Parameters of Microcirculation in Both Sexes at Different Ages

We have used laser Doppler flowmetry with wavelet analysis of the amplitude–frequency spectrum of blood flow oscillations to investigate the microcirculation and the mechanisms of its control in both sexes at different ages: junior school age, adolescence, and preadult age. It was shown that adolescents (both boys and girls) had more intense tissue perfusion and root-mean-square deviation of microcirculation as compared with junior school age. We observed an increase in the basal indexes of microcirculation in adolescents, which is caused by the activation of regulatory processes. In preadult girls, the microcirculatory flow index (MFI) was lower compared to adolescent girls; in preadult boys, MFI is higher compared to adolescent boys. It probably results from redistribution of influence between regulatory mechanisms. The analysis of the amplitude–frequency spectrum of preadults shows a decrease in oscillation amplitudes in all active and passive oscillation ranges compared to adolescents. Thus, we have detected the differences in microcirculation parameters and in the effects of active and passive regulatory factors of microcirculation. The findings are indicative of certain age-related changes in the microcirculation system.     

Phase synchronization of skin blood flow oscillations in humans under asymmetric local heating

The hypothesis is proposed that an external local stimulus may cause a change in the phase relationships of oscillations in the peripheral skin blood flow of contralateral extremities. To test this assumption, the wavelet phase coherence of skin blood flow oscillations of the left and right forearms of 18 healthy volunteers of both sexes at rest and in response to unilateral local heating was investigated. An area of the skin of the left forearm was exposed to heat and the native blood perfusion in an area of the skin of the right forearm was recorded simultaneously. It was shown that an asymmetric local change of skin perfusion led to a significant change in the phase relationships of the blood flow oscillations in all the analyzed frequency ranges. A significant reduction of phase synchronization of oscillations of skin blood flow in the range of endothelial, neurogenic, and myogenic activity, as well as in the range of respiratory rhythm was revealed. In contrast, in the range of the cardiac rhythm, a significant increase in phase synchronization of the oscillations of the blood flow of contralateral skin areas of the forearm was detected.     

Blood flow oscillations at a frequency of about 0.1 Hz in skin microvessels do not reflect the sympathetic regulation of their tone

Wavelet analysis of blood flow oscillations recorded with laser Doppler flowmetry in finger glabrous skin microvessels was carried out in 82 subjects with different variations in the syndromes of hand and foot sympathectomy and denervation. As distinct from the 0.02–0.046-Hz (about 0.03–0.04 Hz) blood flow oscillations in skin microvessels of sympathetic thermoregulatory origin, no relationship was found between the presence of 0.07–0.015 Hz (about 0.1 Hz) vasomotions in the wavelet spectrum and intactness of sympathetic innervation in the tissue region. The use of the myogenic band oscillation parameters, in particular, the amplitudes of vasomotions, for assessing the state of sympathetic thermoregulatory innervation determining the neurogenic tone of skin microvessels is not physiologically correct. The influence of local environmental factors on the vasomotion parameters confirms their local origin. The local perfusion pressure value significantly influenced the amplitude but not the frequency of vasomotions. The amplitude dominance of vasomotions was observed upon a decrease in perfusion pressure, whereas a marked increase in perfusion pressure or venous congestion resulted in a sharp depression of their amplitudes. Under the sympathectomy conditions, the oscillatory dynamic component of the arteriolar myogenic tone in the glabrous skin of the extremity acral zones is involved in the blood flow’s autoregulation. The presence of fine sensory fibers is necessary to carry out the dynamic autoregulation of the blood flow. Sensory nonmyelinated fibers and the trophic neuropeptides secreted by them not only initiate independent oscillations in the low-frequency (0.047–0.069 Hz) myogenic band, but also contribute to the normalized amplitudes of vasomotions being increased. At the same time, no appreciable influence of the sympathetic vasomotor activity and the corresponding influence of catecholamines on the amplitude and frequency of vasomotions was observed.     

