Introduction: Lung transplantation is a treatment option for patients in advanced stages of disease, however the reduced number of available organs is an obstacle to its effectiveness. The lung is one of the most affected organs by brain death (BD), with female presenting greater inflammatory response than male, related to an acute reduction of female sex hormones. With the aging of the world population, older donors have been increasing in numbers. For female donors the important alterations during menopause period should be considered and evaluated. Thus, the objective of this study was to investigate the effects of menopause in rats subjected to brain death, analyzing the release of inflammatory mediators and leukocyte influx to the lungs.
Methods: Groups of adult female Wistar rats were submitted to menopause induction by the injection of 4-vinylcyclohexene diepoxide (VCD, i.p. 80 mg/kg, 5 d/w) for 6 weeks. After the ovarian follicular depletion, the rats were kept for 10 weeks in order to age. To confirm the menopause, blood samples were used to quantify 17β-estradiol and FSH. For the BD model, young female and menopausal rats had a balloon catheter rapidly inflated in the intracranial space and were maintained for 6 h with mechanical ventilation. Respective sham-operated (S) were used as controls. WBC, bone marrow and bronchoalveolar lavage (BAL) counts were analyzed, and serum inflammatory mediators quantified. Lung tissue fragments were collected for histopathological analysis and kept in culture (explant) for analysis of inflammatory mediators release (24 h).
Results: Menopausal female rats (M) presented irregular estral cycles with significantly lower estradiol (p<0.001) and higher FSH levels than in young females (Y) (p = 0.0140). After 6 h of BD, WBC counts showed reduced cell numbers in menopause (p=0.014) and young rats (p=0.011) compared to respective Sham. M-BD presented lower numbers of granulocytes in the blood than Y-BD (p=0.01). In BAL, M-BD rats had a greater number of cells, mainly granulocytes, in comparison to respective Sham (p=0.018) and to Y-BD (p=0.009). Bone marrow total cells were increased in M-BD in comparison to Y-BD (p=0.035). In relation to serum mediators, IL-10 was reduced in M-BD in comparison to Y-BD (p=0.003). BD was able to increase IL-1β and IL-6 concentrations in lung culture media of menopause and young females.
Conclusion: Data evidenced the influence of menopause in the lung inflammatory response induced by brain death, mainly by increasing the leukocyte infiltration to the lungs. Our results allow us to conclude that menopause affects the lung response to BD and understanding its pathways may contribute to this type of donor ideal maintenance.