Sex Differences in the Oxidative Stress and Inflammation Response During and After Simulated Hemorrhage in Humans

Introduction: Hemorrhage (i.e., massive blood loss) induces an oxidative stress and inflammatory response that can persist even following hemostasis and resuscitation. 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 simulated hemorrhage. Methods: Healthy human subjects (10F; 10M) participated in a presyncopal lower body negative pressure (LBNP) protocol (simulating hemorrhage). Stroke volume was estimated as a marker of central hypovolemia (indexed to body surface area). Venous blood samples were collected at baseline, at the onset of presyncope, and 60-min into recovery ("resuscitation"). Oxidative stress and inflammation responses were assessed via measurement of circulating F2-Isoprostanes (F2-IsoP) and interleukin (IL)-6 and IL-10. Results: LBNP tolerance time was similar between male and female subjects (Males, 1592±124 s vs. Females, 1437±113 s; P=0.37), and stroke volume index decreased by a similar magnitude at presyncope (Males, -50.2±6.3% vs. Females, -49.4±3.2%; P=0.87). There was no effect of time or sex on the %Δ [F2-IsoP] during or after LBNP (P≥0.12). However, male subjects exhibited a greater increase in both the %Δ [IL-6] and %Δ [IL-10] compared to female subjects at the 60-min recovery time point (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). Conclusion: These data suggest there may be a sex difference in the inflammatory response to blood loss and subsequent fluid resuscitation.