Assessment of Ethynylestradiol-3-sulfate on Coagulation, Metabolism and Survival in Pigs with Traumatic Hemorrhage.

Abstract

The beneficial effects of estrogens on survival from hemorrhage have been suggested in some preclinical models. This study investigated the effects of ethynylestradiol-3-sulfate (EE-3-S) on coagulation, metabolism and survival in pigs following traumatic hemorrhage. Twenty-six pigs were randomized into: normal saline group (NS, n = 10), EE-3-S group (EE-3, n = 11) groups, and no resuscitation group (NR, n = 5). Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and a 10 min shock period. Afterwards, pigs were resuscitated with a small volume of either NS alone (4 ml/kg) or EE-3-S with NS (1 ml/kg at concentration of 1 mg/ml, plus NS solution of 3 ml/kg). Pigs in NR group were not resuscitated with any fluid. All pigs were then monitored for 6 hours or until death, with hemodynamics and survival times recorded. Blood samples were taken during the study for measurements of oxygen metabolism (oxygen delivery, extraction, and consumption) and coagulation function (using Rotem® with Extem reagents). All baseline measurements were similar among the 3 groups. In the NS group, femur fracture and hemorrhage immediately reduced mean arterial pressure (MAP, 74 ± 3 mmHg to 44 ± 4 mmHg) and increased heart rate (97 ± 5 bpm to 218 ± 14 bpm, both p < 0.05). Similar changes in MAP and heart rate were observed in the EE-3 and NR groups. There were no differences observed in changes of Rotem® measurements or oxygen metabolism among the groups during the study. At 6-hour, 4 pigs in NS, 4 pigs in EE-3-S, and 2 pigs in the NR group survived to the end of the study. The mean survival times were similar among the NS (212 ± 43 min), EE-3 (212 ± 39 min) and NR (223 ± 63 min) groups (p = 0.9845). Following severe traumatic hemorrhage, hypotensive resuscitation with EE-3-S did not impact coagulation, metabolism, or survival in pigs.Study type: laboratory animal study. N/A.