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INFLUENCE OF BRAIN DEAD DONORS WITH ESTRADIOL TREATMENT ON LUNG PRIMARY GRAFT DYSFUNCTION

Grant number: 21/13020-6
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2023
Effective date (End): June 30, 2025
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Luiz Felipe Pinho Moreira
Grantee:Fernanda Yamamoto Ricardo da Silva
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

Abstract

The available treatment in advanced lung diseases is lung transplantation, with most grafts coming from individuals in brain death (BD). The etiology and BD per se affect organ viability for transplant recipients, with the lung being one of the organs most affected by BD repercussions. These generate hemodynamic instability, immunological and inflammatory changes, which are the result of pituitary failure. The effects of BD together with ischemia and reperfusion, inherent to transplant, are determining factors to the success of transplant and development of primary graft disfunction in patients. Clinical studies highlight that the combination of female donors with male recipients presents a higher risk of transplant outcome. Where female sex is possibly associated with the development of primary graft dysfunction. Experimental studies indicate that the differences between donors in BD occur due to the resulting pulmonary inflammation, with females showing a more exacerbated inflammatory response than males, which may generate greater post-transplant repercussions. Female sex hormones, especially estradiol, are considered pulmonary protection factors in cases of trauma/sepsis. Thus, in the case of BD, they are pointed out as one of the factors responsible for sexual dimorphism. Since, in BD models, after the loss of the hypothalamic-pituitary-ovarian axis, such protection is lost in females. Previous studies by the group indicate that treatment with estradiol attenuates pulmonary inflammation after the establishment of BD, possibly exerting long-term effects. Thus, in the present study, we intend to evaluate the repercussions of a treatment with estradiol in the lungs of donors of both sexes undergoing BD after lung transplantation. Thus, it will be possible to understand if the reduction of lung inflammation in treated donors with estradiol reflects positively in the primary graft disfunction, mechanisms involved and lung transplant.

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