Skin Blood Flow Responses to Acetylcholine, Local Heating, and to 60% VO2max exercise with and without Nitric Oxide inhibition, in Boys vs. Girls.

PURPOSE: To determine sex-related differences in the skin blood flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children, and to assess nitric oxide contribution to the SkBF response. METHODS: Forearm SkBF during local heating (44°C), ACh iontophoresis, and exercise (30-min cycling and 60% of maximum oxygen consumption) was assessed, using laser Doppler fluxmetry, in 12 boys and 12 girls (7-13 y old), with and without nitric oxide synthase inhibition, using Nω-nitro-L-arginine methyl ester iontophoresis. RESULTS: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (local heating: 1445% [900%] and 1432% [582%] of baseline, P = .57; ACh: 673% [434%] and 558% [405%] of baseline, respectively, P = .18). Exercise-induced increase in SkBF was greater in boys than girls (528% [290%] and 374% [192%] of baseline, respectively, P = .03). Nω-nitro-L-arginine methyl ester blunted the SkBF response to ACh and during exercise (P < .001), with no difference between sexes. CONCLUSION: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of nitric oxide was not different between boys and girls. It is suggested that the greater SkBF response in boys during exercise was related to greater relative heat production and dissipation needs at this exercise intensity. The response to body size-related workload should be further examined.

Linking the hemodynamic consequences of adverse childhood experiences to an altered HPA axis and acute stress response.

Adverse childhood experiences (ACEs), such as maltreatment and severe household dysfunction, represent a significant threat to public health as ACEs are associated with increased prevalence of several chronic diseases. Biological embedding, believed to be rooted in dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, is the prevailing theory by which chronic diseases become imprinted in individuals following childhood adversity. A shift towards HPA axis hypoactivity occurs in response to ACEs exposure and is proposed to contribute towards altered cortisol secretion, chronic low-grade inflammation, and dysregulated hemodynamic and autonomic function. This shift in HPA axis activity may be a long-term effect of glucocorticoid receptor methylation with downstream effects on hemodynamic and autonomic function. Emerging evidence suggests syncopal tendencies are increased among those with ACEs and coincides with altered neuroimmune function. Similarly, chronic low-grade inflammation may contribute towards arterial baroreceptor desensitization through increased arterial stiffness, negatively impacting autonomic regulation following posture change and increasing rates of syncope in later life, as has been previously highlighted in the literature. Although speculative, baroreceptor desensitization may be secondary to increased arterial stiffness and changes in expression of glucocorticoid receptors and arginine vasopressin, which are chronically altered by ACEs. Several research gaps and opportunities exist in this field and represent prospective areas for future investigation. Here, we synthesize current findings in the areas of acute psychosocial stress reactivity pertaining to HPA axis function, inflammation, and hemodynamic function while suggesting ideas for future research emphasizing systemic interactions and postural stress assessments among those with ACEs. This review aims to identify specific pathways which may contribute towards orthostatic intolerance in populations with history of childhood adversity.

The effects of local forearm heating and cooling on motor unit properties during submaximal contractions.

NEW FINDINGS: What is the central question of this study? How do temperature manipulations affect motor unit (MU) properties during submaximal contractions to the same relative percentage of maximal force? What is the main finding and its importance? MU recruitment patterns are affected by temperature manipulations at the forearm. However, the relationship between MU potential amplitude and recruitment threshold indicates no change to the order or recruitment. Additionally, the MU potential amplitude and firing rate relationship was affected by temperature, suggesting that smaller MUs are more affected by temperature changes than larger MUs. ABSTRACT: Temperature impacts muscle contractile properties, such that experiments with workloads based on thermoneutral values will produce different relative intensities if maximal force changes due to muscle temperature. We investigated how temperature affected motor unit (MU) properties with contractions performed at the same normalized percentage of maximal force. Twenty participants (10 females) completed evoked, maximal, and trapezoidal voluntary contractions during thermoneutral-, hot-, and cold-temperature conditions. Forearm temperature was established using 25 min of neutral (∼32°C), hot (∼44°C) or cold (∼13°C) water circulated through a tube-lined sleeve. Flexor carpi radialis MU properties were assessed with contractions at 30% and 60% MVC relative to each temperature using surface electromyography decomposition. Changes to contractile properties and electromechanical delay from the evoked twitch suggest that muscle contractility was changed from the thermal manipulations (effect size (d) ≥ 0.42, P < 0.05). Maximal force was not different between neutral and hot conditions (d = 0.16, P > 0.05) but decreased in the cold (d ≥ 0.34, P < 0.05). For both contraction intensities, MU potential (MUP) amplitude was larger and duration was longer in the cold compared to neutral and hot conditions (d ≥ 1.24, P < 0.05). Cumulative probability density for the number of MUs recruited revealed differences in MU recruitment patterns among temperature conditions. The relationship between MU recruitment threshold and firing rate or MUP amplitude was not different among temperature conditions (P > 0.05); however, the relationship between MUP amplitude and firing rate was (P < 0.05). Local temperature manipulations appear to affect MU recruitment patterns, which may act as compensatory mechanisms to the changes in muscle viscosity and contractile properties due to local temperature changes.

