bile production and portal vein flow （PVF）. Alkaline phosphatase （ALP） levels and histological changes significantly differed between the two preservation methods. In conclusion, MP of DCD livers is superior to CS in experimental animals.

关键词： machine perfusion cold storage DCD meta-analysis

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machine perfusion for liver transplantation:A concise review of clinical trials

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 387-391页

作者： Jun-Jun Jia Jian-Hui Li Hao Yu Yu Nie Li Jiang Hao-Yu Li Lin Zhou Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Combined Multi-organ Transplantation Ministry of Public HealthHangzhou 310003China Collaborative Innovation Centers for Diagnosis Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.

关键词： Liver transplantation machine perfusion Donation after circulatory death

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machine perfusion in abdominal organ transplantation: Current use in the Netherlands

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World Journal of Transplantation 2020年第1期10卷 15-28页

作者： Elsaline Rijkse Jan NM IJzermans Robert C Minnee Division of HPB and Transplant Surgery Department of Surgery Erasmus MC University Medical Center

Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor organs,there is an increased interest in better preservation methods,such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes.This state-ofthe-art review aims to discuss the available types of perfusion techniques,its potential benefits and the available evidence in kidney,liver and pancreas transplantation.Additionally,translational steps from animal models towards clinical studies will be described,as well as its application to clinical practice,with the focus on the Netherlands.Despite the lack of evidence from randomized controlled trials,currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation.For ex vivo machine perfusion in kidney transplantation,hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial,while normothermic machine perfusion is currently under investigation.For ex vivo machine perfusion in liver transplantation,normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction.In response to clinical studies,hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.

关键词： machine perfusion Review Kidney transplantation Liver transplantation Pancreas transplantation

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Cold ischemia time in liver transplantation:An overview

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World Journal of Hepatology 2024年第6期16卷 883-890页

作者： Manuela Cesaretti Alessandro Izzo Roberta Anna Pellegrino Alessandro Galli Orestes Mavrothalassitis Department of HPB and Liver Transplantation Brotzu HospitalCagliari 09122Italy Department of Nanophysic Istituto Italiano di TecnologiaGenova 16163Italy Department of Critical Care Medicine and Anesthesia ASST Papa Giovanni XXIIIBergamo 24100Italy Department of Anesthesia and Perioperative Care University of California San FranciscoSan FranciscoCA 94143United States

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time(CIT).This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time,transit time,and recipient surgery time,and is one of the most important donor-related risk factors which may influence the graft and recipient’s survival.Recently,the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies.This review details the CIT definition and analyzes its different factors.It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

关键词： Cold ischemia time Liver transplantation Organ donation Donation after cardiac death Warm ischemia time machine perfusion

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Concise review of machine perfusion in liver transplantation

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World Journal of Hepatology 2020年第1期12卷 6-9页

作者： Chirag S Desai David A Gerber Department of Surgery University of North Carolina at Chapel HillChapel HillNC 27599United States Lineberger Cancer Center University of North Carolina at Chapel HillChapel HillNC 27599United States

With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.

关键词： Liver transplantation machine perfusion Ex vivo perfusion Ischemia reperfusion Organ preservation

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Liver transplantation for malignant liver tumors

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iLIVER 2022年第1期1卷 3-11页

作者： Richard X.Sousa Da Silva Beat Muellhaupt Philipp Dutkowski Pierre-Alain Clavien Department of Surgery and Transplantation Swiss Hepato-Pancreato-Biliary(HPB)and Transplant CenterUniversity Hospital ZurichRaemistrasse 1008091 ZurichSwitzerland Wyss Zurich ETH ZurichUniversity of ZurichWeinbergstrasse 358006 ZurichSwitzerland Department of Gastroenterology and Hepatology University Hospital ZurichRaemistrasse 1008091 ZurichSwitzerland

Liver transplantation is a highly effective treatment not only for acute or chronic liver failure but also for primary liver cancer such as hepatocellular carcinoma,perihilar cholangiocarcinoma,intrahepatic cholangiocarcinoma,and metastatic tumors such as from neuroendocrine or colorectal liver metastases.The success strongly relies on strict adherence to stringent selection criteria,which lead to excellent outcomes,while previously regarded as contraindication for liver transplantation.These impressive results are,however,mostly achieved with a combination of pretreatment strategies and convincing control of the tumor growth prior to transplantation,as well as minimizing long-term immunosuppression.With this emergence of oncologic liver transplantation,we expect an increasing need of grafts,and therefore included in this report strategies to improve the number of available grafts by maximizing liver utilization rates.Modern machine liver perfusion approaches may play in this respect an important role.

关键词： Liver transplantation Selection criteria Malignant tumor machine perfusion Tumor recurrence

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