The effect of amifostine on lung ischaemia-reperfusion injury in rats.

Abstract

Lung ischaemia-reperfusion injury (LIRI) frequently occurs after lung transplantation or cardiac surgery with cardiopulmonary bypass, thus increasing postoperative morbidity and mortality. As LIRI is associated with the release of reactive oxygen species and a subsequent inflammatory reaction, we tested whether amifostine, a thiol and free radical scavenger, has a beneficial effect on LIRI. A total number of 72 Wistar rats were subjected to LIRI with or without a single or double dose of amifostine (100 mg/kg, intraperitoneally). Experimental induction of LIRI was performed by clamping either the left lung hilum or the pulmonary artery alone for 60 min, followed by 90 min of reperfusion. Control groups consisted of LIRI and NaCl, a sham group and a no intervention group (baseline). At the end of the experiments, the left lung was analysed by quantitative RT-PCR of inflammatory marker gene expression, western blot of activated nuclear factor-κB (NF-κB) and light and electron microscopy. In placebo and amifostine groups, the expression levels of pro-inflammatory markers were increased significantly and to a similar extent independent of the type of ischaemia induction. In contrast, amifostine reduced the activation of NF-κB in comparison with placebo. This effect was present independent of the type of ischaemia or the application of a single or double dose of amifostine. However, oedema formation, blood-gas barrier damage and inflammatory reaction were similar in all amifostine or placebo LIRI groups. Despite a significant reduction in NF-κB activation, amifostine failed to decrease the inflammatory response and structural changes induced by LIRI in this experimental setting.