Noninvasive assessment of increases in microvascular endothelial function following repeated bouts of hyperaemia.

OBJECTIVE: Spectral analyses of laser-Doppler signal can delineate underlying mechanisms in response to pharmacological agents and in cross-sectional studies of healthy and clinical populations. We tested whether spectral analyses can detect acute changes in endothelial function in response to a 6-week intervention of repeated bouts of hyperaemia. METHODS: Eleven males performed forearm occlusion (5 s with 10 s rest) for 30 min, 5 times/week for 6 weeks on one arm; the other was an untreated control. Skin blood flow was measured using laser-Doppler fluxmetry (LDF), and endothelial function was assessed with and without nitric oxide (NO) synthase-inhibition with L-NAME in response to local heating (42 °C and 44 °C) and acetylcholine. A wavelet transform was used for spectral analysis of frequency intervals associated with physiological functions. RESULTS: Basal measures were all unaffected by the hyperaemia intervention (all P > 0.05). In response to local skin heating to 42 °C, the 6 weeks hyperaemia intervention increased LDF, endothelial NO-independent and NO-dependent activity (all P ≤ 0.038). In response to peak local heating (44 °C) endothelial NO-independent and NO-dependent activity increased (both P ≤ 0.01); however, LDF did not (P > 0.2). In response to acetylcholine, LDF, endothelial NO-independent and NO-dependent activity all increased (all P ≤ 0.003) post-intervention. CONCLUSIONS: Spectral analysis appears sufficiently sensitive to measure changes over time in cutaneous endothelial activity that are consistent with standard physiological (local heating) and pharmacological (acetylcholine) interventions of assessing cutaneous endothelial function, and may be useful not only in research but also clinical diagnosis and treatment.

Comparison of laser speckle contrast imaging and laser-Doppler fluxmetry in boys and men.

OBJECTIVE: We compare microvascular reactivity assessed by laser-Doppler fluxmetry (LDF) and laser speckle contrast imaging (LSCI) of boys and men during rest, post-occlusive reactive hyperaemia (PORH), and cycling exercise. METHODS: 19 boys (9 ±â€¯1 y) and 18 men (22 ±â€¯2 y) participated. LDF and LSCI measures were taken of the forearm during rest, PORH, and exercise. RESULTS: For all 3 assessments, the LSCI presented with higher flux values than the LDF for both boys and men (p < 0.001). Bland-Altman analyses indicated that there was a positive linear bias between LSCI and LDF measurements in both boys and men. Regression analyses showed that the responses for the two methods were variable, depending on the particular assessment. For instance, at rest in boys there was no relationship between LDF and LSCI (r2 = 0.002), while in men there was a strong relationship (r2 = 0.86). CONCLUSIONS: LSCI presented with higher values than LDF during rest, PORH, and exercise; the disparity between the two measures was larger as blood flow increased. The assessments were generally consistent, both methods appear to provide usable data for the assessment of microvascular reactivity in both boys and men. There are biases to each method and the data are not interchangeable between LDF and LSCI.

The skin blood flow response to exercise in boys and men and the role of nitric oxide.

