Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions

P. Fontes*, R. Lopez, A. Van Der Plaats, Y. Vodovotz, M. Minervini, V. Scott, K. Soltys, S. Shiva, S. Paranjpe, D. Sadowsky, D. Barclay, R. Zamora, D. Stolz, A. Demetris, G. Michalopoulos, J. W. Marsh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

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 O2 delivery than O2 consumption (0.78 mL O2/g/h vs. 0.096 mL O2/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.

Original languageEnglish
Pages (from-to)381-394
Number of pages14
JournalAmerican Journal of Transplantation
Volume15
Issue number2
DOIs
StatePublished - 1 Feb 2015
Externally publishedYes

Keywords

  • animal models: porcine
  • basic (laboratory) research/science
  • donors and donation: donation after circulatory death (DCD)
  • ischemia reperfusion injury (IRI)
  • liver transplantation/hepatology
  • metabolomics
  • organ perfusion and preservation
  • pathology/histopathology
  • regenerative medicine

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