Menopause worsens donor lungs status after brain death

Background: Lung transplantation is an established treatment for end-stage pulmonary diseases; however, organ scarcity remains a major limitation. The lung is particularly vulnerable to injury following brain death (BD), and evidence indicates that females may exhibit a heightened inflammatory response, possibly related to abrupt reductions in female sex hormones. In parallel, demographic shifts have increased the proportion of older donors, emphasizing the need to better understand menopause-associated changes in female lung donors.
Methods: Our study investigated the effects of menopause on pulmonary inflammation in female rats subjected to BD, focusing on inflammatory mediators and leukocyte trafficking. To  this  end,  adult  female  Wistar  rats  underwent  menopause  induction  using 4-vinylcyclohexene diepoxide, followed by a period of aging, with menopause confirmed by hormonal analysis. Subsequently, BD was induced by intracranial balloon inflation, and animals were mechanically ventilated for six hours, while sham-operated rats served as controls. Blood counts, bone marrow cellularity, bronchoalveolar lavage, serum inflammatory mediators were quantified. Lung histopathology and cytokine release from lung tissue cultures and immunohistochemistry for inflammatory markers were analyzed.
Results: Menopausal rats exhibited disrupted estral cycles, reduced estradiol levels, and elevated follicle-stimulating hormone. Following BD, leukopenia was observed in both young and menopausal animals; however, menopausal BD rats showed reduced circulating granulocytes alongside increased granulocyte infiltration into the lungs and higher bone marrow cellularity. Moreover, anti-inflammatory IL-10 levels were reduced in menopausal BD animals, whereas pro-inflammatory cytokines IL-1β and IL-6 were increased in lung tissue cultures. Menopause also increased lung edema and hemorrhage. Immunohistochemical analysis indicated higher ICAM-1 and iNOS expression after menopause.
Conclusion: Menopause alters the pulmonary inflammatory response by generating a proinflammatory status that, following BD, is worsened especially by enhancement of leukocyte recruitment to lung tissue. These insights may contribute to improved donor evaluation and management strategies in lung transplantation.