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Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions

We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions (21°C) with a new hemoglobin‐based oxygen carrier (HBOC) solution. MP (n = 6) was compared to cold static preservation (CSP; n = 6) in porcine orthotopic liver transplants after 9 h of cold ischemi...

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Autores principales: Fontes, P., Lopez, R., van der Plaats, A., Vodovotz, Y., Minervini, M., Scott, V., Soltys, K., Shiva, S., Paranjpe, S., Sadowsky, D., Barclay, D., Zamora, R., Stolz, D., Demetris, A., Michalopoulos, G., Marsh, J. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024042/
https://www.ncbi.nlm.nih.gov/pubmed/25612645
http://dx.doi.org/10.1111/ajt.12991
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author Fontes, P.
Lopez, R.
van der Plaats, A.
Vodovotz, Y.
Minervini, M.
Scott, V.
Soltys, K.
Shiva, S.
Paranjpe, S.
Sadowsky, D.
Barclay, D.
Zamora, R.
Stolz, D.
Demetris, A.
Michalopoulos, G.
Marsh, J. W.
author_facet Fontes, P.
Lopez, R.
van der Plaats, A.
Vodovotz, Y.
Minervini, M.
Scott, V.
Soltys, K.
Shiva, S.
Paranjpe, S.
Sadowsky, D.
Barclay, D.
Zamora, R.
Stolz, D.
Demetris, A.
Michalopoulos, G.
Marsh, J. W.
author_sort Fontes, P.
collection PubMed
description We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions (21°C) with a new hemoglobin‐based oxygen carrier (HBOC) solution. MP (n = 6) was compared to cold static preservation (CSP; n = 6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5‐day follow‐up. Recipients' peripheral blood, serial liver biopsies, preservation solutions and bile specimens were collected before, during and after liver preservation. Clinical laboratorial and histological analyses were performed in addition to mitochondrial functional assays, transcriptomic, metabolomic and inflammatory mediator analyses. Compared with CSP, MP animals had: (1) significantly higher survival (100% vs. 33%; p < 0.05); (2) superior graft function (p < 0.05); (3) eight times higher hepatic O(2) delivery than O(2) consumption (0.78 mL O(2)/g/h vs. 0.096 mL O(2)/g/h) during MP; and (4) significantly greater bile production (MP = 378.5 ± 179.7; CS = 151.6 ± 116.85). MP down‐regulated interferon (IFN)‐α and IFN‐γ in liver tissue. MP allografts cleared lactate, produced urea, sustained gluconeogenesis and produced hydrophilic bile after reperfusion. Enhanced oxygenation under subnormothermic conditions triggers regenerative and cell protective responses resulting in improved allograft function. MP at 21°C with the HBOC solution significantly improves liver preservation compared to CSP.
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spelling pubmed-50240422016-09-23 Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions Fontes, P. Lopez, R. van der Plaats, A. Vodovotz, Y. Minervini, M. Scott, V. Soltys, K. Shiva, S. Paranjpe, S. Sadowsky, D. Barclay, D. Zamora, R. Stolz, D. Demetris, A. Michalopoulos, G. Marsh, J. W. Am J Transplant Original Articles We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions (21°C) with a new hemoglobin‐based oxygen carrier (HBOC) solution. MP (n = 6) was compared to cold static preservation (CSP; n = 6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5‐day follow‐up. Recipients' peripheral blood, serial liver biopsies, preservation solutions and bile specimens were collected before, during and after liver preservation. Clinical laboratorial and histological analyses were performed in addition to mitochondrial functional assays, transcriptomic, metabolomic and inflammatory mediator analyses. Compared with CSP, MP animals had: (1) significantly higher survival (100% vs. 33%; p < 0.05); (2) superior graft function (p < 0.05); (3) eight times higher hepatic O(2) delivery than O(2) consumption (0.78 mL O(2)/g/h vs. 0.096 mL O(2)/g/h) during MP; and (4) significantly greater bile production (MP = 378.5 ± 179.7; CS = 151.6 ± 116.85). MP down‐regulated interferon (IFN)‐α and IFN‐γ in liver tissue. MP allografts cleared lactate, produced urea, sustained gluconeogenesis and produced hydrophilic bile after reperfusion. Enhanced oxygenation under subnormothermic conditions triggers regenerative and cell protective responses resulting in improved allograft function. MP at 21°C with the HBOC solution significantly improves liver preservation compared to CSP. John Wiley and Sons Inc. 2015-02 2015-01-22 /pmc/articles/PMC5024042/ /pubmed/25612645 http://dx.doi.org/10.1111/ajt.12991 Text en © 2015 The Authors. American Journal of Transplantation Published by The American Society of Transplantation and the American Society of Transplant Surgeons This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/3.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/3.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Fontes, P.
Lopez, R.
van der Plaats, A.
Vodovotz, Y.
Minervini, M.
Scott, V.
Soltys, K.
Shiva, S.
Paranjpe, S.
Sadowsky, D.
Barclay, D.
Zamora, R.
Stolz, D.
Demetris, A.
Michalopoulos, G.
Marsh, J. W.
Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title_full Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title_fullStr Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title_full_unstemmed Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title_short Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions
title_sort liver preservation with machine perfusion and a newly developed cell‐free oxygen carrier solution under subnormothermic conditions
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024042/
https://www.ncbi.nlm.nih.gov/pubmed/25612645
http://dx.doi.org/10.1111/ajt.12991
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