EVALUATION OF THE EFFECTS OF 17beta-ESTRADIOL ON MICROCIRCULATORY CHANGES INDUCED BY BRAIN DEATH IN MALE RATS

• Grant number: 16/13632-3
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2016
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Paulina Sannomiya
• Grantee: Paulina Sannomiya
• 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
• Associated researchers: Ana Cristina Breithaupt Faloppa ; Luiz Felipe Pinho Moreira

Abstract

A functional microvascular system is essential for adequate tissue oxygenation, particularly in solid organs used for transplantation. Recent studies have shown that microvascular damage seems to be an important cause of early and long-term lung graft failure. Experimental evidence indicates that brain death triggers a persistent mesenteric hypoperfusion, endothelial activation and leukocyte migration associated with reduced levels of endogenous corticosterone. Hormonal changes secondary to pituitary failure cause hemodynamic and metabolic changes, which potentiate the degenerative process in the organs after brain death. Clinical and experimental evidence indicates that sex hormones influence the course of the inflammatory response, highlighting the beneficial effect of the female hormone estrogen and the deleterious effect of the male hormone testosterone. Furthermore, gonadal steroid 17beta-estradiol protects against cardiovascular ischemic, metabolic and inflammatory lesions. However, there are no data about the role of this hormone on microcirculatory changes due to brain death. This study aims to investigate the action of 17beta-estradiol on mesenteric and lung microcirculation after brain death in male rats. It is intended to investigate: (1) mesenteric microcirculatory changes such as perfusion, leukocyte-endothelial interactions and expression of adhesion molecules; (2) lung edema, leukocyte infiltration, and expression of adhesion molecules on microvessels; (3) protein and gene expression of nitric oxide synthases and endothelin in the mesentery and lung; (4) levels of serum cytokines; (5) white blood cell counts, haemodynamic and blood gas variables; (6) levels of serum estradiol and corticosterone. (AU)

Scientific publications

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VIEIRA, ROBERTA FIGUEIREDO; BREITHAUPT-FALOPPA, ANA CRISTINA; MATSUBARA, BRUNO CARVALHO; RODRIGUES, GEOVANA; SANCHES, MARCELO PETROF; FERREIRA, SUELI GOMES; CORREIA, CRISTIANO DE JESUS; MOREIRA, LUIZ FELIPE; SANNOMIYA, PAULINA. EFFECTS OF 17BETA-ESTRADIOL ON A SUDDEN ONSET BRAIN DEATH MODEL IN MALE RATS. Transplant International, v. 30, p. 2-pg., 2017-09-01. (16/13632-3)

VIEIRA, ROBERTA; BREITHAUPT-FALOPPA, ANA CRISTINA; MATSUBARA, BRUNO CARVALHO; FERREIRA, SUELI GOMES; DEJESUSCORREIA, CRISTIANO; MOREIRA, LUIZ FELIPE; SANNOMIYA, PAULINA. 17 beta-ESTRADIOL AS A NEW THERAPY TO PRESERVE MICROCIRCULATORY PERFUSION IN SMALL BOWEL DONOR. Transplant International, v. 32, p. 2-pg., 2019-10-01. (16/13632-3)

VIEIRA, ROBERTA FIGUEIREDO; BREITHAUPT-FALOPPA, ANA CRISTINA; CORREIA, CRISTIANO JESUS; ARMSTRONG, JR., ROBERTO; COUTINHO-E-SILVA, RAPHAEL DOS SANTOS; FERREIRA, SUELI GOMES; MOREIRA, LUIZ FELIPE PINHO; SANNOMIYA, PAULINA. 17 beta-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors. TRANSPLANTATION, v. 104, n. 9, p. 1862-1868, SEP 2020. (16/13632-3)

VIEIRA, ROBERTA FIGUEIREDO; BREITHAUPT-FALOPPA, ANA CRISTINA; MATSUBARA, BRUNO CARVALHO; RODRIGUES, GEOVANA; SANCHES, MARCELO PETROF; ARMSTRONG-, JR., ROBERTO; FERREIRA, SUELI GOMES; CORREIA, CRISTIANO DE JESUS; MOREIRA, LUIZ FELIPE P.; SANNOMIYA, PAULINA. 17 beta-Estradiol protects against lung injuries after brain death in male rats. JOURNAL OF HEART AND LUNG TRANSPLANTATION, v. 37, n. 11, p. 1381-1387, NOV 2018. (16/13632-3)