The estimation of microcirculation state in cerebrovascular disorders by data of laser Doppler flowmetry and hemorheological parameters

The study was aimed to evaluate microvascular blood flow and theological blood properties in healthy volunteers (n = 27) and patients with cerebral accident (n = 30). To study cutaneous blood flow we used the multifunctional laser analyzer of blood microcirculation LAKK (LAZMA, Moscow) with spectrophotometric channel and wavelet analysis of blood flow oscillations. Viscosity of the whole blood, plasma, RBC aggregability and deformability were assessed. Results: microcirculation index was by 25% (p < 0.05) lower in patients compared to the control group. Computing amplitude-frequency range of blood flow oscillations revealed notable changes in the blood flow regulation mechanisms under cerebrovascular accident: the amplitudes of all active rhythms (endothelial, neurogenic and myogenic ones) were increased. In spite of such activization of regulatory mechanisms, aimed to keep essential blood supply to tissue, index of specific oxygen consumption by tissue was decreased by 21% (p < 0.05) under cerebrovascular disorders. Blood rheological properties in patients group were impaired compared to the healthy group: blood viscosity was increased because of elevated plasma viscosity, increased RBS aggreagation and decreased erythrocyte deformability. Thus, our results demonstrated the decrease of tissue perfusion, activization of vasodilating mechanisms, impaired blood rheology and the decrease of oxygen supply to tissue in patients with cerebrovascular accident. Statistical analysis revealed a number of significant correlations between the hemorheological parameters and passive rhythms of microcirculation in norm. In patients blood viscosity correlated to the amplitude of active regulatory rhythms (endothelial, neurogenic and myogenic oscillations). Close interralations between rheological and microcirculation parameters testified the important role of hemorheological factors in maintenance of microvascular blood flow and oxygen delivery to tissue.     

Assessment of the changes in regulatory systems of human's skin blood flow during local heating

The mechanisms of thermal regulation of skin blood flow during local heating to 35, 40 and 45 'C have been studied by the method of laser Doppler flowmetry in healthy volunteers. To estimate the state of microvascular bed the continuous wavelet-transform spectral analysis has been used. The amplitudes of fluxmotions in the range of blood flow active modulation significantly increase during local heating to 35 degrees C. The amplitudes of blood flow oscillations in the ranges of cardiorhythm and respiratory rhythm increase during local heating to 40 degrees C. The high amplitude oscillations in the range of myogenic activity are maintained. The amplitude of oscillations in the range of endothelial activity distinctly decreases and the oscillations in the range of neurogenic activity are inhibited. Local heating to 45 degrees C results in a significant decreasing of the oscillation amplitudes in the range of myogenic activity, and the amplitudes of cardio- and respiratory spectral components amount to their peak values among the temperatures of local heating under study.     

Age-related differences in the dynamics of the skin blood flow oscillations during postocclusive reactive hyperemia

Age-related changes in peripheral microcirculation were studied using laser Doppler flowmetry in 60 apparently healthy subjects. The response of microcirculation to short-term ischemia was studied using the occlusion test. Changes in the amplitude of the peripheral blood flow oscillations were determined using time-amplitude analysis based on continuous adaptive wavelet filtration. The oscillation amplitude in the frequency range of the heart rate was found to reach the maximum with a delay after the removal of the occlusion, whereas in the range of the respiratory rhythm, no delay was observed. The hyperemic response to short-term ischemia is assumed to develop under the predominant influence of the arterial-arteriolar component, whereas the dynamics of amplitude oscillations in the range of the respiratory rhythm is a result of the devastation of the venular component after removal of occlusion. In response to short-term ischemia, the maximum oscillation amplitudes of myogenic, neurogenic, and endothelial rhythms decreased with age, which demonstrates the restriction of the regulatory control of the peripheral blood flow by the corresponding systems.     

