Insight into the mechanism by which estradiol improves organ functions after trauma-hemorrhage

Background. Recent studies have indicated that female rodents with high levels of estradiol (proestrus) have better organ functions after trauma-hemorrhage than females with low estradiol levels (estrus) or mab animals. However the precise role of estrogens in maintaining organ function after hemorrhage remains unknown. Methods. Adult female Sprague-Dawley rats were ovariectomized 14 days before the experiment to increase circulating levels of estradiol. Animals underwent laparotomy to induce tissue trauma and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume teas returned in the form of Ringer's lactate. Resuscitation was carried out with 4 times the volume of maximal bleed-out with Ringer's lactate during a period of 1 hour 17 beta-Estradiol (E2, I mg/kg body weight intravenously) with or without a specific estrogen receptor antagonist ICI 182,780 (3 mg/kg body weight intraperitoneally) was given at the beginning of resuscitation. At 24 hours after hemorrhage and resuscitation, cardiovascular and hepatocellular functions (ie, the maximal velocity and overall efficiency of indocyanine green clearance) were determined. Plasma E2 was also assayed. The effects of ovariectomy and E2 administration on uterine weight were measured in additional groups of animals. Results. The results indicate that cardiovascular and hepatocellular organ functions were significantly depressed after trauma-hemorrhage and were restored in animals receiving E2. However simultaneous administration of its specific receptor antagonist abolished the salutary effects of E2 treatment despite high circulating levels of E2. Uterine weight decreased at 14 days after ovariectomy, which was partially restored with a single dose of E2. Conclusions. Administration of 17 beta-estradiol should be considered a novel and safe adjunct for ameliorating hemorrhage-induced organ dysfunctions in ovariectomized and postmenopausal women because of their low estradiol levels.