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

Abstract

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.

Comparison of acute kidney injury following brain death between male and female rats

“…In relation to inflammation and function, both sexes suffer from deterioration due to BD and IPK time. Since the therapeutic with 17β-estradiol has been effective in protecting several organs from deleterious effects triggered by BD [ 18 , 19 , 37 , 38 , 39 ], further studies with ex vivo perfusion may incorporate 17β-estradiol in the perfusate solution as a prospective therapy to improve the renal graft of both sexes for transplantation.…”

Sex differences in the coagulation process and microvascular perfusion induced by brain death in rats

“…We observed thrombus formation in male vessels through intravital microscopy, confirming that this occurrence might be responsible for organ hypoperfusion observed after BD. It is important to mention that the treatment of male BD rats with estradiol is able to restore the microcirculatory perfusion [31].…”