Iloprost donor treatment reduces ischemia-reperfusion injury in an isolated extracorporeal pig liver perfusion model

Exp Clin Transplant. 2015 Feb;13(1):51-61.

Abstract

Objectives: Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model.

Materials and methods: German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2 L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4).

Results: Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens. Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls.

Conclusions: Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bile / metabolism
  • Blood Flow Velocity
  • Cold Ischemia / adverse effects*
  • Cytoprotection
  • Disease Models, Animal
  • Extracorporeal Membrane Oxygenation*
  • Iloprost / pharmacology*
  • Liver / blood supply*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Circulation / drug effects
  • Liver Transplantation / adverse effects*
  • Microcirculation / drug effects
  • Organ Preservation / methods*
  • Organ Preservation Solutions / pharmacology*
  • Oxygen Consumption / drug effects
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Swine
  • Time Factors
  • Tissue and Organ Harvesting

Substances

  • Organ Preservation Solutions
  • Iloprost