PURPOSE: Children thermoregulate effectively during exercise despite sweating rate being consistently lower when compared with adults. The skin blood flow (SkBF) response of children to exercise is inconsistent, when compared with adults. We examined the SkBF response to exercise in children and adults, along with the potential contribution of nitric oxide to the SkBF response. METHODS: Forearm SkBF during cycling (30 min at 60% [Formula: see text]O2max) was investigated in 12 boys (10 ± 1 years) and 12 men (22 ± 2 years) using laser-Doppler flowmetry and Nω-nitro-L-arginine methyl ester (L-NAME) iontophoresis to inhibit nitric oxide synthase. RESULTS: The exercise-induced SkBF increase was similar in boys and men (mean ± SD, 540 ± 127 vs. 536 ± 103% baseline, respectively, p = 0.43, d = 0.01 [- 0.8 to 0.8]). However, the total hyperaemic response to exercise (area-under-the-curve, AUC) indicated that boys had a greater vasodilatory response (cutaneous vascular resistance, CVC) (p < 0.01, d = 0.6 [- 1.2 to 2.8] than the men (134,215 ± 29,207 vs. 107,257 ± 20,320 CVC·s-1). L-NAME blunted the SkBF response more in boys than in men (group-by-treatment interaction, p < 0.001) and resulted in smaller AUC in boys (56,411 ± 23,033 CVC·s-1; p < 0.001, d = 1.4 [- 0.4 to 3.2] compared with men (80,556 ± 28,443 CVC·s-1; p = 0.08, d = 0.8 [0.0-1.6]). Boys had a shorter delay from the onset of exercise to onset of SkBF response compared with men (205 ± 48 and 309 ± 71 s, respectively; p < 0.01, d = 1.7 [0.9-2.8]). L-NAME increased the delay in boys and men (to 268 ± 90 and 376 ± 116 s, respectively; p = 0.01, d = 1.0 [0.4-2.1]) but this delay was not significantly different between the groups (p = 0.85). CONCLUSIONS: These findings suggest that boys experience greater vasodilation and faster increases in SkBF during exercise compared with men. The contribution of nitric oxide to the SkBF response to exercise appears to be greater in boys than in men.

Correction to: The skin blood flow response to exercise in boys and men and the role of nitric oxide.

One of the co-authors, Raffy Dotan, wishes to remove his name from the original version of this article. The corrected author group should be.

The reliability of cutaneous low-frequency oscillations in young healthy males.

OBJECTIVE: Spectral analyses of laser-Doppler flowmetry measures enable a simple and non-invasive method to investigate mechanisms regulating skin blood flow. We assessed within-day and day-to-day variability of cutaneous spectral analyses. METHODS: Eleven young, healthy males were tested twice in three identical sessions, with 19 to 24 days between visits, for a total of six tests. Wavelet data were analyzed at rest, in response to local skin heating to 42 and 44°C, and during 5-minutes PORH. We did this for six frequency bands commonly associated with physiological functions. To assess reliability, we calculated CV and ICC scores. RESULTS: At rest, mean CV for the wavelet data ranged from 21% to 24% and ICC scores ranged from 0.67 to 0.91. During local heating, mean CV scores ranged from 17% to 22% and mean ICC scores ranged from 0.71 to 0.95. For peak PORH, CV ranged from 14% to 23% and the ICC range was 0.88 to 0.97. For the area under the curve of the PORH, CV range was 12% to 21% and ICC range was 0.81 to 0.92. CONCLUSIONS: These analyses indicate good-to-excellent reliability of the wavelet data in healthy young males.

Glabrous and non-glabrous vascular responses to mild hypothermia.

This study examined cutaneous vasoconstriction to whole-body hypothermia, specifically contributions of neural and endothelial vasomotor responses in glabrous and non-glabrous skin. Eleven participants were semi-recumbent at an ambient temperature of 22 °C for 30 min, after which ambient temperature was decreased to 0 °C until rectal temperature (Tre) had decreased by 0.5 °C. Laser-Doppler fluxmetry was measured at the forehead and thigh for measures of glabrous and non-glabrous skin, respectively; wavelet analysis was performed on the laser-Doppler signal to determine endothelial and neural activities. Hypothermia took on average 97 ±â€¯7 min and caused marked decreases at glabrous (42 ±â€¯5%baseline, p < 0.001) and non-glabrous (69 ±â€¯4%baseline, p < 0.001) skin. In glabrous skin, neural activity increased from 11 ±â€¯1% at thermoneutral to 18 ±â€¯1% (p < 0.001). In non-glabrous skin there was an initial decrease (p = 0.001) in neural activity from 13 ±â€¯2% to 9 ±â€¯1% (-0.2 °C decrease in Tre) and then increased (p = 0.002) to 21 ±â€¯2% baseline at -0.5 °C Tre. Endothelial activity decreased in both glabrous (16 ±â€¯3% to 6 ±â€¯1%, p < 0.001) and non-glabrous (15 ±â€¯1% to 7 ±â€¯1%, p = 0.003) skin. Hypothermia elicits large decreases in skin blood flow in both glabrous and non-glabrous skin that are related to increases in neural activity and a reduction of endothelial activity.

The effects of local muscle temperature on force variability.

