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

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. Healthy young males ( = 29, 26 ± 4 yr) and females ( = 23, 27 ± 5 yr) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO (etCO ), and cerebral oxygen saturation (ScO ) were measured continuously. Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1,604 ± 68 s vs. females, 1,453 ± 78 s; = 0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO were similar between males and females throughout LBNP and at presyncope ( ≥ 0.20). Interestingly, although decreases in etCO were similar between the sexes throughout LBNP ( = 0.16), at presyncope, the %Δ etCO from baseline was greater in males compared to females (-30.8 ± 2.6% vs. -21.3 ± 3.0%; = 0.02). Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO during central hypovolemia. Tolerance and cerebral blood velocity responses to simulated hemorrhage (elicited by lower body negative pressure) were similar between male and female subjects. Interestingly, the change in etCO from baseline was greater in males compared to females at presyncope, suggesting potential sex differences in cerebral vascular sensitivity to CO during simulated hemorrhage. These findings may facilitate development of individualized therapeutic interventions to improve survival from hemorrhagic injuries in both men and women.