The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
P J Friend - One of the best experts on this subject based on the ideXlab platform.
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design analysis and pitfalls of clinical trials using ex situ Liver machine Perfusion the international Liver transplantation society consensus guidelines
Transplantation, 2021Co-Authors: Paulo N Martins, P J Friend, Michael Rizzari, Davide Ghinolfi, Ina Jochmans, M Attia, Rajiv Jalan, Machine PerfusionAbstract:Background Recent trials in Liver machine Perfusion (MP) have revealed unique challenges beyond those seen in most clinical studies. Correct trial design and interpretation of data are essential to avoid drawing conclusions that may compromise patient safety and increase costs. Methods The International Liver Transplantation Society, through the Special Interest Group "DCD, Preservation and Machine Perfusion," established a working group to write consensus statements and guidelines on how future clinical trials in Liver Perfusion should be designed, with particular focus on relevant clinical endpoints and how different techniques of Liver Perfusion should be compared. Protocols, abstracts, and full published papers of clinical trials using Liver MP were reviewed. The use of a simplified Grading of Recommendations Assessment, Development, and Evaluation working group (GRADE) system was attempted to assess the level of evidence. The working group presented its conclusions at the International Liver Transplantation Society consensus conference "DCD, Liver Preservation, and Machine Perfusion" held in Venice, Italy, on January 31, 2020. Results Twelve recommendations were proposed with the main conclusions that clinical trials investigating the effect of MP in Liver transplantation should (1) make the protocol publicly available before the start of the trial, (2) be adequately powered, and (3) carefully consider timing of randomization in function of the primary outcome. Conclusions There are issues with using accepted primary outcomes of Liver transplantation trials in the context of MP trials, and no ideal endpoint could be defined by the working group. The setup of an international registry was considered vital by the working group.
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a back to base experience of human normothermic ex situ Liver Perfusion does the chill kill
Liver Transplantation, 2019Co-Authors: Mariusz Bral, David L. Bigam, P J Friend, Khaled Dajani, Dayne Leon Izquierdo, Norman M Kneteman, Carlo D L Ceresa, A. James M. ShapiroAbstract:Normothermic machine Perfusion (NMP) has been shown to protect Livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back-to-base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back-to-base Livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30-day patient and graft survival. A total of 46 Liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ Perfusion function. The 30-day patient and graft survival in the back-to-base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back-to-base Livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back-to-base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.
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ex vivo normothermic Liver Perfusion an update
Current Opinion in Organ Transplantation, 2010Co-Authors: Thomas Vogel, Jens Brockmann, P J FriendAbstract:Purpose of reviewThere is increasing disparity between the supply of acceptable donor organs and the number of potential transplant recipients. The shortage of organs for transplantation demands optimal utilization of a wider spectrum of donor organs, including nonheart-beating and other extended cr
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classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine Liver Perfusion
Transplantation, 2004Co-Authors: Michael Rees, Andrew J Butler, Margaret C Negus, Hugh F S Davies, P J FriendAbstract:Background. Porcine Livers perfused with human blood destroy 85% of human erythrocytes (red blood cells [RBC]) during prolonged extracorporeal Perfusion, raising the possibility of a complement-mediated graft-versus-host effect. Methods. Isolated porcine Livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis and porcine immunoglobulin class and specificity by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Anti-CD59 and anti-decay accelerating factor (DAF) monoclonal antibody were used to investigate whether human complement regulatory proteins inhibit porcine complement. Results. After 64 hr of Perfusion of porcine Livers with human blood, mean complement activity in the perfusate was 95% of the starting value and increasing, whereas Perfusion in the absence of a Liver showed a falling complement activity of 28.7%. ELISA demonstrated porcine immunoglobulin (Ig) G and IgM in the xenoperfused human plasma. Whereas in a previous study flow cytometry demonstrated porcine antibodies specific for antigens on human T lymphocytes, in this study, anti-human RBC antibodies were not found. Xenoperfused human plasma did not lyse fresh human RBC. Human complement was consistently more efficient at lysing porcine RBC than was porcine complement at lysing human RBC, and human plasma inhibited the ability of porcine plasma to lyse human RBC, raising the possibility of cross-species complement regulation. Complement regulatory proteins on human RBC were blocked using mouse monoclonal anti-human CD59 and DAF. Blocking CD59, but not DAF, augmented lysis of human RBC by porcine complement. Conclusions. Human CD59 inhibits porcine complement. The production of porcine complement from xenoperfused porcine Livers is unlikely to result in clinically significant injury mediated through the classical pathway of complement activation.
