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Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.

Publication ,  Journal Article
Abraham, N; Zhang, M; Cray, P; Gao, Q; Samy, KP; Neill, R; Cywinska, G; Migaly, J; Kahan, R; Pontula, A; Halpern, SE; Rush, C; Penaflor, J ...
Published in: Front Med (Lausanne)
2022

BACKGROUND: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP. METHODS: To test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology. RESULTS: All point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030). CONCLUSION: Together, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation.

Duke Scholars

Published In

Front Med (Lausanne)

DOI

ISSN

2296-858X

Publication Date

2022

Volume

9

Start / End Page

804834

Location

Switzerland

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Abraham, N., Zhang, M., Cray, P., Gao, Q., Samy, K. P., Neill, R., … Barbas, A. S. (2022). Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model. Front Med (Lausanne), 9, 804834. https://doi.org/10.3389/fmed.2022.804834
Abraham, Nader, Min Zhang, Paul Cray, Qimeng Gao, Kannan P. Samy, Ryan Neill, Greta Cywinska, et al. “Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.Front Med (Lausanne) 9 (2022): 804834. https://doi.org/10.3389/fmed.2022.804834.
Abraham N, Zhang M, Cray P, Gao Q, Samy KP, Neill R, et al. Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model. Front Med (Lausanne). 2022;9:804834.
Abraham, Nader, et al. “Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.Front Med (Lausanne), vol. 9, 2022, p. 804834. Pubmed, doi:10.3389/fmed.2022.804834.
Abraham N, Zhang M, Cray P, Gao Q, Samy KP, Neill R, Cywinska G, Migaly J, Kahan R, Pontula A, Halpern SE, Rush C, Penaflor J, Kesseli SJ, Krischak M, Song M, Hartwig MG, Pollara JJ, Barbas AS. Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model. Front Med (Lausanne). 2022;9:804834.

Published In

Front Med (Lausanne)

DOI

ISSN

2296-858X

Publication Date

2022

Volume

9

Start / End Page

804834

Location

Switzerland

Related Subject Headings

  • 42 Health sciences
  • 32 Biomedical and clinical sciences