## 4 Discussion
### Analysis of Time Courses Reveals Blood Volume and Oxygen Changes  
The full time course of the hemodynamic responses to LBNP has rarely been reported; knowledge of time courses is, however, necessary to disentangle the effects of coexisting \begin{table}
\begin{tabular}{c c c} \hline \hline
**District** & **NIRS Parameters** & **Pearson’s R** \\ \hline \multirow{4}{*}{**Forearm**} & TOI slope & 0.43 \\  & HHb slope & 0.59 \\  & THI delta & 0.94 \\  & thb delta & 0.91 \\ \hline \multirow{4}{*}{**Thigh**} & TOI slope & 0.97 \\  & HHb slope & 0.93 \\ \cline{1-1}  & THI delta & 0.75 \\ \cline{1-1}  & thb delta & 0.52 \\ \hline \hline \end{tabular}  
* TOI: tissue oxygenation index; HHb: deoxy-hemoglobin concentration; THI: tissue hemoglobin index; tHb: total hemoglobin concentration.  
\end{table} 
Table 1: Repeatability test of measurements related to 90 s, \(-30\) mmHg stimuli. changes in blood volume and blood flow. First of all, it is possible to observe that spatially resolved spectroscopy (SRS) and BL parameters provide qualitatively similar patterns of response (THI parallels HHb, and TOI is specular to HHb) suggesting that skin and muscle tissues do not respond in a conflicting way. In fact, it has been shown in several contexts that SRS parameters focus the measurement at depth while BL ones are affected by both cutaneous and deep (brain or muscular) circulation and that a different response from superficial and deep tissues may result in different or even opposite changes in BL and SRS variables [12; 13; 23]. It is reasonable to expect that muscles and skin exhibit similar passive and myogenic responses to blood pressure while the reflex sympathetic response to mild hypovolemic stimuli mostly concerns the muscular circulation [24]. The rapid blood volume change is detected by tHb and THI (Figures 2 and 4): as expected a decrease occurs in the arm, as a consequence of lowered central venous pressure [2; 5; 25], and an increase occurs in the leg, as a consequence of vessel dilatation stimulated by the increased transmural pressure [1; 26]. However, while in the arm it completes within 15-20 s, in the leg it continues at a slower rate for more than 5 min, documenting the occurrence of a slow stress relaxation of vessel walls. The relevance of stress relaxation was pointed out with model fitting the hemodynamic response to passive head-up tilt [27]. In the cited study a time constant of 30 s was assumed for this phenomenon, based on previous studies on animal models. The present results suggest a slower time course (with a time constant of about 90 s), as can be roughly estimated from the THI and tHb recordings of Figure 4 (right). However, it must be reminded that the present measurements are representative of a small sample volume, not the entire lower limb, and that the largest and fastest volume increase is exhibited by the large veins rather than smaller vessels within the muscle tissue [28]. After the initial transient, the effect of vasoconstriction and blood flow reduction may be analyzed. To this aim, the attention has been focused on TOI and HHb whose slopes are indicative of a perfusion/metabolism mismatch [8], while O2 Hb was not considered due to its larger dependence on confounding factors, such as the cutaneous circulation [14]. Since blood pressure is substantially unchanged, as well as the metabolism of resting limbs, the negative TOI and positive HHb slopes reveal a reduction in blood flow, as likely induced by the sympathetically mediated increase in vascular resistances. Notably, this effect is LBNP-dependent and occurs in both arms and legs. It can be observed that this slow TOI decrease (and HHb increase) is much slower in the leg than in the arm. This is likely due to the longer time required for the deoxygenated blood to invade the enlarged venous compartment of the legs as compared to the emptied compartment of the arms, as well as to a hyperemic response affecting the lower limbs (see below).