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successful extracorporeal porcine Liver Perfusion for 72 hr
Transplantation, 2002Co-Authors: Andrew J Butler, Michael A Rees, Derek G D Wight, Neil D Casey, Graeme J M Alexander, D J G White, P J FriendAbstract:Background. Improvements in extracorporeal Perfusion technology and the production of transgenic pigs resistant to hyperacute rejection have stimulated several groups to re-explore the possibility of supporting patients in hepatic failure with extracorporeal porcine Livers. The success of organ transplantation has also stimulated interest in using extracorporeal Perfusion as a means of organ preservation and resuscitation of organs from marginal donors. The present study describes a method by which Livers can be maintained in a viable condition for a minimum of 72 hr of normothermic, extracorporeal Perfusion. Methods. Five extracorporeal porcine Liver Perfusions were performed, each with a duration of 72 hr. Hepatectomy was performed, followed by cold preservation, cannulation of vessels, and initiation of Perfusion with normothermic, oxygenated porcine blood. Organ viability was assessed by metabolic, synthetic, hemodynamic, and histologic parameters. Results. After 72 hr of normothermic, extracorporeal Perfusion, the isolated Livers demonstrated maintenance of normal physiological levels of pH and electrolytes. Continued hepatic protein synthesis (complement and factor V) was maintained throughout the Perfusion. Hemodynamic parameters remained within normal physiological range. Histology demonstrated good preservation of the Liver with no overall architectural change. Conclusion. It is possible to maintain a Liver in a viable condition for a minimum of 72 hr of extracorporeal Perfusion. This technique has been developed primarily as a preclinical model of extracorporeal Liver support with the intention of proceeding to a clinical trial in patients with fulminant Liver failure. However, it also has potential applications in organ preservation or resuscitation before transplantation and in the experimental study of isolated Liver physiology.
Andrew J Butler - One of the best experts on this subject based on the ideXlab platform.
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normothermic Perfusion in the assessment and preservation of declined Livers before transplantation hyperoxia and vasoplegia important lessons from the first 12 cases
Transplantation, 2017Co-Authors: Christopher J E Watson, Vasilis Kosmoliaptsis, Lucy V Randle, A E S Gimson, Rebecca Brais, John R Klinck, Mazin Hamed, Anastasia Tsyben, Andrew J ButlerAbstract:BackgroundA program of normothermic ex situ Liver Perfusion (NESLiP) was developed to facilitate better assessment and use of marginal Livers, while minimizing cold ischemia.MethodsDeclined marginal Livers and those offered for research were evaluated. Normothermic ex situ Liver Perfusion was perfor
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preimplant normothermic Liver Perfusion of a suboptimal Liver donated after circulatory death
American Journal of Transplantation, 2016Co-Authors: Christopher J E Watson, Vasilis Kosmoliaptsis, Lucy V Randle, Neil Russell, W J H Griffiths, Scott P Davies, Hynek Mergental, Andrew J ButlerAbstract:Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of preimplant normothermic Perfusion of a suboptimal Liver from a 57-year-old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life-supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the Liver was subject to normothermic machine Perfusion with a plasma-free red cell-based perfusate. Perfusate lactate level fell from 7.2 to 0.3 mmol/L within 74 minutes of ex situ Perfusion, at which point perfusate alanine transaminase level was 1152 IU/L and urea concentration was 9.4 mmol/L. After 132 minutes, normothermic Perfusion was stopped and implantation begun. After transplantation, the patient made an uneventful recovery and was discharged on day 8; Liver biochemistry was normal by day 19 and has remained normal thereafter. Donor common bile duct excised at implantation showed preservation of peribiliary glands, and cholangiography 6 months posttransplantation showed no evidence of cholangiopathy. Preimplant ex situ normothermic Perfusion of the Liver appears to be a promising way to evaluate a marginal Liver before transplantation and may modify the response to ischemia.
