Prolonged Normothermic Machine Perfusion: Buying More Time for Liver Graft Assessment and Repair

Groen, Piet C. de; Jonge, Jeroen de; Porte, Robert J.

doi:10.1097/tp.0000000000004553

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…However, as of today no liver treated by a defatting protocol has been transplanted and toxicity of some compounds of the defatting cocktail may limit the application of this approach on the clinical setting. Despite being complicated by important technical hurdles [ 208 , 209 ], long-term NMP might be necessary to allow for effective defatting and the comprehensive viability assessment of fatty liver grafts [ 163 , 164 , 165 ].…”

Section: Normothermic Machine Perfusionmentioning

confidence: 99%

How to Preserve Steatotic Liver Grafts for Transplantation

Patrono

Stefano

Vissio

et al. 2023

JCM

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Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.

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Section: Normothermic Machine Perfusionmentioning

confidence: 99%

How to Preserve Steatotic Liver Grafts for Transplantation

Patrono

Stefano

Vissio

et al. 2023

JCM

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“…In addition to the tremendous logistic advantages 6 , an extension of perfusion time could provide an adequate time-window for more efficient marginal organ recovery. In fact, the efficacy of any reconditioning strategy, based on either pharmacological interventions 9 or endogenous resolution/repair mechanisms 10 , depends on an adequate perfusion time. Prolonged perfusion appears particularly promising in the context of NMP, where the physiological temperature allows full activation of the biological processes required to boost repair/regeneration 10 – 12 and to modulate the liver immunological function 13 .…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the efficacy of any reconditioning strategy, based on either pharmacological interventions 9 or endogenous resolution/repair mechanisms 10 , depends on an adequate perfusion time. Prolonged perfusion appears particularly promising in the context of NMP, where the physiological temperature allows full activation of the biological processes required to boost repair/regeneration 10 – 12 and to modulate the liver immunological function 13 . However, extended MP under normothermic conditions requires many crucial issues to be addressed, including adequate supply of fresh nutritional factors to hepatocytes, optimization of perfusion parameters, and identification of effective strategies for optimal oxygen delivery.…”

Section: Introductionmentioning

confidence: 99%

Twelve-hour normothermic liver perfusion in a rat model: characterization of the changes in the ex-situ bio-molecular phenotype and metabolism

Dondossola,

Lonati,

Battistin

et al. 2024

Sci Rep

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The partial understanding of the biological events that occur during normothermic machine perfusion (NMP) and particularly during prolonged perfusion might hinder its deployment in clinical transplantation. The aim of our study was to implement a rat model of prolonged NMP to characterize the bio-molecular phenotype and metabolism of the perfused organs. Livers (n = 5/group) were procured and underwent 4 h (NMP4h) or 12 h (NMP12h) NMP, respectively, using a perfusion fluid supplemented with an acellular oxygen carrier. Organs that were not exposed to any procedure served as controls (Native). All perfused organs met clinically derived viability criteria at the end of NMP. Factors related to stress-response and survival were increased after prolonged perfusion. No signs of oxidative damage were detected in both NMP groups. Evaluation of metabolite profiles showed preserved mitochondrial function, activation of Cori cycle, induction of lipolysis, acetogenesis and ketogenesis in livers exposed to 12 h-NMP. Increased concentrations of metabolites involved in glycogen synthesis, glucuronidation, bile acid conjugation, and antioxidant response were likewise observed. In conclusion, our NMP12h model was able to sustain liver viability and function, thereby deeply changing cell homeostasis to maintain a newly developed equilibrium. Our findings provide valuable information for the implementation of optimized protocols for prolonged NMP.

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“…In addition to the tremendous logistic advantages 6 , an extension of perfusion time could provide an adequate timewindow for more e cient marginal organ recovery. In fact, the e cacy of any reconditioning strategy, based on either pharmacological interventions 9 or endogenous resolution/repair mechanisms 10 , depends on an adequate perfusion time. Prolonged perfusion appears particularly promising in the context of NMP, where the physiological temperature allows full activation of the biological processes required to boost repair/regeneration [10][11][12] and to modulate the liver immunological function 13 .…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the e cacy of any reconditioning strategy, based on either pharmacological interventions 9 or endogenous resolution/repair mechanisms 10 , depends on an adequate perfusion time. Prolonged perfusion appears particularly promising in the context of NMP, where the physiological temperature allows full activation of the biological processes required to boost repair/regeneration [10][11][12] and to modulate the liver immunological function 13 . However, extended MP under normothermic conditions requires many crucial issues to be addressed, including adequate supply of fresh nutritional factors to hepatocytes, optimization of perfusion parameters, and identi cation of effective strategies for optimal oxygen delivery.…”

Section: Introductionmentioning

confidence: 99%

Twelve-hour Normothermic Liver Perfusion in a Rat Model: Characterization of the Changes in the Ex-situ Bio-molecular Phenotype and Metabolism

Daniele,

Caterina,

Michele

et al. 2023

Preprint

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The partial understanding of the biological events that occur during normothermic machine perfusion (NMP) and particularly during prolonged perfusion might hinder its deployment in clinical transplantation. The aim of our study was to implement a rat model of prolonged NMP to characterize the bio-molecular phenotype and metabolism of the perfused organs. Livers (n=5/group) were procured and underwent 4h (NMP4h) or 12h (NMP12h) NMP, respectively, using a perfusion fluid supplemented with an acellular oxygen carrier. Organs that were not exposed to any procedure served as controls (Native). All perfused organs met clinically derived viability criteria at the end of NMP. Factors related to stress-response and survival were increased after prolonged perfusion. No signs of oxidative damage were detected in both NMP groups. Evaluation of metabolite profiles showed preserved mitochondrial function, activation of Cori cycle, induction of lipolysis, acetogenesis and ketogenesis in livers exposed to 12h-NMP. Increased concentrations of metabolites involved in glycogen synthesis, glucuronidation, bile acid conjugation, and antioxidant response were likewise observed. In conclusion, our NMP12h model was able to sustain liver viability and function, thereby deeply changing cell homeostasis to maintain a newly developed equilibrium. Our findings provide valuable information for the implementation of optimized protocols for prolonged NMP.

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Prolonged Normothermic Machine Perfusion: Buying More Time for Liver Graft Assessment and Repair

Cited by 7 publications

References 9 publications

How to Preserve Steatotic Liver Grafts for Transplantation

How to Preserve Steatotic Liver Grafts for Transplantation

Twelve-hour normothermic liver perfusion in a rat model: characterization of the changes in the ex-situ bio-molecular phenotype and metabolism

Twelve-hour Normothermic Liver Perfusion in a Rat Model: Characterization of the Changes in the Ex-situ Bio-molecular Phenotype and Metabolism

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