Ezetimibe pretreatment attenuates early ischemia-reperfusion injury in a rat model of lung transplantation.

Ischemia-reperfusion injury (IRI) after transplantation causes early and late graft dysfunction. Ezetimibe (Eze) is a lipid-reducing agent that has been reported to attenuate oxidative stress and inflammation in non-pulmonary models of ischemia-reperfusion. We examined its effect in a rat lung transplantation model. Lewis rats (n = 8/group) underwent left lung transplantation without pretreatment (LT) or with Eze pretreatment of the donor (LT-D), recipient (LT-R), or both (LT-DR). Eze (1 mg/kg) was given orally three times weekly for 2 weeks, and donor lungs were transplanted after 6 h of cold storage. Graft gas exchange, histology, inflammation, and apoptosis were assessed after 2 h of reperfusion. Graft PaO2/FiO2, measured with the contralateral hilum clamped, differed among the groups (176.8 ± 149.6, 265.1 ± 124.3, 321.9 ± 130.2, and 412.6 ± 142.3 mmHg in LT, LT-D, LT-R, and LT-DR; p = 0.015) and was significantly higher than in LT only in LT-DR. All treatment groups had lower lung injury scores than LT (16.62 ± 0.65 vs 12.25 ± 0.78, 10.95 ± 0.46, and 10.72 ± 0.40; p < 0.001). Plasma inflammatory cytokines and lung tissue myeloperoxidase were also lower in the treatment groups, and TUNEL positivity was significantly lower only in LT-DR. In conclusion, Eze pretreatment attenuated early IRI in a rat model of lung transplantation. Because the AMPK/Nrf2 pathway and direct indices of oxidative stress were not measured, the mechanism of this protection remains undetermined, and the findings are confined to the first 2 h after reperfusion.