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.     

The use of information process indices for the prediction of sympathectomy efficiency in complex regional pain syndrome

The key role of information processes for ensuring the optimal sanogenesis in humans was shown by the wavelet-analysis of skin microvascular blood flow oscillations in 64 patients with complex regional pain syndrome after sympathectomy. The early reorganization of information in the trophotropic direction at the level of microvascular tissue systems, and its predominance and preservation along the microvascular networks facilitate optimal adaptive reactions and, as a result, are conducive to maximum treatment efficiency. In these cases, the complete elimination of disease and the achievement of excellent treatment results are possible. The maximum treatment efficiency could not be reached without the above-mentioned informational changes. On the contrary, the predominance and preservation of ergotropic information in the early periods after surgery were unfavorable for the prediction of the clinical outcome of sympathectomy. Tissue sympathectomy is not required for the formation of the trophotropic type of information exchange in microvascular networks; it is enough to achieve a certain threshold of a sympathetic activity decrease. The results obtained may be useful for investigating the physiological mechanisms of informational treatment technologies (homeopathy etc.).     

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.     

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.     

The problem of adaptation and oscillatory processes in the microvascular bed

Healthy people (n = 16), patients with autonomic dystonia syndrome (n = 38), and patients with traumatic rupture of the median nerve before and after nerve suture (n = 28) were examined by laser Doppler flowmetry (LDF) with a computer wavelet analysis of blood flow oscillations. Functional states (FSs) of the microcirculatory bed wеre assessed using energetic and information indices of microvascular blood flow oscillations. The variation coefficient and the information regime (multistable or resonance) were used as key characteristics. Oscillatory processes are an integral part of adaptation and the FS formation in the microvascular bed. FSs were classified as adaptive, hyperadaptive, hypoadaptive, and failure of adaptation. Because supporting the optimal function of nutritive microvessels is a leading component of the adaptation process, FSs of nutritive and nonnutritive microvessels may differ. A selective contribution of the autonomic sympathetic regulatory channel was related to maintaining considerable hyperadaptation in the microvascular bed with overstrain or marked overstrain of regulatory systems, as in emotional stress. Hypoadaptive FSs formed when skin blood flow increased, an excess decrease in flow resistance was unnecessary, and especially when regulatory factors were in deficiency, e.g., in neurodystrophic syndrome.     

The use of information processes indices for prediction of sympathectomy efficiency in complex regional pain syndrome

Key significance of information processes for ensuring optimal sanogenesis was shown by wavelet-analysis of skin microvascular blood flow oscillations at 64 patients with complex regional pain syndrome after sympathectomy Early reorganization of information in trophotropic direction at the level of microvascular tissue systems, its predomination and conservation all along the microvascular networks facilitate optimal realization of adaptive reactions and, as a result, are conductive to maximum treatment efficiency. In these cases complete elimination of disease and achievement of excellent treatment results were possible. Maximum treatment efficiency could not be reached without the above-mentioned information changing. On the contrary predomination and conservation of ergotropic information at the early periods after surgery were unfavourable to prediction of clinical results of sympathectomy Tissue desympathisation is not required to formation of information trophotropic purposefulness in microvascular networks; it is enough to achieve certain threshold of sympathetic activity decrease. The results of this work may be useful for investigation of physiological mechanisms of information treatment technologies (homeopathy etc.).     

Influence of sensory peptidergic innervation on human skin blood flow oscillations in the range 0.047–0.069 Hz

Thirty-six healthy subjects and 65 patients with neurogenic inflammation (complex regional pain syndrome of the hand) or denervation syndromes (after median and ulnar nerve injuries or transplantation of denervated vascularized musculocutaneous autografts), as well as after thoracoscopic sympathectomy, underwent laser Doppler flowmetry with spectral wavelet analysis of the blood flow oscillations in cutaneous microvessels and thermography. It was shown that, along with maintenance of the blood flow oscillations of endothelial genesis, peptidergic sensory nerve fibers (SPFs) are involved in activating independent, including high-amplitude, oscillations in the myogenic range 0.047–0.069 Hz (an average of three to four oscillations per minute). The above-mentioned oscillations were recorded against the background of neurogenic inflammation and nociceptive activation of C afferents after nerve injuries, as well as in the course of functional tests in healthy subjects (the forearm skin electrostimulation test, capsaicin application). Sympathectomy and hyposympathicotonia contributed to their manifestation; they were not detected under the conditions of severe sensory-trophic skin denervation. The appearance of high-amplitude blood flow oscillations in human skin microvessels at a frequency of 0.047–0.069 Hz may serve as an objective criterion of SPF activation.     

Oscillatory processes in lymph microcirculation in the human skin

This study was the first to use laser Doppler flowmetry followed by wavelet analysis in order to estimate oscillations in lymph microcirculation in 30 subjects with (n = 13) or without (n = 17) edema of the distal part of the upper limb. Lymph flow in the human skin exhibited clear dominance of pacemaker phase oscillations in the frequency ranges of 0.021–0.042 and 0.016–0.035 Hz in the skin of the palm surface of the finger nail bone and in the skin of the forearm, respectively. Edema was associated with an increase in the peak frequencies and normalized maximum amplitudes (Al/Ml, where Al is the mean value of the maximum amplitude of phase oscillations, and Ml is the value of the averaged lymph flow expressed in perfusion units). Low-amplitude oscillations were recorded rarer in the myogenic, endothelial, and respiratory ranges. We did not find any cardiac pulse rhythm in the wavelet spectrum of the lymph flow. We did not find any interaction between the Al/Ml value and the skin temperature. In the group of subjects without edema, under physiological conditions only, we found a negative correlation between the Al/Ml value and the amplitudes of myogenous proper blood flow oscillations, which reflected the number of functional capillaries and activity of oxidative metabolism in the tissue. In the group with edema, we did not find any correlations between the indices of lymph flow and blood flow. The values of normalized amplitude and frequency of phase oscillations may be used as efficient diagnostic tools in the studies on lymph microcirculation.     

