The impact of acute central hypovolemia on cerebral hemodynamics: does sex matter?

Abstract

Trauma-induced hemorrhage is a leading cause of disability and death due, in part, to impaired perfusion and oxygenation of the brain. It is unknown if cerebrovascular responses to blood loss are differentiated based on sex. We hypothesized that compared to males, females would have reduced tolerance to simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and this would be associated with an earlier reduction in cerebral blood flow and cerebral oxygenation. Methods: Healthy young males (n=29, 26±4 y) and females (n=23, 27±5 y) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO2 (etCO2), and cerebral oxygen saturation (ScO2) were measured continuously. Results: Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1604±68 s vs. females, 1453±78 s; P=0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO2 were similar between males and females throughout LBNP and at presyncope (P≥0.20). Interestingly, while decreases in etCO2 were similar between the sexes throughout LBNP (P=0.16), at presyncope, the %Δ etCO2 from baseline was greater in males compared to females (-30.8±2.6% vs. -21.3±3.0%; P=0.02). Conclusion: Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO2 responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO2 during central hypovolemia.

Determinants of orthostatic cerebral oxygenation assessed using near-infrared spectroscopy

“…Sex was not significantly associated with any of the other O 2 Hb and TSI drop and recovery parameters. A previous study also did not find sex differences between TSI drop during lower body negative pressure, which is in line with the present results, but did not assess O 2 Hb differences (Rosenberg et al, 2021). The significant role of sex in O 2 Hb initial drop amplitude found in the present study may suggest a higher cerebral autoregulation activity immediately after standing up in females, attenuating the initial orthostatic cerebral oxygenation drop.…”

Influence of sex on the reliability of cerebral blood velocity regulation during lower body negative pressure and supine cycling with considerations of the menstrual cycle

“…Progressive LBNP has been performed previously to simulate blood loss and has demonstrated the ability to cause symptoms of presyncope (Rickards et al 2015, Rosenberg et al 2021. However, despite the increasing knowledge surrounding the functioning of the cerebrovascular system while undergoing LBNP, a limitation of previous research is the lack of inclusion of female participants (Kennedy et al 2022).…”

“…The peak increase in CBF occurs at ∼50%-80% of an individual's maximal oxygen uptake (VO 2max ) due to an elevation in circulating carbon dioxide, which has been termed hyperpnea-induced vasodilation (Ogoh et al 2009, Smith andAinslie 2017). As previously mentioned, LBNP can be used to stimulate blood loss (Rickards et al 2015, Rosenberg et al 2021, therefore acting as a modality to challenge the cerebrovasculature by driving blood from the upper extremities towards the lower extremities.…”

Sex Differences in Sympathetic Responses to Lower Body Negative Pressure

“…T rauma-induced hemorrhage contributes to early death in both civilians and military personnel (1)(2)(3). Most (4)(5)(6), but not all (7), studies show that females have a reduced tolerance to central hypovolemia (a simulation of hemorrhage via lower-body negative pressure (LBNP)) compared with males, but the mechanism(s) responsible for these differences remain unknown. Evidence suggests that females have higher death rates on the battlefield compared with males (8).…”

“…Perhaps the reason for these heightened heart rate responses is due to females having a lower stroke volume at equal levels of LBNP, resulting in a need for a higher heart rate to maintain (or minimize the decrease in) cardiac output (6,12). Despite such sex-related differences, there are mixed results on the effect of LBNP on mean arterial blood pressure responses between sexes (4,6,7,11,12).…”