Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death

PLoS One. 2014 Feb 14;9(2):e88521. doi: 10.1371/journal.pone.0088521. eCollection 2014.

Abstract

Background: Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model.

Methods: After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system.

Results: After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024).

Conclusions: Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / drug effects
  • Arterioles / pathology*
  • Aspartate Aminotransferases / blood
  • Biliary Tract / blood supply
  • Biliary Tract / drug effects
  • Biliary Tract / innervation*
  • Death
  • Epithelium / drug effects
  • Epithelium / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Hypothermia, Induced*
  • L-Lactate Dehydrogenase / blood
  • Liver / blood supply*
  • Liver / drug effects
  • Liver / pathology
  • Liver Transplantation
  • Necrosis
  • Nerve Fibers / drug effects
  • Nerve Fibers / pathology*
  • Organ Preservation
  • Oxidative Stress / drug effects
  • Oxygen / pharmacology*
  • Perfusion*
  • Reperfusion
  • Sus scrofa
  • Tissue and Organ Procurement

Substances

  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Oxygen

Grants and funding

This research work was financially supported by grants provided by Innovatief Actieprogramma Groningen (IAG-3) and the Jan Kornelis de Cock Stichting in The Netherlands. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.