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.     

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.     

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.     

Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for metabolic flow regulation in heterogeneous microvascular networks

The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.     

Structural response of microcirculatory networks to changes in demand: information transfer by shear stress

Matching blood flow to metabolic demand in terminal vascular beds involves coordinated changes in diameters of vessels along flow pathways, requiring upstream and downstream transfer of information on local conditions. Here, the role of information transfer mechanisms in structural adaptation of microvascular networks after a small change in capillary oxygen demand was studied using a theoretical model. The model includes diameter adaptation and information transfer via vascular reactions to wall shear stress, transmural pressure, and oxygen levels. Information transfer is additionally effected by conduction along vessel walls and by convection of metabolites. The model permits selective blocking of information transfer mechanisms. Six networks, based on in vivo data, were considered. With information transfer, increases in network conductance and capillary oxygen supply were amplified by factors of 4.9 +/- 0.2 and 9.4 +/- 1.1 (means +/- SE), relative to increases when information transfer was blocked. Information transfer by flow coupling alone, in which increased shear stress triggers vascular enlargement, gave amplifications of 4.0 +/- 0.3 and 4.9 +/- 0.5. Other information transfer mechanisms acting alone gave amplifications below 1.6. Thus shear-stress-mediated flow coupling is the main mechanism for the structural adjustment of feeding and draining vessel diameters to small changes in capillary oxygen demand.     

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.     

Adaptive wavelet analysis of oscillations in the human peripheral blood flow

The main principles are outlined for spectral timing analysis of the peripheral blood flow oscillations obtained by laser Doppler flowmetry. The oscillations can be studied in a wide frequency range both in stationary and nonstationary conditions during functional tests. The potential of the method has been demonstrated in experiments with the reaction of the microvascular bed to transcutaneous iontophoretic introduction of acetylcholine chloride. The major advantage of the method over conventional wavelet analysis is a significant increase in the “effective” length of the signal analyzed, which allows correct analysis of low-frequency components in much shorter LDF recordings than those commonly used.     

Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g?1·min?1 (P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g?1·min?1 (P < 0.01). While whole body heat stress increased intestinal temperature by ～1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g?1·min?1; heat stress: 1.7 ± 0.3 ml·100 g?1·min?1; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g?1·min?1) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress.     

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.     

Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress.

Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat (n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (approximately 41 degrees C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 +/- 0.89 optical density (OD), after heating = 18.21 +/- 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9 degrees C) also caused large increases in the tissue oxygenation signal (before heating = -0.31 +/- 1.47 OD, after heating = 12.48 +/- 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 +/- 0.02) and whole body heating (mean r = 0.89 +/- 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).     

Real-time technique for conversion of skin temperature into skin blood flow: human skin as a low-pass filter for thermal waves

Monitoring of skin blood flow oscillations related with mechanical activity of vessels is a very useful modality during diagnosis of peripheral hemodynamic disorders. In this study, we developed a new model and technique for real-time conversion of skin temperature into skin blood flow oscillations, and vice versa. The technique is based on the analogy between the thermal properties of the human skin and electrical properties of the special low-pass filter. Analytical and approximated impulse response functions for the low- and high-pass filters are presented. The general algorithm for the reversible conversion of temperature into blood flow is described. The proposed technique was verified using simulated or experimental data of cold stress, deep inspiratory gasp, and post-occlusive reactive hyperaemia tests. The implementation of the described technique will enable to turn a temperature sensor into a blood flow sensor.     

Effect of hand heating by a warm air box on O2 consumption of the contralateral arm.

Arterialization of venous blood is often used in studying forearm metabolism. Astrup et al. [Am. J. Physiol. 255 (Endocrinol. Metab. 18): E572-E578, 1988] showed that heating of the hand by a warming blanket caused a redistribution of blood flow in the contralateral arm and thus introduced errors in forearm skeletal muscle flux calculations. The present study was undertaken to investigate how hand heating by a warm air box (60 degrees C) would affect metabolism and blood flow in the contralateral arm before and during 3 h after a glucose load. Eleven healthy volunteers (5 males, 6 females) underwent an oral glucose tolerance test (70 g) on two different occasions, one test with and one without heating of the contralateral hand, in random order. Heating the hand for 30 min before glucose intake did not affect skin temperature, rectal temperature, deep venous oxygen saturation, forearm blood flow, or oxygen consumption of forearm skeletal muscle. Although, after the glucose load, heating significantly increased forearm blood flow (P less than 0.05), the integrated response after glucose was not significantly different between control and heating experiments [67 +/- 43 and 117 +/- 41 (SE) ml/100 ml tissue]. With both conditions, there was an increase in skin temperature (P less than 0.001, integrated response control: 369 +/- 79 and heating: 416 +/- 203 degrees C) and oxygen consumption of forearm muscle (control: 290 +/- 73, P less than 0.05 and heating: 390 +/- 130 mumol/100 ml, P less than 0.05) after glucose intake. These responses did not significantly differ between the conditions.(ABSTRACT TRUNCATED AT 250 WORDS)