## 3 Results
### Exposure to 90 s LBNP  
Exposure to \(-\)10 to \(-\)40 mmHg LBNP for 90 s was well tolerated by all subjects. No significant changes from baseline and no sex differences were detected in ABP, although females exhibited a slight decreasing trend at increasing LBNP magnitude. Minor but significant increases were detected in HR at \(-\)40 mmHg (females: 75.3 \(\pm\) 14.7 ppm; males: 69.2 \(\pm\) 14.9 BPM), with no sex differences. The full time course of the responses of NIRS variables to the 90 s exposure to different levels of LBNP is described by the average tracings of Figure 2, for both the forearm and the thigh (males and females being pooled together). It can be observed that TOI and HHb exhibited a qualitatively similar (but specular) pattern in arms and legs, consisting, after an initial transient, in an almost linear decrease in TOI and increase in HHb, with slopes increasing with the magnitude of the LBNP. Conversely, blood volume indices THI and tHb both exhibited opposite patterns: a decrease in the arm, starting immediately with application of the stimulus, completing in 10-20 s and then remaining stable until the end of the stimulus, and an increase in the leg, initially rapid and later slow, not achieving a stable level within the 90 s duration of the stimulus. Also in this case, the effects were related to the magnitude of the stimulus. Comparison of responses for male and females at the different LBNP magnitudes, along with statistical significance, is reported in Figure 3. It can be observed that a main effect of pressure is exhibited by all NIRS variables, while a significant dependence on sex results only for TOI and HHb slopes and not for blood volume changes. Note that the TOI and HHb slopes were calculated over the time interval following the rapid blood volume shift, where the variables exhibit a mostly linear trend.  
Figure 2: Averaged response of NIRS parameters recorded from the forearm (**A**) and the thigh (**B**), during 90 s exposure to LBNP of \(-10\), \(-20\), \(-30\), \(-40\) mmHg. Vertical dashed lines indicate the start and the end of the LBNP stimulus; vertical colored bands indicate where the measurements were taken to quantify average effects and slopes (Figure 3), the yellow band indicating the baseline. TOI: tissue oxygenation index; HHb: deoxy-hemoglobin concentration; THI: tissue hemoglobin index; tHb: total hemoglobin concentration. The THI tracings were normalized to baseline; HHb and tHb: baselines were set to 0. The number of subjects (n) includes males and females pooled together.  
Figure 3: Average of LBNP on systemic variables (**A**,**B**) and local NIRS variables from the forearm (**C**,**E**,**G**,**I**) and the thigh (**D**,**F**,**H**,**J**) in males and females. MAP: mean arterial pressure; HR: heart rate; TOI: tissue oxygenation index; HHb: deoxy-hemoglobin concentration; THI: tissue hemoglobin index; tHb: total hemoglobin concentration. Different colors are associated with the different pressure levels, while the black and gray lines indicate males and females, respectively. Main effects and interaction are reported in text form and post hoc tests are reported with symbols (#: \(p<0.001\); \({}^{*}p>0.05\)), the color identifying the pressure level considered in the comparison, e.g., a red asterisk over the green dot indicates a significant difference between the red (40 mmHg) and green (20 mmHg) conditions. If # and \({}^{*}\) are within black (gray) square brackets they refer specifically to the male (female) group. Otherwise, they refer to the whole group (males + females). The total number of subjects (n) is also distinctly specified for males (M) and females (F).