Sex Differences in Oxidative Stress and Inflammation Responses During and After Simulated Hemorrhage




Barnes, Haley J.


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Hemorrhage (i.e., massive blood loss) induces an oxidative stress and inflammatory response that can persist even following hemostasis and resuscitation. Premenopausal females exhibit a survival advantage following hemorrhage compared to young males. In this study, we hypothesized that young males would elicit a greater oxidative stress and inflammatory response compared to young females, both during and after a simulated hemorrhage via lower body negative pressure (LBNP). Young, healthy human subjects (10F; 10M) participated in a stepwise-LBNP protocol to presyncope. Venous blood samples were collected at baseline, presyncope, and 1-h into recovery (i.e., following "resuscitation"). The oxidative stress response was assessed via circulating F2-isoprostanes (F2-IsoP) using gas chromatography-negative ion chemical ionization-mass spectrometry. The inflammatory response was assessed via circulating tissue necrosis factor-α (TNF-α), C-Reactive Protein (CRP), thymus and activation-regulated chemokine (TARC), and interleukin (IL)-5, IL-6, IL-7, and IL-10, using a MSD® Multiplex assay. LBNP tolerance time was similar between male and female subjects (Males, 1592±124 s vs. Females, 1437 ± 113 s; P = 0.37). There was no effect of time or sex on the absolute or relative change in F2-IsoP during or after LBNP (P ≥ 0.12). However, male subjects exhibited a greater pro-and anti-inflammatory response during and after LBNP compared to female subjects (Notable markers at 1-h recovery compared to baseline, IL-6: Males, 101.4 ± 138.9% vs. Females, 12.3 ± 34.0%, P = 0.06; IL-10: Males, 71.1 ± 133.3% vs. Females, -2.2 ± 11.8%; P = 0.06). These data suggest that there may be a potential sex difference in the inflammatory response to simulated hemorrhage.