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classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine Liver Perfusion
Transplantation, 2004Co-Authors: Michael Rees, Andrew J Butler, Margaret C Negus, Hugh F S Davies, P J FriendAbstract:Background. Porcine Livers perfused with human blood destroy 85% of human erythrocytes (red blood cells [RBC]) during prolonged extracorporeal Perfusion, raising the possibility of a complement-mediated graft-versus-host effect. Methods. Isolated porcine Livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis and porcine immunoglobulin class and specificity by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Anti-CD59 and anti-decay accelerating factor (DAF) monoclonal antibody were used to investigate whether human complement regulatory proteins inhibit porcine complement. Results. After 64 hr of Perfusion of porcine Livers with human blood, mean complement activity in the perfusate was 95% of the starting value and increasing, whereas Perfusion in the absence of a Liver showed a falling complement activity of 28.7%. ELISA demonstrated porcine immunoglobulin (Ig) G and IgM in the xenoperfused human plasma. Whereas in a previous study flow cytometry demonstrated porcine antibodies specific for antigens on human T lymphocytes, in this study, anti-human RBC antibodies were not found. Xenoperfused human plasma did not lyse fresh human RBC. Human complement was consistently more efficient at lysing porcine RBC than was porcine complement at lysing human RBC, and human plasma inhibited the ability of porcine plasma to lyse human RBC, raising the possibility of cross-species complement regulation. Complement regulatory proteins on human RBC were blocked using mouse monoclonal anti-human CD59 and DAF. Blocking CD59, but not DAF, augmented lysis of human RBC by porcine complement. Conclusions. Human CD59 inhibits porcine complement. The production of porcine complement from xenoperfused porcine Livers is unlikely to result in clinically significant injury mediated through the classical pathway of complement activation.
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successful extracorporeal porcine Liver Perfusion for 72 hr
Transplantation, 2002Co-Authors: Andrew J Butler, Michael A Rees, Derek G D Wight, Neil D Casey, Graeme J M Alexander, D J G White, P J FriendAbstract:Background. Improvements in extracorporeal Perfusion technology and the production of transgenic pigs resistant to hyperacute rejection have stimulated several groups to re-explore the possibility of supporting patients in hepatic failure with extracorporeal porcine Livers. The success of organ transplantation has also stimulated interest in using extracorporeal Perfusion as a means of organ preservation and resuscitation of organs from marginal donors. The present study describes a method by which Livers can be maintained in a viable condition for a minimum of 72 hr of normothermic, extracorporeal Perfusion. Methods. Five extracorporeal porcine Liver Perfusions were performed, each with a duration of 72 hr. Hepatectomy was performed, followed by cold preservation, cannulation of vessels, and initiation of Perfusion with normothermic, oxygenated porcine blood. Organ viability was assessed by metabolic, synthetic, hemodynamic, and histologic parameters. Results. After 72 hr of normothermic, extracorporeal Perfusion, the isolated Livers demonstrated maintenance of normal physiological levels of pH and electrolytes. Continued hepatic protein synthesis (complement and factor V) was maintained throughout the Perfusion. Hemodynamic parameters remained within normal physiological range. Histology demonstrated good preservation of the Liver with no overall architectural change. Conclusion. It is possible to maintain a Liver in a viable condition for a minimum of 72 hr of extracorporeal Perfusion. This technique has been developed primarily as a preclinical model of extracorporeal Liver support with the intention of proceeding to a clinical trial in patients with fulminant Liver failure. However, it also has potential applications in organ preservation or resuscitation before transplantation and in the experimental study of isolated Liver physiology.
A. James M. Shapiro - One of the best experts on this subject based on the ideXlab platform.
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a back to base experience of human normothermic ex situ Liver Perfusion does the chill kill
Liver Transplantation, 2019Co-Authors: Mariusz Bral, David L. Bigam, P J Friend, Khaled Dajani, Dayne Leon Izquierdo, Norman M Kneteman, Carlo D L Ceresa, A. James M. ShapiroAbstract:Normothermic machine Perfusion (NMP) has been shown to protect Livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back-to-base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back-to-base Livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30-day patient and graft survival. A total of 46 Liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ Perfusion function. The 30-day patient and graft survival in the back-to-base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back-to-base Livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back-to-base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.
