Sex Differences in Sympathetic Responses to Lower Body Negative Pressure.

Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. Data from 17 females and 19 males, aged 19-45, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (40 mmHg and 50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs. male: 894 ± 304 min*mmHg [time*LBNP]; p = 0.003). At LBNP 40 mmHg and 50 mmHg, females had lower diastolic blood pressures (main effect of sex: p = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: p = 0.016) accompanied by a lower total vascular conductance (sex: p = 0.028; main effect of sex). Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at 40 and 50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

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Conflict of Interest and Funding Source: This research was supported by the Department of Defense (DOD) Grants W81XWH22C0004 (to C.G.C.) and W81XWH-18-2-0012 (to C.G.C.). No conflicts of interest, financial or otherwise, are declared by the authors.