**4. Discussion**

The value of the skin microvascular bed as an object of research for identifying the patterns of the cardiovascular system functioning is under discussion nowadays. In a review work, based on the results of LDF amplitude–frequency wavelet analysis, Martini R. and Bagno A. showed that changes in the parameters of the skin microcirculation are detected in the widest range of diseases [24]. This includes studies of diabetes complications [25], peripheral arterial disease [26] and arterial hypertension [27] among other conditions.

It is known that the microvascular bed of the skin is not subject to baroreflex regulation [28,29], and the results we obtained on the forearm are very interesting. During the transition to orthostasis, when the measurement area was below the height of the heart, we noted decreases in the amplitudes of endothelial, neurogenic and myogenic vasomotions. A decrease in the vasomotions' amplitude indicates a decrease in the lumen size of resistive precapillary arterioles, which can be regarded as an increase in the vascular tone. It can be assumed that a decrease in the lumen of resistive precapillary arterioles leads to a decrease in the amplitude of cardiac oscillations in microvessels, which, in turn, indicates a decrease in arterial blood flow to the capillaries. A decrease in the amplitude of cardiac oscillations at the level of precapillary arterioles can be caused by several mechanisms: (1) An increase in hydrostatic pressure in the venular link of the vascular bed amidst the difficulty in the blood outflow from the capillaries leads to an increase in the capacitive vessels tone, which, through the mechanisms of venulo-arteriolar communication, can lead to an increase in the tone of the bringing arterioles [30]. (2) Activation of the sympathoadrenal system due to weakening of the depressor effects on it from the baroreceptors of the carotid sinus. Amidst that, the subjects showed a significant increase in diastolic blood pressure and heart rate. We did not find a significant correlation between these parameters, which may have been due to a small sample size, but it can be assumed that there is a relationship between the amplitude of vasomotions of the tone-forming mechanisms of skin microvessels and the level of blood pressure. If this hypothesis is correct, then the LDF technique can be a useful additional tool for interpreting the results of 24-h blood pressure monitoring when patients are in an upright position for most of the day, and for monitoring the functional state of resistive skin microvessels when prescribing antihypertensive therapy.

When the head is lowered 15° below the horizontal line, the measurement point on the forearms is slightly above the heart level, which does not affect the functional state of the tone-forming regulatory mechanisms of skin microcirculation in the upper extremities. Amidst this, there is a significant increase in the amplitude of the cardiac oscillations, which can be explained by the opposite mechanisms observed in orthostasis: (1) the precapillary arterioles' tone is restored through the mechanisms of venulo-arteriolar communication against the background of a decrease in pressure in the venous vessels; (2) a decrease in the activity of the sympathoadrenal system amidst the restoration of the depressor activity of the carotid sinuses. An increase in the arterial blood inflow into the microvasculature is accompanied by a significant increase in the level of tissue perfusion (Figure 3a). For the lower extremities, a change in body position leads to a decrease in the amplitude of cardiac oscillations (a decrease in inflow), and a corresponding decrease in the level of tissue perfusion without changing the activity of tone-forming mechanisms at the level of resistive precapillary arterioles. This is most likely due to regional features of the tissue perfusion regulation of the skin in the legs and is of a compensatory nature aimed at maintaining nutritive blood flow in conditions of decreased tissue perfusion. In a nonphysiological position for the legs, when they are above the heart, the outflow of venous blood is significantly facilitated, but the perfusion pressure decreases. Amidst this, we see an insignificant tendency towards a decrease in the amplitude of neurogenic and myogenic

vasomotions (increased tone), which can also be regarded as a compensatory response aimed at maintaining perfusion pressure in the skin capillaries.

The results of the study of skin perfusion in the forehead can be of particular interest in connection with the brain's blood supply. It is known that the scalp receives nutrition from the external carotid artery system, and only the skin of the forehead is supplied with blood from the a.supratrochlearis and a.supraorbitalis, which are the final branches of the supraorbital arteries that are part of the internal carotid artery system [31]. The researchers' interest in the basin of the a.supraorbitalis is due to the fact that disorders of microcirculatory blood flow in the eye area (fundus and bulbar conjunctiva) are associated with various variants of cerebral circulatory disorders [32–34]. As was shown in the pilot study [35], the nature of skin microcirculation in the forehead significantly differs in the level of skin perfusion and in the activity of regulatory mechanisms, depending on the side and volume of ischemic brain damage, and during thrombolytic therapy, these parameters showed significant changes.

The higher level of average blood perfusion in skin of the forehead, relative to the skin of the upper and lower extremities, and the stability of cutaneous blood perfusion in any position of the body (Figure 5a), draw attention. This may indicate a high potential of the mechanisms of autoregulation of cerebral blood flow. Significant changes in the regulatory mechanisms at the level of precapillary arterioles are observed only in orthostasis and are expressed in an increase of amplitude of neurogenic and myogenic vasomotations. When the head is higher than the heart, the neurogenic and myogenic mechanisms of microvascular tone-forming are reduced.

In the Trendelenburg position, when not only the outflow of venous blood from the head is hindered, but also the pressure in the arterial bed increases, the functional state of the tone-forming mechanisms changes in a very wide range. We assume that this is due to the high potential of the mechanisms of regulation of cerebral hemodynamics. For the tone-forming mechanisms of microcirculation regulation (Ae, An and Am), changing their functional activity according to the principle of positive and negative responses, modulates the volume and speed of arterial blood flowing to the capillaries (Ac) to the optimal values for transcapillary exchange in the vascular volume at the time, and in our study—depending on the position of the body in space.

The facial skin, as an object of research, is also interesting due to its features of innervation. The system of innervation of skin microvessels is mainly represented by somatic sensitive (afferent) and vegetative sympathetic (efferent) systems of regulation. The direct involvement of the parasympathetic nervous system in the regulation of cutaneous microvessels is considered proven only for the skin of the face [32,36]. Thus, the study of microcirculatory blood flow in the area of the facial skin opens up opportunities for studying almost all mechanisms of neurogenic control of the vasomotor activity of resistive microvessels at the opposite end to the heart pole of the grea<sup>t</sup> circle of blood circulation [37].
