Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results

J Surg Res. 2011 May 15;167(2):e365-73. doi: 10.1016/j.jss.2010.01.038. Epub 2010 Feb 21.

Abstract

Background: Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function.

Methods: We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. Liver allografts underwent HMP for 4-7 h using dual centrifugal perfusion with Vasosol solution at 4-8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism.

Results: We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP.

Conclusions: HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.

Publication types

  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Biopsy
  • Humans
  • Hypothermia, Induced / instrumentation*
  • Hypothermia, Induced / methods*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-8 / metabolism
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology*
  • Liver Transplantation / physiology*
  • Middle Aged
  • Organ Preservation / methods*
  • Organ Preservation Solutions / pharmacology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Interleukin-8
  • Organ Preservation Solutions
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1