Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation

PLoS One. 2020 Jul 2;15(7):e0235635. doi: 10.1371/journal.pone.0235635. eCollection 2020.

Abstract

Background: Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).

Methods: Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.

Results: Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.

Conclusion: Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects
  • Bile / metabolism
  • Bile Ducts / pathology
  • Dipyrone / pharmacology*
  • Hepatic Artery / pathology
  • Liver / blood supply
  • Liver / pathology
  • Liver Function Tests
  • Liver Transplantation*
  • Male
  • Organ Preservation / methods*
  • Rats
  • Rats, Wistar
  • Vasodilation / drug effects*

Substances

  • Dipyrone

Grant support

This work was funded by institutional financial support of the Charité – Universitätsmedizin Berlin, the German Research Foundation (grant number: RA 3044/3-1) and by a Kickbox Seed Grant of the Einstein Center for Regenerative Therapies. Nathanael Raschzok is fellow of the BIH Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health.