Cardiac and respiratory oscillations of the blood flow in microvessels of the human skin

Laser Doppler flowmetry with wavelet analysis, spectrophotometry, computer-aided capillaroscopy, and thermometry were used to study cardiac and respiratory oscillations of the blood flow in the skin microvessels of 30 subjects. The amplitudes of the cardiac and respiratory rhythms (A_c and A_r, respectively) were found to be determined predominantly by the distribution of perfusion and pressure in larger vessels (arterioles and venules). The cardiorespiratory coupling is a regulatory factor in the microcirculatory system; at rest, the value of A_c/A_r reflects the capillary arteriovenous ratio. In the structure of the microcirculation index (MI) and A_c, the velocity-to-volume ratio depends on the perfusion of the corresponding skin region: at rest, the volume-related component is expressed only in the skin with arteriolovenular anastomoses, whereas, in the skin without these anastomoses, MI and A_c are predominantly correlated with the dynamic velocity-related component. A_c is inversely dependent on both stationary and oscillatory components of the microvascular tone. The nature of the respiratory wave depends not only on the respiratory modulation of the venous outflow, but also on the perfusion pressure in the microvessels and venular hematocrit. The correlation of A_r with the total blood flow in the skin microvessels and the individual contributions of velocity-and volume-related components to A_r were significant only in situations where the blood flow was above a certain threshold, below which the respiratory waves can penetrate into the microvessels but their correlation with the total perfusion is nonsignificant.     

Synchronized Renal Blood Flow Dynamics Mapped with Wavelet Analysis of Laser Speckle Flowmetry Data

Full-field laser speckle microscopy provides real-time imaging of superficial blood flow rate. Here we apply continuous wavelet transform to time series of speckle-estimated blood flow from each pixel of the images to map synchronous patterns in instantaneous frequency and phase on the surface of rat kidneys. The regulatory mechanism in the renal microcirculation generates oscillations in arterial blood flow at several characteristic frequencies. Our approach to laser speckle image processing allows detection of frequency and phase entrainments, visualization of their patterns, and estimation of the extent of synchronization in renal cortex dynamics.     

Evaluation of the parameters of total,nutritive, and shunt blood flows in the skin microvasculature using laser Doppler flowmetry

Examination of 28 healthy subjects and 66 patients was performed using laser Doppler flowmetry (LDF) of the skin of fingers in the red and infrared ranges and wavelet analysis of microvascular blood flow oscillations. Formulas were suggested for the total (TF), nutritive (NF), and shunt (SF) local blood flows. TF = MI × A_c × A_n /(P_m × ), where MI is the microcirculation index in perfusion units (PU), A_n and A_c are the averaged maximum amplitudes of the neurogenic and cardiac rhythms (in PU), P_m is the mean arterial pressure (in mm Hg), and is the mean square deviation of the amplitude of blood flow oscillations (in PU). NF = TF/SP, where SP is the shunting parameter. SP = A_n/A_m, where A_m is the averaged maximum amplitude of the myogenic rhythm (in PU). SF = TF - NF. Significant positive relationships between the skin oxygenation and NF (red), temperature and TF (red), and blood flow measured by hydrogen clearance and TF (infrared) were revealed by comparison of the LDF parameters with polarographic and thermographic data. The advantages of the LDF parameters compared with the MI were shown, especially in skin denervation syndromes. The TF decreased in the case of complete anatomic rupture of the median nerve and increased in reflex sympathetic dystrophy, with both cases being accompanied by a deficit of the NF (red).Translated from Fiziologiya Cheloveka, Vol. 31, No. 1, 2005, pp. 114–119.Original Russian Text Copyright © 2005 by Krupatkin.     

Study of endothelium-dependent blood oscillations in the human skin microcirculatory bed

Cutaneous microcirculation parameters were studied with laser Doppler flowmetry in healthy volunteers. To investigate endothelial-dependent peripheral blood flow oscillations the iontophoresis of 1% acetylcholine solution was carried out. To estimate the contribution of rhythmical components in blood flow signal the continuous wavelet-transform spectral analysis was used. To reveal correlation between microcirculation parameters under study the correlation analysis was used. The microcirculation index was shown to be the factor producing cross-correlation dependences. The only positive significant correlation between the blood flow oscillation amplitude in the range of endothelial activity normalized to mean microcirculation index at rest and maximal microcirculation index during the iontophoresis of acetylcholine was revealed.     

