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.

• Authors: Roberta Figueiredo Vieira, Ana Cristina Breithaupt-Faloppa, Cristiano Jesus Correia, Roberto Armstrong Jr, Raphael Dos Santos Coutinho-E-Silva, Sueli Gomes Ferreira, Luiz Felipe Pinho Moreira, Paulina Sannomiya
• Journal: Transplantation (Transplantation) Vol. 104 Issue 9 Pg. 1862-1868 (09 2020) ISSN: 1534-6080 [Electronic] United States
• PMID: 32345867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Estradiol

Topics

• Animals
• Brain Death (physiopathology)
• Cytokines (blood)
• Estradiol (pharmacology)
• Gastrointestinal Hemorrhage (prevention & control)
• Intestine, Small (pathology, transplantation)
• Male
• Microcirculation (drug effects)
• Perfusion
• Rats
• Rats, Wistar
• Splanchnic Circulation (drug effects)
• Tissue Donors