PURPOSE: Force variability is affected by environmental temperature, but whether the changes are from altered muscle temperature or proprioception are unclear. We tested how forearm muscle warming and cooling affected a force tracking task. METHODS: Twelve males and four females completed evoked, maximal, and isometric wrist flexion contractions (0-30% maximal) during thermoneutral-, warm-, and cold-muscle conditions. Forearm muscle temperature was manipulated using neutral (~ 33 °C), hot (~ 44 °C), or cold (~ 13 °C) water circulated through a tube-lined sleeve. Evoked and voluntary contractions were performed before and after thermal manipulations. RESULTS: Thermal manipulations altered contractile properties as evident in the twitch half-relaxation time, rate of force development, and duration (all P < 0.05), suggesting that muscle temperature was successfully altered. Changes in surface electromyography of the flexor carpi radialis root-mean-square amplitude and mean power frequency between temperature conditions (all P < 0.05) also indicate muscle temperature changes. No changes to root-mean-square error or variance ratio of the force trace were observed with muscle temperature changes (both P > 0.05). Muscle temperature changes did not have a consistent effect on coefficient of variation during each plateau of the staircase contraction. CONCLUSIONS: Our results suggest that the ability to perform a multi-plateaued isometric force task is not affected by changes to forearm muscle temperature. As the thermal manipulation was limited to the forearm, changes to hand temperature would be minimal, thus, proprioception in the wrist and hand was preserved allowing performance to be maintained. Therefore, modest changes to forearm muscle temperature are not likely to affect force variability if proprioception is maintained.

Comparison of different wheelchair seating on thermoregulation and perceptual responses in thermoneutral and hot conditions in children.

We examined the effects of 4 different wheelchair seatings on physiological and perceptual measures in 21 healthy, pre-pubertal children (9 ±â€¯2 years). Participants were able-bodied and did not regularly use a wheelchair. Participants sat for 2 h in Neutral (∼22.5 °C, ∼40%RH) and Hot (∼35 °C, ∼37%RH) conditions. Four seating technologies were: standard incontinent cover and cushion (SEAT1); standard incontinent cover with new cushion (SEAT2) were tested in Neutral and Hot; new non-incontinent cover with new cushion (SEAT3); new incontinent cover and new cushion (SEAT4) were tested in Neutral only. Measurements included skin blood flow (SkBF), sweating rate (SR) and leg skin temperature (TlegB) on the bottom of the leg (i.e. skin-seat interface), heart rate (HR), mean skin temperature, tympanic temperature, thermal comfort, and thermal sensation. During Neutral, SkBF and TlegB were lower (∼50% and ∼1 °C, respectively) and SR higher (∼0.5 mg cm-2·min-1) (p < 0.05) with SEAT3 compared to all other seats. SkBF was ∼30% lower (p < 0.05) for SEAT2 and SEAT4 compared to SEAT1. No other differences were observed between SEATs (all p > 0.05). During Hot, HR and temperatures were higher than in Neutral but there were no differences (p > 0.05) between SEATs. New cover and cushion improved thermoregulatory responses during Neutral but not Hot. An impermeable incontinent cover negated improvements from cushion design. Seat cover appears more important than seat cushion during typical room conditions.

The effect of repeated bouts of hyperaemia on sensory nerve-mediated cutaneous vasodilatation in humans.

PURPOSE: To investigate cutaneous sensory nerve contribution to hyperaemia following chronic shear stress training. METHODS: Eleven males underwent a shear stress intervention (forearm occlusion 5 s, rest 10 s) for 30 min, 5 times·week-1 for 6 weeks on one arm, the other was an untreated control. Skin blood flow was measured using laser-Doppler flowmetry, and sensory nerve function was assessed with and without blockade with EMLA cream in response to 3 levels of local heating (39, 42, and 44 °C) and post-occlusive reactive hyperaemia (PORH). RESULTS: In response to local heating, EMLA treatment significantly delayed the onset of vasodilatation (p < 0.001), time-to-peak (p < 0.001), time to 39 °C (p < 0.02), time to 42 °C (p < 0.006), but not time to 44 °C (p > 0.2). EMLA treatment also increased time-to-peak for PORH (p ≤ 0.01). In the experimental limb after 6 weeks, both onset time and time to peak were shorter in response to local heating at the untreated and EMLA-treated sites (all p < 0.001). There were no changes in time-to-peak for PORH at the untreated and EMLA-treated sites (p ≥ 0.4); however, the peak PORH response was reduced with EMLA treatment (p ≤ 0.03). The 6-week intervention increased the peak PORH at the untreated sites (p < 0.001) but not at EMLA-treated (p > 0.05) sites. Comparing the control limb before and after 6 weeks, no differences in responses occurred at either the untreated skin sites (p ≥ 0.9) or the EMLA-treated sites (p ≥ 0.9). CONCLUSIONS: Sensory nerve blockade attenuated the improvements in cutaneous vascular responses to thermal hyperaemia and PORH following chronic exposure to shear stress. These data demonstrate an important role for sensory nerve function in the initiation of vasodilatation to both PORH and thermal hyperaemia, in both the time to onset and the magnitude of vasodilatation.

