Study of the therapeutic effects of estradiol and prednisolone on lung of brain dead female rats after ex vivo perfusion

• Grant number: 21/07455-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): February 10, 2022
• Effective date (End): February 09, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Cristina Breithaupt Faloppa
• Grantee: Marina Vidal dos Santos
• Supervisor: Hendrik Gerrit Derk Leuvenink
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Research place: University Medical Center Groningen (UMCG), Netherlands
• Associated to the scholarship: 20/11211-6 - Study of the therapeutic effects of 17beta-estradiol and prednisolone association in pulmonary inflammation on female rats subject to brain death, BP.DD

Abstract

Organ transplantation is the possible treatment for many patients in endstage of disease, and the majority of organs are obtained from brain dead patients. Brain death (BD) leads to a systemic inflammatory process associated with hormonal, metabolic and hemodynamic changes and the lung is one of the organs most affected. Previous studies of pulmonary inflammation caused by BD, showed a more relevant inflammatory frame in female rats and the worst outcome of lung transplantation with organs from female donos, which was associated with an acute reduction of female sex hormones, especially estradiol. The pituitary failure resulting from BD causes the reduction of several hormones, like glicocorticoids, T3, T4 and sexual hormones, which compromises the donor's response to the inflammatory process. In females, estradiol is related to cortisol release and action. Female sex hormones regulate corticosteroids levels by blocking the negative feedback of its receptors. Also, studies suggest that both hormones act in a co-dependent manner. In previous studies from our group, estradiol treatment after BD in female rats reduced lung inflammation and improved cardiac function. Besides, several studies indicate that donor hormonal replacement with corticosteroids after BD contributes to improving the quality of several organs for transplantation, including the lung, by improving hemodynamic and reducing inflammation. Another alternative to increase lung donation is the recovery of marginal lungs using ex vivo lung perfusion (EVLP). EVLP was first used to assess organ quality, but now it allows marginal organs to be treated and become available for transplantation. Few studies have described the use of hormonal therapy in the EVLP. Owing to the anti inflammatory actions of estradiol and corticoids, and considering that both hormones have already shown positive results in ameliorating lungs after BD, we aim to investigate the effect of estradiol and prednisolone treatment during EVLP, focusing in improving the quality of marginal lungs. (AU)