Lung inflammation after brain death: sex differences and treatment strategies

It is important to investigate the impact of brain death (BD) on lung quality since the majority of donors are brain dead. BD induces a hemodynamic, immune and hormonal imbalance, where the lungs are especially affected. Clinical evidence often neglects the impact of sex differences in transplantation. There is a possible correlation between transplant prognostic and donor-receptor sex match, where the worse combination was female donors and male receptors. Physiological and molecular aspects initiated by BD could differ between sexes. Studies associate the loss of the pituitary-hypothalamus-ovaries axis with the greater lung inflammation in female rats. In our study, we show the importance of the female sex hormones (FSH) after BD in the development of lung inflammation, especially estradiol. Based on the relation between inflammatory response and coagulation, in another study we have shown sex differences in the coagulation process after BD; where females present microcirculation preservation and males microthrombi formation, reducing the perfusion. In parallel, lung evaluation after BD followed by ex vivo perfusion confirmed the greater inflammation in female lungs, compared to males. Considering the importance of FSH on inflammation, we investigated estradiol effects in females after BD, showing reduction of lung inflammation, with protective effects after maintaining the animals for 6 h and 24h after. Finally, our data indicate that estradiol could have acute and long-lasting effects, thus increasing lung graft quality. Therefore, we could conclude that an estradiol treatment could be considered as a therapeutic agent in brain dead donors and/or during lung ex vivo perfusion.