Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure

Abstract

Introduction: 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.

Methods: Data from 17 females and 19 males, aged 19-45 yr, 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 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).

Results: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 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).

Conclusions: 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.

Figure 1.

Representative figure of mean blood pressure responses to LBNP in a male (grey) and female (black) between A. absolute LBNP stages and B. 33%, 66%, and 100% of LBNP tolerance.

Figure 2.

Tolerance to progressive LBNP in males (closed circles) and females (open circles) expressed as cumulative stress index (CSI). Females had lower tolerance to progressive central hypovolemia. Data are shown as median ± interquartile range with the circles representing individual data points. n = 19 males and 17 females.

Figure 3.

Absolute LBNP: A. burst frequency and C. burst incidence, and relative B. burst frequency, and D. burst incidence responses to LBNP in males (closed circles) and females (open circles). The number of participants, for males and females, respectively, are: Baseline: n = 19 and 17, LBNP 40: n = 19 and 17, LBNP 50: n = 19 and 13 for the absolute LBNP analyses. For the relative LBNP analysis, the number of participants for males and females, respectively, are: Baseline: n = 19 and 17, 33% = 19 and 17, 66% = 19 and 16, and 100% = 17 and 16 for the relative LBNP analyses.

Figure 4.

Change (i.e., Δ) in plasma epinephrine and norepinephrine concentrations from baseline to end LBNP in males (closed circles) and females (open circles) are depicted in the upper panels; these data are presented as median ± interquartile range. The absolute concentrations of epinephrine and norepinephrine are depicted in the lower panels, with these values presented as mean ± standard deviation.