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Clearance of transaminases during normothermic ex situ Liver Perfusion
2019Co-Authors: Mariusz Bral, Nader Aboelnazar, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Darren H. Freed, A. James M. ShapiroAbstract:BackgroundOne of the most promising applications of Liver normothermic machine Perfusion (NMP) is the potential to directly assess graft viability and injury. In most NMP studies, perfusate transaminases are utilized as markers of graft injury. Our aim was to further elucidate the metabolism of transaminases by healthy porcine Livers during NMP, specifically whether such Livers could clear circuit perfusate transaminases.MethodsA highly concentrated transaminase solution was prepared from homogenized Liver, with an aspartate aminotransferase (AST) level of 107,427 U/L. Three Livers in the treatment group were compared to three controls, during 48 hours of NMP. In the treatment group, the circuit perfusate was injected with the transaminase solution to artificially raise the AST level to a target of 7,500 U/L. Perfusate samples were taken at two-hour intervals and analyzed for biochemistry until NMP end. Graft oxygen consumption and vascular parameters were monitored.ResultsCompared to controls, treated Perfusions demonstrated abrupt elevations in transaminase levels (p>0.0001) and lactate dehydrogenase (LDH) (p>0.0001), which decreased over time, but never to control baseline. Liver function, as demonstrated by lactate clearance and oxygen consumption was not different between groups. The treatment group demonstrated a higher portal vein resistance (p = 0.0003), however hepatic artery resistance was similar. Treated Livers had higher bile production overall (p
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Schematic diagram of the experimental ex situ circuit.
2019Co-Authors: Mariusz Bral, Nader Aboelnazar, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Darren H. Freed, A. James M. ShapiroAbstract:In this study prostacyclin, bile salts and nutrients were omitted from the infusions. Reprinted from ‘Mariusz Bral, Boris Gala-Lopez, Aducio Thiesen, Sanaz Hatami, David L. Bigam, Darren M. Freed, AM James Shapiro, Determination of Minimal Hemoglobin Level Necessary for Normothermic Porcine Ex Situ Liver Perfusion, Transplantation. 2018;102(8):1284–1292, with permission from Transplantation.
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determination of minimal hemoglobin level necessary for normothermic porcine ex situ Liver Perfusion
Transplantation, 2018Co-Authors: Mariusz Bral, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Boris Galalopez, Darren M Freed, A. James M. ShapiroAbstract:BACKGROUND In current studies of ex situ Liver Perfusion there exists considerable variability in perfusate composition, including the type of oxygen carrier. Herein, we aim to clarify the minimal hemoglobin level necessary during normothermic porcine ex situ Liver Perfusion. METHODS Livers procured from 35 to 45 kg domestic pigs were connected to our experimental ex situ circuit (n = 10). In the treatment group, perfusate was sequentially diluted hourly to predetermined hemoglobin levels. At the end of each hemoglobin dilution, perfusate samples were analyzed for Liver transaminases, lactate dehydrogenase (LD), total bilirubin, and lactate levels. Liver oxygen consumption was measured. In the control group, Livers were perfused continually for a duration of 24 hours at target hemoglobin levels of 30 and 20 g/L. RESULTS Rising Liver transaminases, significantly higher lactate (P < 0.001), and LD levels (P < 0.001) were noted at lower perfusate hemoglobin levels in the treatment group. Liver oxygen utilization (P < 0.001) and hepatic artery oxygen deLivery (P < 0.001) were significantly lower at lower hemoglobin levels, whereas Liver vessel resistance remained relatively constant. Histology demonstrated increasing parenchymal damage at lower hemoglobin levels. In control Livers, higher perfusate transaminases, higher lactate, and LD levels were noted at a Perfusion hemoglobin level of 20 g/L. CONCLUSIONS Ex situ Liver function decompensated during Perfusion between a mean hemoglobin level of 30 to 20 g/L, as evidenced by notably rising lactate and LD levels. This study demonstrates optimal hemoglobin concentration during normothermic ex situ Liver Perfusion to ensure a fully metabolically functioning graft.
Mariusz Bral - One of the best experts on this subject based on the ideXlab platform.
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a back to base experience of human normothermic ex situ Liver Perfusion does the chill kill
Liver Transplantation, 2019Co-Authors: Mariusz Bral, David L. Bigam, P J Friend, Khaled Dajani, Dayne Leon Izquierdo, Norman M Kneteman, Carlo D L Ceresa, A. James M. ShapiroAbstract:Normothermic machine Perfusion (NMP) has been shown to protect Livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back-to-base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back-to-base Livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30-day patient and graft survival. A total of 46 Liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ Perfusion function. The 30-day patient and graft survival in the back-to-base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back-to-base Livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back-to-base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.