Age-dependent characteristics of the skin peripheral blood flow oscillations by nonlinear dynamics methods in humans

Study of peripheral microhaemodynamics was carried out with laser Doppler flowmetry in healthy volunteers of different age groups. The ageing changes in the state of the skin peripheral blood flow, in the functioning of separate links and regulatory systems ofmicrovascular bed have been estimated in terms of relative entropy and fractal dimension values. The revealed significant age-dependent decrease of relative entropy values in the respiratory rhythm ranges, the neurogenic and myogenic activities yielded some evidence concerning the reduction of the microcirculation system chaotic changes within these frequency ranges during the ageing. The significant increase of fractal dimension values in the ranges of cardio-rhythm and the endothelial activity in the oldest group with the mean age of 77 years indicated that the structural complexity of the oscillations in these frequency ranges increased during ageing.     

The Effect of Local Application of Natural Hirudin on Random Pattern Skin Flap Microcirculation in a Porcine Model

The aim of this study was to investigate the effect of local administration of hirudin in improving random pattern skin flap microcirculation in a porcine model. Five Chinese minipigs were used and six dorsal random pattern skin flaps were elevated in each animal (4 × 14 cm). All flaps (n = 30) were assigned to experimental (n = 10), control (n = 10), and sham (n = 10) groups. Flap edema measurement showed that edema in experimental flaps was more severe (P < 0.05) than either control or sham flaps. Local blood flow detection showed an increased image signal of blood flow in experimental flaps instead of an obvious avascular area in control and sham flaps. The survival area was significantly greater in experimental group (67.6 ± 2.1 %) as compared to control (45.2 ± 1.4 %) or sham (48.3 ± 1.1 %) group (P < 0.05). Our data showed that local administration of hirudin can significantly improve random pattern skin flap microcirculation in over dimensioned random pattern skin flaps in a porcine model.     

The problem of information value in microvascular networks

A novel methodology of quantitative estimation of the information value in microvascular networks is proposed. The methodology has been developed on the basis of the results of wavelet analysis of skin blood flow oscillations measured by means of laser Doppler flowmetry (LDF) in 30 healthy subjects and 56 patients with hand diseases or consequences of hand injuries. The method is based on the calculation of the relative indices of information preservation, dominance of the preserved information, and information effectiveness. The deviation from the multistable information regimen is the largest in the case of resonance oscillations: the total information quantity is significantly decreased; however, the preservation of dominant information and its effectiveness are improved. The preservation of trophic myogenic information predominates upon reduction of sympathetic influences. An increase in the number of information channels increases only the information quantity, whereas the degree of its preservation varies. Sensory peptidergic nerve fibers are activated in response to local heating of the dorsal forearm skin to 34°C. This information is the most effective at the beginning of the heating, when the blood flow increases to a plateau. The blood flow oscillations represented in the wavelet spectrum of microcirculatory oscillations serve as operators based on effective information. These oscillations not only play the hemodynamic role, but also carry information in microvascular networks.     

Dynamic oscillatory circuit of regulation of capillary hemodynamics

We used laser Doppler flowmetry with wavelet analysis of blood flow oscillations, computer capillaroscopy, and thermometry of the nail bed in 30 subjects to show an important role of the oscillatory circuit in the regulation of capillary hemodynamics, number of functioning capillaries, and linear and volumetric velocity of blood flow. The number of functioning capillaries is regulated by oscillations of myogenic and sensory peptidergic origin. The appearance of sensory oscillations, especially high-amplitude oscillations, is an adaptive neurotrophic mechanism that significantly increases the number of functioning capillaries and intensity of blood flow from arterioles to capillaries. The linear velocity of blood flow depends on both the tone of microvessels and changes in the dynamic component of blood pressure. Under conditions of skin hypoperfusion, the mean linear velocity of capillary blood flow may be inversely related to the extracapillary perfusion, including the amplitude of heart rate (A _h) and oscillations of the tone of precapillary sphincters, whereas under conditions of vasodilation and increased skin perfusion, it may be inversely related to the amplitude of arteriolar oscillations of endothelial or neurogenic sympathetic origin (A _maxe + n) and the shunting index. The A _h affects the linear velocity of blood flow in the arterial part of capillaries, whereas the A _maxe + n influences the same factor in the venous part. The contribution of oscillations to the regulation of the linear velocity varies depending on the perfusion and skin temperature. The resultant tone of distributing microvessels is determined by the competition between the stationary and oscillatory components. In addition to changes in the amplitude, the frequency of vasomotions may also be important. The regulatory importance of the oscillatory circuit is increased with a decrease in the skin blood flow.     

