17β-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors
Roberta Figueiredo Vieira1, Ana Cristina Breithaupt-Faloppa, Cristiano Jesus Correia
1Laboratório Cirúrgico de Pesquisa Cardiovascular, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
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 17β-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 µg/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:
17β-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). 17β-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:
17β-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.
Insights
17β-estradiol (E2) improves intestinal graft quality in brain death (BD) models. E2 treatment enhanced mesenteric perfusion and reduced tissue damage, suggesting its potential for improving small bowel donor organs.
Area of Science:
- Transplantation Science
- Endocrinology
- Vascular Biology
Background:
- Small bowel graft viability is a major challenge in organ retrieval from brain-dead donors.
- Brain death (BD) significantly compromises intestine graft quality, leading to poorer transplantation outcomes.
- 17β-estradiol (E2) has demonstrated vascular protective effects in other organs affected by BD.
Purpose of the Study:
- To investigate the potential of 17β-estradiol (E2) as a therapeutic agent to improve intestinal graft quality in a rat model of brain death (BD).
Main Methods:
- Male Wistar rats were subjected to sham operation, BD, or BD with E2 treatment.
- Mesenteric perfusion was assessed using laser-Doppler flowmetry and intravital microscopy.
- Histopathological analysis, gene and protein expression of eNOS and endothelin-1, and inflammatory markers were evaluated.
Main Results:
- E2 treatment significantly improved mesenteric microcirculatory perfusion in BD rats (67% vs 40%).
- 17β-estradiol reduced intestinal edema and hemorrhage and decreased expression of adhesion molecules like VCAM-1.
- E2 treatment led to a significant increase in endothelial nitric oxide synthase (eNOS) expression.
Conclusions:
- 17β-estradiol effectively mitigates the detrimental effects of BD on intestinal grafts, improving perfusion and reducing tissue damage.
- E2 shows promise as a therapeutic strategy to enhance the quality of small bowel grafts from deceased donors.
