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

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.