Estimation of the microcirculation state in cerebrovascular disorders using laser doppler flowmetry data and hemorheological parameters

The microcirculation state was assessed in the group of patients with ischemic stroke (n = 30) and the control group of healthy individuals (n = 27) using laser Doppler flowmetry and the wavelet analysis of the amplitude-frequency range of microvascular blood flow oscillations combined with absorption spectroscopy. The hemorheological parameters (blood and plasma viscosity, the degree of red blood cell aggregability and deformability) were assessed in both groups, as were their correlations with the microcirculation parameters. Decreased tissue perfusion (by 25%) and specific oxygen consumption (by 21%) were revealed in a cerebrovascular accident. Changes in the tone-forming regulatory mechanisms of microcirculation of vasodilating nature (decreased microvascular tone, activation of the secretory function of endothelium) may be regarded as a compensatory reaction aimed at maintaining the blood supply of organs and tissues in stroke. The blood viscosity increase in patients due to the plasma viscosity increase and increased red blood cell aggregability and their decreased deformability cause the blood flow to slow down and the wall shear stress to increase, which activates the endothelial secretory function and vasodilation of microvessels. Correlation between the rheological parameters and the passive (respiratory and cardiac) rhythm amplitudes was observed in the control group. In patients, the hemorheological parameters were correlated with the characteristics of the active factors of microvascular blood flow modulation (endothelial, neurogenic, and myogenic), which confirms the role of changed blood properties and regulatory tone-forming mechanisms in the maintenance of tissue perfusion in cerbrovascular accidents.     

Oscillatory structures of blood flow reflect the dynamics of information processes in microcirculatory networks

Laser Doppler flowmetry with wavelet analysis of oscillations of the blood flow in the glabrous skin of the second and fifth fingertips of 30 healthy individuals and 57 patients before and after median and ulnar nerve sutures (n = 29) and after hand sympathectomy (n = 28). Information processes in microvascular networks include both the stationary and oscillatory components. This study is the first to apply wavelet analysis of the blood flow oscillatory organization to studying the dynamics of information processes in microcirculatory networks. A methodological approach was proposed to estimate the total quantity of information, the value and semantic features of different information channels and the information regime (multichannel or resonance) in microcirculatory networks. The deficit of both general information and its content (particularly, of external information), a decrease in the accessibility to the information and the system of self-organization were typical during the denervation syndrome. The semantic information signs changes mainly after sympathectomy. The dynamics of the information process reflects the functional significance of microcirculation in the course of nerve regeneration and skin reinnervation. The increment in information quantity with trophic content occurred at the preimpulse stage of nerve regeneration; it corresponds to the quantitative development of skin microvascular networks for trophic support of reinnervation. The semantic information content was predominantly modulated at the impulse stage due to the increase in homeostatic control intensity. Information peculiarities in the transitional period (from the preimpulse to impulse stage) included a decrease in sporadic processes, an increase in determinism in the system control, the predomination of the trophic content assimilation with the increment in the myogenic activity proper, and the possibility of both multichannel and resonance regimes. The general biological law of the antientropic importance of information for decreasing stochastic processes and the system control support has been confirmed.     

