Effects of Resuscitation Adjuncts on Indices of Inflammation and Oxidant Stress in Tissues from Swine Subjected to Traumatic Hemorrhage

In the absence of blood products, pre‐hospitaluse of small volume adjuncts to enhance crystalloid resuscitation has beenproposed to reduce inflammation and improve outcomes in the bleeding traumapatient. However, the most effective drugs for this purpose remain underintense investigation. The present study investigated the effects of Poloxamer‐188(P‐188), a surfactant with membrane resealing activity andethynylestradiol‐3‐sulfate (EE‐3‐S), an estrogen compound, on indices ofinflammation and oxidant stress in tissues from swine subjected to traumatichemorrhage. Both compounds are suggested to have anti‐inflammatory andpotentially anti‐oxidant activity. Methods Thirty anesthetized and instrumented pigs weresubjected to a left leg femur fracture followed by hemorrhage of 55% of the estimatedblood volume and a 15 min shock period. Pigs were then randomized into 3 groups(n=10/group) and resuscitated with equal small total volumes of normal saline (NS;4ml/kg) alone or NS containing P188 (200 mg/kg) or EE‐3‐S (1 mg/kg). Animalswere continuously monitored under anesthesia for 6h or until death. At death oreuthanasia, samples of liver, kidney, lung, heart and jejunum were flash‐frozenand stored at −80°C until assayed for antioxidant status, antioxidantenzyme activities and select cytokines. Results Hemorrhage reduced mean arterial pressure to 54±6%of baseline levels (p<0.05). In all tissues, total antioxidant status, reduced glutathione and antioxidant enzyme activities were similar amonggroups. In lung, however, nitric oxidelevels were 28% lower in the P‐188 treated than NS group (p<0.05). In liver, levels of IL‐1β, TNF‐α and IL‐6 were 25–30% lower in the P‐188 and EE3‐S treatedthan NS resuscitated swine (p<0.05), whereas IL‐10 levels were similar amonggroups. No statistically significant differences in cytokine concentrationswere observed in kidney, lung, heart or jejunum among the groups. Conclusions These data suggest that in this swine model oftraumatic hemorrhage and small volume resuscitation with crystalloid containingP‐188 or EE3‐S, any anti‐inflammatory activity was only observed in the liver. Support or Funding Information US Army Institute of Surgical Research, San Antonio, TX 78234 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .