Ischaemic Preconditioning and Intermittent Clamping does not Influence Mediators of Liver Regeneration in a Human Hepatocyte Model of Ischaemia-Reperfusion Injury

Abstract

AIM: The role of ischaemic preconditioning (IPC) on liver regeneration following surgery remains inconclusive. The aim of the study was to assess the effect of IPC on mediators involved in regeneration produced by human hepatocytes, using an in-vitro hypoxia-reoxygenation model to mimic ischaemia-reperfusion injury (IRI).

METHODS: Following extraction from samples obtained from liver resection (n=5), confluent culture flasks of hepatocytes were subjected to IRI (1 hour hypoxia + 1 hour reoxygenation), IPC prior to IRI (10 minutes hypoxia + 10 minutes reoxygenation + 1 hour hypoxia + 1 hour reoxygenation), intermittent clamping (IC, 15 minutes hypoxia + 5 minutes reoxygenation x3 + 1 hour reoxygenation) and compared to controls. The production of various mediators was determined over 48 hours.

RESULTS: Interleukin (IL)-8, granulocyte-colony stimulating factor (G-CSF) and IL-1-receptor antagonist (IL-1ra) were produced by hepatocytes. IPC prior to IRI did not influence the production of IL-8, G-CSF and IL-1ra by hepatocytes compared to IRI over the study period. Similarly, IC did not significantly influence the profile of these mediators compared to IRI in this model.

CONCLUSION: IPC, as well as IC did not influence the production of pro-regenerative mediators in a hepatocyte model of IRI. The role of IPC in liver regeneration remains to be determined.