Treatment with 17 beta-estradiol protects donor heart against brain death effects in female rat

Roberto Armstrong-Jr, Fernanda Yamamoto Ricardo-da-Silva, Cristiano Jesus Correia, Marina Vidal-dos-Santos, Lucas Ferreira da Anunciacao, Raphael Santos Coutinho e Silva, Luiz Felipe Pinho Moreira, Hendrik Gerrit Derk Leuvenink, Ana Cristina Breithaupt-Faloppa*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The viability of donor organs is reduced by hemodynamic and immunologic alterations caused by brain death (BD). Female rats show higher heart inflammation associated with the reduction in female sex hormones after BD. This study investigated the effect of 17 beta-estradiol (E2) on BD-induced cardiac damage in female rats. Groups of female Wistar rats were assigned: Sham-operation (Sham), brain death (BD), treatment with E2 (50 mu g/ml, 2 ml/h) 3 h after BD (E2-T3), or immediately after BD confirmation (E2-T0). White blood cell (WBC) count was analyzed; cytokines and troponin-I were quantified. Heart histopathological changes and expression of endothelial nitric oxide synthase, endothelin-1, intercellular adhesion molecule-1, BCL-2, and caspase-3 were evaluated. Cardiac function was continuously assessed for 6 h by left ventricular pressure-volume loop analysis. E2 decreased the BD-induced median serum concentration of troponin-I (BD:864.2 vs. E2-T0:401.4;P = 0.009), increased BCL-2 (BD:0.086 vs. E2-T0:0.158; P = 0.0278) and eNOS median expression in the cardiac tissue (BD:0.001 vs. E2-T0:0.03 and E2-T3:0.0175; P <0.0001), and decreased caspase-3 (BD:0.025 vs. E2-T0:0.006 and E2-T3:0.019; P = 0.006), WBC counts, leukocyte infiltration, and hemorrhage. 17 beta-estradiol treatment was effective in reducing cardiac tissue damage in brain-dead female rats owing to its ability to reduce leukocyte infiltration and prevent cardiomyocyte apoptosis.

Original languageEnglish
Pages (from-to)1312-1321
Number of pages10
JournalTransplant International
Volume33
Issue number10
DOIs
Publication statusPublished - Oct-2020

Keywords

  • brain death
  • estradiol
  • female Wistar rats
  • heart
  • inflammation
  • INFLAMMATORY RESPONSE
  • ACTIVATION
  • APOPTOSIS
  • ESTROGEN
  • TRAUMA

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