Background: Prostaglandin E1 (PgE1) may have a role in ameliorating hepatic ischaemia–reperfusion injury (IRI). Metabolism occurs after intravenous administration of PgE1 and limits its efficacy. This study has investigated the cytoprotective effect of PgE1 administered intraportally. Since leucocyte–endothelial cell adhesion has been strongly implicated in IRI, we also studied intracellular adhesion molcule‐1 (ICAM‐1) and vascular adhesion molecule‐1 (VCAM‐1) expression to assess if PgE1 acted through this pathway.
Methods: Under general anaesthesia hepatic ischaemia was induced in 20 canine livers by 60 min of in situ inflow occlusion with continuous intraportal infusion of PgE1 0.02 µg kg−1 per min lactated Ringers solution (n = 10) or equal volumes of lactated Ringers solution (controls, n = 10). The infusion started 15 min before ischaemia and continued during the ischaemic phase and 30 min after reperfusion. Hepatic venous blood and liver biopsies were taken at baseline, 60‐min ischaemia and 30‐min reperfusion. The blood samples were assessed for liver enzymes, TNF‐α, IL‐1β, serum ICAM‐1 (sICAM‐1) and VCAM‐1 (sVCAM‐1), while the liver biopsies were assessed histologically for IRI and immunohistochemically for ICAM‐1 and VCAM‐1 expression.
Results: PgE1 treatment significantly reduced the rise in AST, ALT, TNF‐α, sICAM‐1 and sVCAM‐1 following ischaemia and reperfusion (P < 0.05). It reduced hepatocyte necrosis and sinusoidal congestion. However, it did not reduce IL‐1β. These changes were associated with significant down‐regulation of ICAM‐1 and VCAM‐1 (P < 0.05).
Conclusion: Intraportal PgE1 infusion ameliorates IRI, inhibits ICAM‐1 and VCAM‐1 expression and TNF‐α secretion. One of the mechanisms of cytoprotection may be through ICAM‐1 and VCAM‐1 inhibition.
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