Evaluation of 17β-estradiol treatment in rat lungs after circulatory death using in situ perfusion

Lung transplantation from circulatory dead donors represents a therapeutic option for end-stage pulmonary diseases. The lungs are particularly vulnerable organs and are associated with extended transplantation waiting lists. The hormone 17β-estradiol (E2) has been shown to reduce pulmonary damage caused by acute lung injury, exert a protective effect against pulmonary oedema, and attenuate cytokine release. The present study aimed to investigate the effects of E2 on the inflammatory profile of DCD donor lungs using a standardized method of in situ perfusion.

Male Wistar rats underwent circulatory death induced by intravenous administration of 19.1% KCl solution, followed by 30 min of warm ischaemia without ventilation. Then, lungs were subjected to one of three conditions: cold storage at 4 °C for 2 h (Control); in situ perfusion for 2 h with Perfadex in an open circuit at 37 °C via the pulmonary artery (P); or perfusion under the same conditions with the addition of E2 to the perfusate (E2). Lungs were then collected for histopathological evaluation. Tissue biopsies were obtained for gene expression analysis (PCR) and for ELISA protein quantification. In addition, lung fragments were collected for explant analysis, maintained in culture for 24 h.

E2 lungs showed less haemorrhage than the Control group (p = 0.0485). Control lung homogenates presented lower gene expression of eNOS (p = 0.0008) and ICAM-1 (p = 0.0537) than P. After perfusion, the E2 group expressed less eNOS (p = 0.0011) than the P group. In the perfusate, IL-10 in the E2 group was lower than P (p = 0.0140).

In this standardized DCD model, warm ischemia caused limited lung inflammation. Because E2 mainly targets pulmonary inflammation, these findings suggest that E2 use may offer limited benefit in this specific setting.