Preconditioning of donor livers with prostaglandin I2 before retrieval decreases hepatocellular ischemia-reperfusion injury

Abstract

Background: Prostaglandins have been shown to protect against a variety of liver insults, including ischemia-reperfusion injury. Decreased graft injury and improved survival have been demonstrated in animal studies of liver transplantation after donor pretreatment with prostaglandin before organ retrieval. This potential clinical application has not been examined in human subjects.

Patients and methods: One hundred and six liver donors were randomly assigned to receive either prostaglandin I2 (epoprostenol, 500 microg intravenous bolus) immediately before cold perfusion or no drug as control. Donor and recipient characteristics were recorded, and liver function tests were monitored after transplant to assess the effect of epoprostenol on graft injury.

Results: Donor pretreatment with epoprostenol significantly improved the rapidity and homogeneity of graft reperfusion. Epoprostenol pretreatment also significantly reduced peak values of transaminases after transplantation: serum glutamic-pyruvic transaminase, control (851+/-121 international units [IU]/L) and epoprostenol (463+/-78 IU/L); serum glutamic-oxalaacetic transaminase, control (870+/-127 IU/L) and epoprostenol (463+/-78 IU/L); serum glutamate dehydrogenase, control (458+/-95 IU/L) and epoprostenol (170+/-30 IU/L); P<0.01 for all, by t test. Serum levels of bilirubin and alkaline phospatase were not significantly altered by donor pretreatment with epoprostenol.

Conclusions: Reduction of ischemia-reperfusion injury by administration of epoprostenol before graft retrieval may have important applications in liver transplantation. Further studies are required to establish the mechanism of this effect and to define its precise role in clinical practice.