Nitric oxide and neurally mediated regulation of skin blood flow during local heating.

The mechanisms underlying the skin blood flow (SkBF) response to local heating are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different interventions, including blockade of the axon reflex (EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (> or =10 mM N(G)-nitro-L-arginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a percentage of maximal SkBF (SkBF(max); 50 mM sodium nitroprusside). At the initiation of local heating, SkBF rose to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial peak from 75+3 to 32 +/- 2% SkBF(max) (P < 0.01 vs. control) but did not affect the plateau. NOS inhibition before and throughout local heating reduced the initial peak from 75 +/- 3 to 56 +/- 3% SkBF(max) (P < 0.01) and the plateau from 87 +/- 4 to 40 +/- 5%. NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone. Antebrachial nerve block did not affect the local heating SkBF response. The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO.     

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 effect of local heating on blood flow in the finger and the forearm skin

Blood flow of the finger and the forearm were measured in five male subjects by venous occlusion plethysmography using mercury-in-Silastic strain gauges in either a cool-dry (COOL: 25 degrees C, 40% relative humidity), a hot-dry (WARM: 35 degrees C, 40% relative humidity), or a hot-wet (HOT: 35 degrees C, 80% relative humidity) environment. One hand or forearm was immersed in a water bath, the temperature (Tw) of which was raised every 10 min by steps of 2 degrees C until it reached 41 degrees or 43 degrees C. While the other hand or forearm was kept immersed in a water bath (Tw, 35 degrees C), blood flow in the heated side (BFw) was compared with the corresponding blood flow in the control side (BFc). Under WARM or HOT conditions, finger BFw was significantly lower than finger BFc at a Tw of 39-41 degrees C in the majority of subjects. When Tw was raised to 43 degrees C, however, finger BFw became higher than BFc in nearly half of the subjects. In the COOL state, finger BFw did not decrease but increased steadily when Tw increased from 37 degrees to 43 degrees C. In the forearm, BFw increased steadily with increasing Tw even in WARM-HOT environments. No such heat-induced vasoconstriction was observed in the forearm. From these results we conclude that in hyperthermic subjects, the rise in local temperature to above core temperature produces vasoconstriction in the fingers, an area where no thermal sweating takes place.     

Increased flow of testicular blood plasma during local heating of the testes of rams.

After removal of the scrotal skin, one testis of each of 12 adult anaesthetized rams was kept at 33 degrees C for 60 min, then heated either to 36 degrees C for 60 min and then to 39 degrees C for 60 min, or to 36 degrees C for 120 min and then returned to 33 degrees C for 100 min, while the other testis was maintained at 33 degrees C. Flow of testicular blood plasma was measured every 10 min using the technique of dilution of sodium p-aminohippurate. When the temperature of the testis was raised to 36 degrees C, flow of blood plasma gradually increased and reached a higher than normal rate at the end of the first hour, without any further increase during the second hour. The increase in mean flow rate was 25.8 +/- 3.4% (mean +/- SEM) during the second hour at 36 degrees C, and 77.1 +/- 12.8% during the hour at 39 degrees C, compared with the respective values at 33 degrees C. No significant changes were seen in testicular lymph flow determined by collection for 10 min in four rams at 36 degrees C (60 min) and then at 39 degrees C (60 min). These results are different from those from earlier studies in which total blood flow was unchanged when the scrotum and testes were heated. The difference could be related either to lack of heating of the scrotum or to the lower temperatures used in the present study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigating high-amplitude oscillations in rat tail skin blood flow during core heating and cooling

In a separate paper, we describe high-amplitude oscillations in human skin blood flow (Q˙_sk). Using an open-loop model in rats, we independently modulated and clamped hypothalamic and skin temperatures. Central heating reliably induced these high-amplitude oscillations in tail Q˙_sk, which occurred at 0.41±0.03 Hz spanning 758.1±25.7 ms, and were comprised of high-amplitude peaks (496.8±87.6 AU) arising from a stable baseline (114.1±27.6 AU). Central cooling significantly reduced Q˙_sk, but not the amplitude, the frequency, width or baseline of the oscillations. These observations indicate that such high-amplitude oscillations are not primarily mediated via central thermal state. Instead, we believe these oscillations to be turned on by an elevated skin temperature.     

Finger dexterity, skin temperature, and blood flow during auxiliary heating in the cold.

