Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults

Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 +/- 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO2) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F-2-isoprostanes (F-2-IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Delta) in SV, ranged from 27 to 74% (53.5 +/- 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 +/- 2.6% (P < 0.001 vs. pre-LBNP baseline). F-2-IsoP increased by 28.5 +/- 11.6% (P = 0.05) from baseline (24 +/- 2 pg/mL) to presyncope (29 +/- 3 pg/mL). The increase in F-2-IsoP was not associated with %Delta SV (r = 0.21, P = 0.46), %Delta MAP (r = 0.05, P = 0.86), %Delta SmO2 (r = 0.05, P = 0.90), or the maximum level of LBNP attained (r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress.