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Updated: Jul 30, 2026
Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts
Published on: August 13, 2014
Dynamics of Ischemia/Reperfusion Injury Markers During Normothermic Liver Machine Perfusion
Aránzazu Caballero-Marcos1,2, Luis Rodríguez-Bachiller3, Alberto Baroja-Mazo4
1Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Background:
A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated.
Methods:
Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate.
Results:
Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 (P = 0.001), intercellular adhesion molecule 1 (P = 0.01), and urokinase plasminogen activator (P = 0.001).
Conclusions:
Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology.
Insights
This study found that lactate levels in liver perfusate correlate with ischemia/reperfusion injury (IRI) mechanisms during normothermic machine perfusion (NMP). Accumulating IRI biomarkers during NMP may limit its benefits for liver viability assessment.
Area of Science:
- Transplantation
- Organ Preservation
- Biomarker Discovery
Background:
- Normothermic machine perfusion (NMP) is crucial for assessing liver viability, but a complete mechanistic understanding is needed.
- While inflammation markers in NMP are studied, other ischemia/reperfusion injury (IRI) mechanisms require evaluation.
- Identifying reliable biomarkers is essential to optimize NMP protocols and improve organ outcomes.
Purpose of the Study:
- To comprehensively assess IRI mechanisms during NMP in human donor livers.
- To identify and quantify specific biomarkers in perfusate that indicate liver injury.
- To explore correlations between perfusate biomarkers and underlying pathological processes.
Main Methods:
- Eight human donor livers were preserved using NMP.
- Perfusate samples were collected throughout the NMP period.
- Concentrations of various IRI-related biomarkers were measured.
Main Results:
- Levels of adhesion molecules (ICAM-1, P-selectin, VCAM-1), MMP-13, PLA2G7, and syndecan-1 increased during NMP.
- Perfusate lactate showed significant correlations with CXCL10, ICAM-1, and uPA.
- Lactate levels in perfusate reflect key biological processes occurring during NMP.
Conclusions:
- Perfusate lactate is a potential indicator of underlying biological mechanisms in NMP.
- The accumulation of IRI biomarkers during NMP may pose limitations to its efficacy.
- Further research is needed to validate these biomarkers for liver viability assessment.
