Clearance of transaminases during normothermic ex situ liver perfusion

One 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...

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Bibliographic Details
Published in:PloS one 2019-04, Vol.14 (4), p.e0215619-e0215619
Main Authors: Bral, Mariusz, Aboelnazar, Nader, Hatami, Sanaz, Thiesen, Aducio, Bigam, David L, Freed, Darren H, Shapiro, A M James
Format: Article
Language:English
Subjects:
Animals
Aspartate
Aspartate aminotransferase
Bile
Biochemistry
Biomarkers - metabolism
Care and treatment
Coronary vessels
Diagnosis
Enzymes
Grafting
Hepatic artery
Hepatology
Humans
Immunological tolerance
In Vitro Techniques
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Liver
Liver - anatomy & histology
Liver - metabolism
Liver - physiology
Liver diseases
Liver Function Tests - methods
Liver Transplantation - methods
Liver transplants
Metabolic Clearance Rate
Metabolism
Models, Animal
Organ Preservation - instrumentation
Organ Preservation - methods
Oxygen
Oxygen Consumption
Perfusion
Perfusion - instrumentation
Perfusion - methods
Portal vein
Portal Vein - physiology
Surgery
Sus scrofa
Temperature
Transaminase
Transaminases
Transaminases - metabolism
Transplants & implants
Vascular Resistance
Viability
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Summary:One 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. A 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. Compared 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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0215619