Evaluation of the effects of 17-beta estradiol on pulmonary injury induced by brain death in female rats

Abstract

Organ transplantation from brain dead individuals is the possible treatment for many patients in endstage of disease. The lung is one of the most affected organs by the brain death, which is associated to hemodynamic instability and inflammatory and immunological alterations, affecting the organs quality for transplantation. Studies highlight the worse outcome of lung transplant with female organs. It is important to mention that in a previous study of our group the evaluation of the pulmonary inflammation caused by brain death, showed more severe inflammatory status in female rats, accompanied by acute reduction of female sex hormones concentrations. Important hormonal and metabolic changes occur after hypothalamic/pituitary failure in experimental models of brain death and those changes associated to brain death previous events (such as trauma and bleeding) add to inflammatory result of organ donors.Clinical and experimental studies reveal the estradiol protective effect on immune system, pulmonary inflammation and inflammatory mediators release. The estradiol role as vascular and immune modulator could influence the events triggered by brain death. These results reinforce the significance of the investigation of estradiol treatment effects on systemic and pulmonary inflammatory response in female rats, besides evaluating its therapeutic effects after brain death. Thus this project aim is to investigate the estradiol treatment effect on lung inflammation after brain death. We intend to evaluate: (1) leukocyte mobilization from bone marrow to blood and lung; (2) lung microvascular permeability and myeloperoxidase activity; (3) systemic and local release of inflammatory mediators; (4) lung protein expression of adhesion molecules, nitric oxide synthases, endothelin and MMP-9; (5) nitric oxide synthases, endothelin and MMP-9 gene expression on lung tissue; (6) in vitro leukocyte chemotaxis; (7) lung microcirculation by intravital microscopy; (8) gas exchange. (AU)