The primary purpose of the present study was to compare the effectiveness of two forms of hand heating and to discuss specific trends that relate finger dexterity performance to variables such as finger skin temperature (T(fing)), finger blood flow (Q(fing)), forearm skin temperature (T(fsk)), forearm muscle temperature (Tfmus), mean weighted body skin temperature (Tsk), and change in body heat content (DeltaH(b)). These variables along with rate of body heat storage, toe skin temperature, and change in rectal temperature were measured during direct and indirect hand heating. Direct hand heating involved the use of electrically heated gloves to keep the fingers warm (heated gloves condition), whereas indirect hand heating involved warming the fingers indirectly by actively heating the torso with an electrically heated vest (heated vest condition). Seven men (age 35.6 +/- 5.6 yr) were subjected to each method of hand heating while they sat in a chair for 3 h during exposure to -25 degrees C air. Q(fing) was significantly (P < 0.05) higher during the heated vest condition compared with the heated gloves condition (234 +/- 28 and 33 +/- 4 perfusion units, respectively), despite a similar T(fing) (which ranged between 28 and 35 degrees C during the 3-h exposure). Despite the difference in Q(fing), there was no significant difference in finger dexterity performance. Therefore, finger dexterity can be maintained with direct hand heating despite a low Q(fing). DeltaH(b), Tsk, and T(fmus) reached a low of -472 +/- 18 kJ, 28.5 +/- 0.3 degrees C, and 29.8 +/- 0.5 degrees C, respectively, during the heated gloves condition, but the values were not low enough to affect finger dexterity.     

Determination of local brain blood flow by means of switched heating]

It is demonstrated by model experiments that the determination of stationary and instationary data (amplitude and shape of the heating signal) allows the two components of local brain perfusion (flow rate and volume flux) to be measured separately. Since perfusion and temperature are measured at the same site, the convection data are free of variations of the local brain temperature. The dependence of the amplitude of the heating signal on the flow rate is described by the equation Ao = a - e-bv + c, with the parameters a, b, c being represented as a function of the convection-free space around the sensing probe. It is shown by animal-experimental data that the magnitude of the convection-free space around the sensing probe is variable. A tentative algorithm is proposed for practical application of the method.     

Regional cerebral blood flow changes during hypothermia

1. 1. When brain temperature was decreased from 38 to 22 °C using selective hypothermia, tissue blood flow decreased significantly in cerebral cortex, cerebellum, and thalamus, but did not significantly change in hypothalamic or brain stem tissue.

2. 2. A further decrease in brain temperature to 8 °C produced an increase in blood flow in all tissues except cerebral cortex compared to tissue blood flow measured at 22 °C. Compared to normothermic values, blood flow remained significantly decreased at 8 °C in cerebral and cerebellar cortex and was increased in brain stem.

3. 3. After rewarming, tissue blood flow returned to original baseline values in all tissues except cerebral cortex where blood flow was slightly but significantly decreased and brain stem, where blood flow was increased.

4. 4. These results indicate that the cerebrovascular effects of selective brain cooling are regionally specific. These changes appear to be due to both direct and indirect effects of cerebral hypothermia since brain tissue blood flow changes are apparent, compared to control values, after rewarming of the brain.

     

Local heating of human skin by millimeter waves: effect of blood flow

We investigated the influence of blood perfusion on local heating of the forearm and middle finger skin following 42.25 GHz exposure with an open ended waveguide (WG) and with a YAV mm wave therapeutic device. Both sources had bell-shaped distributions of the incident power density (IPD) with peak intensities of 208 and 55 mW/cm(2), respectively. Blood perfusion was changed in two ways: by blood flow occlusion and by externally applied vasodilator (nonivamide/nicoboxil) cream to the skin. For thermal modeling, we used the bioheat transfer equation (BHTE) and the hybrid bioheat equation (HBHE) which combines the BHTE and the scalar effective thermal conductivity equation (ETCE). Under normal conditions with the 208 mW/cm(2) exposure, the cutaneous temperature elevation (DeltaT) in the finger (2.5 +/- 0.3 degrees C) having higher blood flow was notably smaller than the cutaneous DeltaT in the forearm (4.7 +/- 0.4 degrees C). However, heating of the forearm and finger skin with blood flow occluded was the same, indicating that the thermal conductivity of tissue in the absence of blood flow at both locations was also the same. The BHTE accurately predicted local hyperthermia in the forearm only at low blood flow. The HBHE made accurate predictions at both low and high perfusion rates. The relationship between blood flow and the effective thermal conductivity (k(eff)) was found to be linear. The heat dissipating effect of higher perfusion was mostly due to an apparent increase in k(eff). It was shown that mm wave exposure could result in steady state heating of tissue layers located much deeper than the penetration depth (0.56 mm). The surface DeltaT and heat penetration into tissue increased with enlarging the irradiating beam area and with increasing exposure duration. Thus, mm waves at sufficient intensities could thermally affect thermo-sensitive structures located in the skin and underlying tissue.     

