Metabolic preconditioning with fructose prior to organ recovery attenuates ischemia-reperfusion injury in the isolated perfused rat liver

Abstract

Objective. Ischemia-reperfusion injury is associated with a high rate of primary organ dysfunction and thereby contributes substantially to morbidity and mortality in the course of liver transplantation. In the present study, the impact of metabolic preconditioning with fructose on ischemia-reperfusion injury in the isolated perfused rat liver model is evaluated. Methods. Fasted rats received a single intravenous fructose injection to induce metabolic preconditioning (fructose group) or a volume equivalent of normal saline (control group) 10 min before liver explantation. After 26 h of cold storage, livers were reperfused for 90 min at 37°C with Krebs-Henseleit buffer. The parameters used to quantify ischemia-reperfusion injury included hepatic oxygen consumption, enzyme release, and cell viability. Results. During reperfusion, livers in the fructose group consumed more oxygen than livers in the control group (p < 0.005), indicating ATP synthesis as a result of glycolytic fructose degradation. Moreover, cell injury was reduced by fructose administration, as reflected by a lower enzyme release during both cold ischemia and reperfusion (p < 0.05). Finally, hepatocyte viability at the end of reperfusion was significantly higher in the fructose group (p < 0.01). However, there was no significant difference between the two experimental groups in reference to the viability of endothelial cells. Conclusion. In clinical use, metabolic preconditioning with fructose prior to organ recovery might contribute to a reduction in the incidence of primary organ dysfunction after liver transplantation.

Key Words::

• cold ischemia
• fructose
• ischemia-reperfusion injury
• liver
• preconditioning
• reactive oxygen species
• reperfusion

Acknowledgments

The authors express their gratitude to Richard Wojtaschewski (1948–2007) for his outstanding precision mechanical support during the development phase of the perfusion model.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.