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Clearance of transaminases during normothermic ex situ Liver Perfusion
2019Co-Authors: Mariusz Bral, Nader Aboelnazar, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Darren H. Freed, A. James M. ShapiroAbstract:BackgroundOne of the most promising applications of Liver normothermic machine Perfusion (NMP) is the potential to directly assess graft viability and injury. In most NMP studies, perfusate transaminases are utilized as markers of graft injury. Our aim was to further elucidate the metabolism of transaminases by healthy porcine Livers during NMP, specifically whether such Livers could clear circuit perfusate transaminases.MethodsA highly concentrated transaminase solution was prepared from homogenized Liver, with an aspartate aminotransferase (AST) level of 107,427 U/L. Three Livers in the treatment group were compared to three controls, during 48 hours of NMP. In the treatment group, the circuit perfusate was injected with the transaminase solution to artificially raise the AST level to a target of 7,500 U/L. Perfusate samples were taken at two-hour intervals and analyzed for biochemistry until NMP end. Graft oxygen consumption and vascular parameters were monitored.ResultsCompared to controls, treated Perfusions demonstrated abrupt elevations in transaminase levels (p>0.0001) and lactate dehydrogenase (LDH) (p>0.0001), which decreased over time, but never to control baseline. Liver function, as demonstrated by lactate clearance and oxygen consumption was not different between groups. The treatment group demonstrated a higher portal vein resistance (p = 0.0003), however hepatic artery resistance was similar. Treated Livers had higher bile production overall (p
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Schematic diagram of the experimental ex situ circuit.
2019Co-Authors: Mariusz Bral, Nader Aboelnazar, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Darren H. Freed, A. James M. ShapiroAbstract:In this study prostacyclin, bile salts and nutrients were omitted from the infusions. Reprinted from ‘Mariusz Bral, Boris Gala-Lopez, Aducio Thiesen, Sanaz Hatami, David L. Bigam, Darren M. Freed, AM James Shapiro, Determination of Minimal Hemoglobin Level Necessary for Normothermic Porcine Ex Situ Liver Perfusion, Transplantation. 2018;102(8):1284–1292, with permission from Transplantation.
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determination of minimal hemoglobin level necessary for normothermic porcine ex situ Liver Perfusion
Transplantation, 2018Co-Authors: Mariusz Bral, Sanaz Hatami, Aducio Thiesen, David L. Bigam, Boris Galalopez, Darren M Freed, A. James M. ShapiroAbstract:BACKGROUND In current studies of ex situ Liver Perfusion there exists considerable variability in perfusate composition, including the type of oxygen carrier. Herein, we aim to clarify the minimal hemoglobin level necessary during normothermic porcine ex situ Liver Perfusion. METHODS Livers procured from 35 to 45 kg domestic pigs were connected to our experimental ex situ circuit (n = 10). In the treatment group, perfusate was sequentially diluted hourly to predetermined hemoglobin levels. At the end of each hemoglobin dilution, perfusate samples were analyzed for Liver transaminases, lactate dehydrogenase (LD), total bilirubin, and lactate levels. Liver oxygen consumption was measured. In the control group, Livers were perfused continually for a duration of 24 hours at target hemoglobin levels of 30 and 20 g/L. RESULTS Rising Liver transaminases, significantly higher lactate (P < 0.001), and LD levels (P < 0.001) were noted at lower perfusate hemoglobin levels in the treatment group. Liver oxygen utilization (P < 0.001) and hepatic artery oxygen deLivery (P < 0.001) were significantly lower at lower hemoglobin levels, whereas Liver vessel resistance remained relatively constant. Histology demonstrated increasing parenchymal damage at lower hemoglobin levels. In control Livers, higher perfusate transaminases, higher lactate, and LD levels were noted at a Perfusion hemoglobin level of 20 g/L. CONCLUSIONS Ex situ Liver function decompensated during Perfusion between a mean hemoglobin level of 30 to 20 g/L, as evidenced by notably rising lactate and LD levels. This study demonstrates optimal hemoglobin concentration during normothermic ex situ Liver Perfusion to ensure a fully metabolically functioning graft.
