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

Background. Recent studies have indicated that female rodents with high lev els of estradiol (proestrus) have better organ functions after trauma-hemor rhage than females with low estradiol levels (estrus) or mab animals. Howev er the precise role of estrogens in maintaining organ function after hemorr hage remains unknown. Methods. Adult female Sprague-Dawley rats were ovariectomized 14 days befor e the experiment to increase circulating levels of estradiol. Animals under went laparotomy to induce tissue trauma and were then bled to and maintaine d at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-ou t volume teas returned in the form of Ringer's lactate. Resuscitation was c arried out with 4 times the volume of maximal bleed-out with Ringer's lacta te during a period of 1 hour 17 beta-Estradiol (E2, I mg/kg body weight int ravenously) 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, cardiovascul ar and hepatocellular functions (ie, the maximal velocity and overall effic iency of indocyanine green clearance) were determined. Plasma E2 was also a ssayed. 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 res tored in animals receiving E2. However simultaneous administration of its s pecific 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 nov el and safe adjunct for ameliorating hemorrhage-induced organ dysfunctions in ovariectomized and postmenopausal women because of their low estradiol l evels.