The Effects Of Ethynylestradiol‐3‐Sulfate (EE‐3‐S) On Blood Volume and Organ Function In Pigs With Severe Traumatic Hemorrhage

Abstract

IntroductionThe beneficial effects of estrogens to improve survival from hemorrhage have been suggested in experimental studies of rodents and minipigs, as well as some clinical observations. However, the underlying possible protective mechanisms remain unclear. This study investigated the effects of ethynylestradiol‐3‐sulfate (EE‐3‐S) on blood volume and organ functions in pigs following severe traumatic hemorrhage and hypotensive resuscitation.MethodsTwenty anesthetized and instrumented pigs were randomized into saline (n=10) and EE‐3‐S(n=10) groups. Femur fracture was performed in each pig's left leg, followed byhemorrhage of 55% of estimated blood volume and 15 min shock period. Afterwards, pigs were hypotensively resuscitated with a small volume of saline(4 ml/kg) or EE‐3‐S (1 mg/kg at concentration of 1 mg/ml, plus 3 ml saline/kg). Indocyanine green dye (5 ml of 1 mg/ml) was injected before femur fracture and hemorrhage and 15 min after EE‐3‐S administration with serial blood samples taken accordingly to determine changes of blood volume. Pigs remained anesthetized and were monitored for 6 h or until death, and blood samples were taken every 2 h for measurements of blood gases and chemistry.ResultsAll baseline measurements are similar between the two groups. Femur fracture and hemorrhage reduced mean arterial pressure to 54±6% of baseline values and reduced blood volume from 104±4 ml/kg to 67±4 ml/kg (both p<0.05) and reduced Hctfrom 31±1% to 28±1% in the saline resuscitated group. Similar reductions were observed with EE‐3‐S resuscitation in blood volume (from 109±4 ml/kg to 68±3 ml/kg, p<0.05) and Hct (30±1% to 27±1%, p<0.05). Compared to baseline value, creatinine, asparate aminotransferase (AST), and lactate dehydrogenase(LDH) were elevated at 6 h or death from 1.3±0.1 mg/dL to 3.1± 0.2 mg/dL, 33±3 U/L to 98±16 U/L, and 450± 55 U/L to 645±122 U/L, respectively (all p<0.05). Similar increases were observed in creatinine (1.4±0.2 mg/dL to 2.9±0.1 mg/dL), AST (32±3 U/L to 135±46 U/L) and LDH (450±35 U/L to 501±95 U/L) in the EE‐3‐S group (all p<0.05). Survival time was similar between the saline (212±43 min) and EE‐3‐S (212±39 min) groups.ConclusionsFollowing severe traumatic hemorrhage and small volume resuscitation, administration of EE‐3‐S did not affect blood volume, organ function or short term survival in this model.Support or Funding InformationUS Army Medical Research and Materiel CommandThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.