Involvement of the sympatho-vagal balance in the formation of respiration-dependent oscillations in the human cardiovascular system

The effect of deep breathing controlled in both rate and amplitude on the heart rate variability (HRV) and respiration-dependent blood flow oscillations was studied in the forearm and finger-pad skin of healthy 18- to 25-year-old volunteers. In order to reveal the effects of the divisions of the autonomic nervous system on the amplitudes of respiratory sinus arrhythmia (RSA) and skin blood flow oscillations, we studied the indices of the cardiovascular system in two groups of subjects with respectively lower and higher values of the sympatho-vagal balance. This index was calculated as a ratio of low frequency and high frequency HRV spectral power (LF/HF) under the conditions of spontaneous breathing. It was found that, in subjects with a predominant parasympathetic tone, the amplitudes of RSA and the rate of blood flow in the finger-pad skin were higher compared to subjects with a predominant sympathetic tone during respiration with the frequency lower than 4 cycle/min. In the forearm skin, where sympathetic innervation is weaker compared to the finger-pad skin, there were no significant differences in respiration-dependent oscillations of the rate of blood flow in two groups of subjects.     

Relation between microcirculation parameters and Pc3 geomagnetic pulsations

An individual analysis of long-term monitoring of microcirculation parameters of nine healthy volunteers showed that an increase in the geomagnetic activity led to an increase in tissue perfusion, variability of blood flow and growth of the amplitude of neurogenic and myogenic oscillations in four volunteers. It was found that the degree of microcirculation sensitivity to the level of geomagnetic activity varies with time and is proportional to its average level in the period of measurement. A comparison of frequency ranges of oscillations of blood flow and variations of the geomagnetic activity shows that neurogenic and myogenic oscillations showing the highest sensitivity to the geomagnetic activity have the same frequency as geomagnetic Pc3 pulsations. The pulsations of this frequency range are excited mainly during geomagnetic disturbances, which may explain the correlation between the microcirculation parameters and the K _p-index. The relation of the amplitude-frequency characteristics of Pc3-pulsations can explain the results obtained using Lednev’s model which treats the spins of hydrogen nuclei as a primary target of action for extremely weak alternating magnetic fields.     

Effect of transcutaneous electrical spinal cord stimulation on the blood flow in the skin of lower limbs

Changes in the blood flow in the skin of the plantar surface of the hallux were investigated by laser Doppler flowmetry in eight healthy subjects during transcutaneous electrical spinal cord stimulation (tESCS) with the pulse parameters used to activate locomotion. Continuous tESCS in the area of C5–C6 vertebrae did not cause significant changes in the blood flow, while electrical stimulation at T ₁₂–T ₁ and L ₁–L ₂ levels resulted in an increase in skin perfusion by 22–27%. Wavelet analysis of microcirculatory fluctuations showed that tESCS induced flaxomotions in the range of sensory peptidergic fibers and enhanced the amplitude of fluctuations of microcirculation in the endothelium-dependent range. These results suggest that tESCS stimulates microcirculation in the skin mainly due to antidromic stimulation of sensory peptidergic nerve fibers, which promotes activity of microvascular endothelium, vasodilator secretion, a decrease in vascular resistance, and an increase in microcirculation.     

Involvement of sympathetic nerve activity in skin blood flow oscillations in humans

We have used the wavelet transform to evaluate the time-frequency content of laser-Doppler flowmetry (LDF) signals measured simultaneously on the surfaces of free microvascular flaps deprived of sympathetic nerve activity (SNA), and on adjacent intact skin, in humans. It was thereby possible to determine the frequency interval within which SNA manifests itself in peripheral blood flow oscillations. The frequency interval from 0.0095 to 2 Hz was examined and was divided into five subintervals: I, approximately 0.01 Hz; II, approximately 0.04 Hz; III, approximately 0.1 Hz; IV, approximately 0.3 Hz; and V, approximately 1 Hz. The average value of the LDF signal in the time domain as well as the mean amplitude and total power in the interval from 0.0095 to 2 Hz and amplitude and power within each of the five subintervals were significantly lower for signals measured on the free flap (P < 0.002). The normalized spectral amplitude and power in the free flap were significantly lower in only two intervals: I, from 0.0095 to 0.021 Hz; and II, from 0.021 to 0.052 Hz (P < 0.05); thus indicating that SNA is manifested in at least one of these frequency intervals. Because interval I has recently been shown to be the result of vascular endothelial activity, we conclude that we have identified SNA as influencing blood flow oscillations in normal tissues with repetition times of 20-50 s or frequencies of 0.02-0.05 Hz.