Science and Research

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6 h directly after procurement (control group) or after 20 h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2 h after reperfusion (11,012 ng/ml vs. 1,493 ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2 h of reperfusion (706.00 ng/ml vs. 148.20 ng/ml; p < 0.001) and showed positive correlations with AST (r (2) = 0.846) and GLDH (r (2) = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury.
  • Beetz, O.
  • Cammann, S.
  • Weigle, C. A.
  • Sieg, L.
  • Eismann, H.
  • Johanning, K.
  • Falk, C. S.
  • Krech, T.
  • Oldhafer, F.
  • Vondran, F. W. R.

Keywords

  • Animals
  • Swine
  • *Liver Transplantation/adverse effects
  • Organ Preservation
  • Interleukin-18
  • Swine, Miniature
  • Perfusion
  • Liver
  • Hmgb1
  • Il-18
  • cytokine
  • extended criteria donor organs
  • ischemia-reperfusion injury
  • marginal organs
  • normothermic machine perfusion
Publication details
DOI: 10.3389/ti.2022.10712
Journal: Transpl Int
Pages: 10712 
Work Type: Original
Location: BREATH
Disease Area: General Lung and Other
Partner / Member: MHH
Access-Number: 36338535

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