Effect of local cooling on skin temperature and blood flow of men in Antarctica

Alterations to the finger skin temperature (Tsk) and blood flow (FBF) before and after cold immersion on exposure to an Antarctic environment for 8 weeks were studied in 64 subjects. There was a significant fall in Tsk and increase in finger blood flow after 1 week of Antarctic exposure. The Tsk did not further change even after 8 weeks of stay in Antarctica but a significant increase in FBF was obtained after 8 weeks. The cold immersion test was performed at non-Antarctic and Antarctic conditions by immersing the hand for 2 min in 0–4° C cold water. In the non-Antarctic environment the Tsk and FBF dropped significantly (P < 0.001) indicating a vasoconstriction response. Interestingly after 8 weeks of stay in Antarctic conditions, the skin temperature dropped (P < 0.001) but the cold induced fall in FBF was inhibited. Based on these observations it may be hypothesized that continuous cold exposure in Antarctica results in vasodilatation, which overrides the stronger vasoactive response of acute cold exposure and thus prevents cold injuries.     

Dynamic response characteristics of local muscle blood flow regulatory mechanisms in human forearm exercise.

We sought to understand the nature of control mechanisms involved in the adaptation of exercising muscle hyperemia. Seven subjects performed rhythmic dynamic forearm exercise under two exercise conditions: small step 1 [step increase from rest to 40% peak forearm vascular conductance (FVC), in ml.min(-1).100 mmHg-1] for 5 min followed by small step 2 (further increase to 80% peak FVC for 5 min), and large step (step increase from rest to 80% peak FVC for 5 min). FVC data were fit with a two- (small step 1) and three-component (small step 2, large step) exponential as appropriate. For the rapid phase I response, FVC dynamic response characteristics (time delay, time constant) were not affected by the magnitude of the work intensity increase when the transition began from rest, but were slower in the 40-80% transition. Rest-80% gain was greater than either rest-40% or 40-80% transitions but represented the same proportion of the phase I + phase II gain across all transitions (57 vs. 56 vs. 57%, respectively, P = 0.975). For the slower phase II response, dynamic response characteristics were not affected by the magnitude of the work intensity increase when initiated from rest. The time constant was not altered when the transition began from exercise vs. rest. We conclude that 1) dynamic response characteristics of exercise hyperemia control mechanisms are not affected by the magnitude of work rate increase when forearm exercise is initiated from rest, 2) phase I but not phase II dynamic response characteristics are sensitive to baseline exercise intensity, and 3) the mechanisms contributing to phase I result in the same relative response magnitude, regardless of the size of the step increase in exercise intensity or the baseline from which it is initiated.     

The influence of topical capsaicin on the local thermal control of skin blood flow in humans

To test whether heat-sensitive receptors participate in the cutaneous vascular responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler flowmetry) where the sensation of heat was induced either by local warming (T(Loc); Peltier cooling/heating unit) or by both direct warming and chemical stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical capsaicin (0.075 or 0.025%) was applied to 12 cm(2) of skin 1 h before stepwise local warming of untreated and capsaicin-treated forearm skin. Pretreatment with 0.075% capsaicin cream shifted the SkBF/T(Loc) relationship to lower temperatures by an average of 6 +/- 0.8 degrees C (P < 0.05). In part II, we used a combination of topical capsaicin (0.025%) and local warming to evoke thermal sensation at one site and only local warming to evoke thermal sensation at a separate site. Cutaneous vasomotor responses were compared when the temperatures at these two sites were perceived to be the same. SkBF differed significantly between capsaicin and control sites when compared on the basis of actual temperatures, but that difference became insignificant when compared on the basis of the perceived temperatures. These data suggest heat-sensitive nociceptors are important in the cutaneous vasodilator response to local skin warming.