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preliminary single center canadian experience of human normothermic ex vivo Liver Perfusion results of a clinical trial
American Journal of Transplantation, 2017Co-Authors: Mariusz Bral, David L. Bigam, Boris Galalopez, Norman M Kneteman, Andrew J Malcolm, Scott Livingstone, Axel Andres, Juliet Emamaullee, Leslie James Russell, Constantin C CoussiosAbstract: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. Transplanted NMP grafts were matched 1:3 with transplanted SCS Livers. Median NMP was 11.5 h (range 3.3-22.5 h) with one DCD Liver perfused for 22.5 h. All transplanted Livers functioned, and serum transaminases, bilirubin, international normalized ratio, and lactate levels corrected in NMP recipients similarly to controls. Graft survival at 30 days (primary outcome) was not statistically different between groups on an intent-to-treat basis (p = 0.25). Intensive care and hospital stays were significantly more prolonged in the NMP group. This preliminary experience demonstrates feasibility as well as potential technical risks of NMP in a North American setting and highlights a need for larger, randomized studies.
Philipp Dutkowski - One of the best experts on this subject based on the ideXlab platform.
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hypothermic machine preservation of the Liver state of the art
Current Transplantation Reports, 2018Co-Authors: A. Schlegel, Xavier Muller, Philipp DutkowskiAbstract: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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role of hypothermic machine Perfusion in Liver transplantation
Transplant International, 2015Co-Authors: A. Schlegel, Philipp DutkowskiAbstract:Abstract Machine Liver Perfusion has significantly evolved during the last ten years to optimize extended criteria Liver grafts and to address the worldwide organ shortage. This review gives an overview on available ex vivo and in vivo data on hypothermic machine Liver Perfusion. We discuss also possible protective pathways and show most recent clinical applications of hypothermic machine Liver Perfusion in human.
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Machine Perfusion for ‘Marginal’ Liver Grafts
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2008Co-Authors: Philipp Dutkowski, O. De Rougemont, Pierre-alain ClavienAbstract:Due to the critical shortage of deceased donor grafts, clinicians are continually expanding the criteria for an acceptable Liver donor to meet the waiting list demands. However, the reduced ischemic tolerance of those extended criteria grafts jeopardizes organ viability during cold storage. Machine Perfusion has been developed to limit ischemic Liver damage but despite its proven biochemical benefit, machine Liver Perfusion is not yet considered clinically due to its low practicability. In this review, we summarize our understanding of the role of machine Perfusion in marginal Liver preservation. The goal is to highlight advantages or disadvantages of current Perfusion techniques and to explain the underlying mechanisms. We provide evidence for the need of a Liver Perfusion performance shortly before implantation, and point out promising designs.
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novel short term hypothermic oxygenated Perfusion hope system prevents injury in rat Liver graft from non heart beating donor
Annals of Surgery, 2006Co-Authors: Philipp Dutkowski, Katarzyna Furrer, Yinghua Tian, Rolf Graf, Pierre-alain ClavienAbstract:Objective: To assess a machine Perfusion system in rescuing Liver grafts from non-heart-beating donors (NHBD). Background Data: The introduction of extracorporeal Liver Perfusion systems in the clinical routine depends on feasibility. Conceivably, Perfusion could be performed during recipient preparation. We investigated whether a novel rat Liver machine Perfusion applied after in situ ischemia and cold storage can rescue NHBD Liver grafts. Methods: We induced cardiac arrest in male Brown Norway rats by phrenotomy and ligation of the subcardial aorta. We studied 2 experimental groups: 45 minutes of warm in situ ischemia + 5 hours cold storage versus 45 minutes of warm in situ ischemia + 5 hours cold storage followed by 1 hour hypothermic oxygenated extracorporeal Perfusion (HOPE). In both groups, Livers were reperfused in a closed sanguineous isolated Liver Perfusion device for 3 hours at 37°C. To test the benefit of HOPE on survival, we performed orthotopic Liver transplantation in both experimental groups. Results: After cold storage and rePerfusion, NHBD Livers showed necrosis of hepatocytes, increased release of AST, and decreased bile flow. HOPE improved NHBD Livers significantly with a reduction of necrosis, less AST release, and increased bile flow. ATP was severely depleted in cold-stored NHBD Livers but restored in Livers treated by HOPE. After orthotopic Liver transplantation, grafts treated by HOPE demonstrated a significant extension on animal survival. Conclusions: We demonstrate a beneficial effect of HOPE by preventing rePerfusion injury in a clinically relevant NHBD model.