17 beta-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors

Autor(es)

Vieira, Roberta Figueiredo ^[1] ; Breithaupt-Faloppa, Ana Cristina ^[1] ; Correia, Cristiano Jesus ^[1] ; Armstrong, Jr., Roberto ^[1] ; Coutinho-e-Silva, Raphael dos Santos ^[1] ; Ferreira, Sueli Gomes ^[1] ; Moreira, Luiz Felipe Pinho ^[1] ; Sannomiya, Paulina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Inst Coracao Hosp Clin, Lab Cirurgico Pesquisa Cardiovasc, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TRANSPLANTATION; v. 104, n. 9, p. 1862-1868, SEP 2020.
• Citações Web of Science: 0

Resumo

Background. Intestine graft viability compromises retrieval in most brain-dead donors. Small bowel transplantation is a complex procedure with worse outcomes than transplantation of other abdominal organs. The hormone 17 beta-estradiol (E2) has shown vascular protective effects in lung tissue of brain death (BD) male rats. Thus, estradiol might be a treatment option to improve the quality of intestinal grafts. Methods. Male Wistar rats were divided into 3 groups (n = 10/group): rats that were trepanned only (sham-operated), rats subjected to rapid-onset BD, and brain-dead rats treated with E2 (280 mu g/kg, intravenous) (BD-E2). Experiments performed for 180 minutes thereafter are included: (a) laser-Doppler flowmetry and intravital microscopy to evaluate mesenteric perfusion; (b) histopathological analysis; (c) real-time polymerase chain reaction of endothelial nitric oxide synthase (eNOS) and endothelin-1; (d) immunohistochemistry of eNOS, endothelin-1, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 expression; and (e) ELISA for cytokines and chemokines measurement. Results. 17 beta-Estradiol improved microcirculatory perfusion and reduced intestinal edema and hemorrhage after BD. The proportions of perfused small vessels were (mean +/- scanning electron microscope) BD rats (40% +/- 6%), sham-operated rats (75% +/- 8%), and BD-E2 rats (67% +/- 5%) (P= 0.011). 17 beta-Estradiol treatment was associated with 2-fold increase in eNOS protein (P< 0.0001) and gene (P= 0.0009) expression, with no differences in endothelin-1 expression. BD-E2 rats exhibited a reduction in vascular cell adhesion molecule 1 expression and reduced cytokine-induced neutrophil chemoattractant 1 and interleukina-10 serum levels. Conclusions. 17 beta-Estradiol was effective in improving mesenteric perfusion and reducing intestinal edema and hemorrhage associated with BD. The suggestion is that E2 might be considered a therapy to mitigate, at least in part, the deleterious effects of BD in small bowel donors. (AU)

• Processo FAPESP: 16/13632-3 - AVALIAÇÃO DOS EFEITOS DO 17beta-ESTRADIOL SOBRE AS ALTERAÇÕES MICROCIRCULATÓRIAS INDUZIDAS PELA MORTE ENCEFÁLICA EM RATOS MACHOS
• Beneficiário: Paulina Sannomiya
• Modalidade de apoio: Auxílio à Pesquisa - Regular