Ischemia-reperfusion injury alters skin microvascular responses to local heating of the index finger.

BACKGROUND: Ischemia-reperfusion (IR) injury impairs microcirculatory function by reducing nitric oxide (NO) bioavailability and increasing sympathetic tone. This study non-invasively examined the effects of acute upper limb IR injury on local thermal hyperemia (LTH) in glabrous and non-glabrous finger skin. MATERIALS AND METHODS: In ten healthy males, LTH was examined twice (~7-10 d apart) for each skin type on the index finger using laser-Doppler flowmetry in a counterbalanced design with either 1) 20 min ischemia, followed by reperfusion (ISCH) or 2) time-matched control (SHAM). LTH tests were performed using a standard heating protocol (33-42 °C at 1 °C·20 s-1 + 20 min at 44 °C) and baseline, initial peak, nadir, delayed plateau and maximal heating phases were identified as well as vasodilatory onset time and time to initial peak. Cutaneous vasomotion was evaluated using spectral analysis and comparing absolute and normalized wavelet amplitudes between conditions for both skin types at baseline and during LTH. RESULTS: In non-glabrous skin, IR injury delayed the vasodilatory onset of local heating by 27.4 [11.3, 43.4] s (p = 0.004) and attenuated cutaneous vasodilation during the initial peak and sustained heating by -44.5 [-73.0, -15.9] PU (p = 0.003) and -34.4 [-62.9, -5.8] PU (p = 0.020), respectively. Analysis of normalized wavelet amplitudes in non-glabrous skin identified impaired microvascular function at baseline via NO-dependent mechanisms (-3.64 [-7.22, -0.05] %, p = 0.047), and during LTH via respiratory influences (-2.83 [-5.39, -0.21] %, p = 0.031). In glabrous skin, IR injury delayed vasodilatory onset time by 24.9 [1.1, 67.6] s (p = 0.042). The vasodilatory response to sustained local skin heating in glabrous skin was increased following IR injury (+56.3 [15.1, 116.5], p = 0.012), however, this was not evident when accounting for differences in blood pressure between conditions. Additionally, no other differences in vasodilatory or vasomotor functions were observed in this skin type between conditions (all, p > 0.05). CONCLUSIONS: The current IR model elicits impaired cutaneous vasodilatory responses to local heating in young males, primarily in non-glabrous skin, and may be useful for exploring mechanisms of IR-injury and for testing potential countermeasures in otherwise healthy humans.

Cutaneous neural activity and endothelial involvement in cold-induced vasodilatation.

Whether sympathetic withdrawal or endothelial dilators such as nitric oxide (NO) contributes to cold-induced vasodilation (CIVD) events is unclear. We measured blood flow and finger skin temperature (Tfinger) of the index finger in nine participants during hand immersion in a water bath at 35 °C for 30 min, then at 8 °C for 30 min. Data were binned into 10 s averages for the entire 60 min protocol for laser-Doppler flux (LDF) and Tfinger. At baseline, Tfinger was 35.3 ± 0.2 °C and LDF was 227 ± 28 PU. During hand cooling, minimum Tfinger was 10.9 ± 0.4 °C and LDF was 15 ± 4 PU. All participants exhibited at least one CIVD event (Tfinger increase ≥ 1 °C), with a mean peak Tfinger 13.2 ± 0.8 °C and a corresponding peak LDF of 116 ± 34 PU. A Morlet mother wavelet was then used to perform wavelet analysis on the LDF signal, with frequency ranges of 0.005-0.01 Hz (endothelial NO-independent), 0.01-0.02 Hz (endothelial NO-dependent), and 0.02-0.05 Hz (neurogenic). The synchronicity of wavelet fluctuations with rising LDF coincident with CIVD events was then quantified using Auto-regressive Integrated Moving Average time-series analysis. Fluctuations in neural activity were strongly synchronized in real time with increasing LDF (stationary-r2 = 0.73 and Ljung-box statistic > 0.05), while endothelial activities were only moderately synchronized (NO-independent r2 = 0.15, > 0.05; NO dependent r2 = 0.16, > 0.05). We conclude that there is a direct, real-time correlation of LDF responses with neural activity but not endothelial-mediated mechanisms. Importantly, it seems that neural activity is consistently reduced prior to CIVD, suggesting that sympathetic withdrawal directly contributes to CIVD onset.

Episodic bouts of hyperaemia and shear stress improve arterial blood flow and endothelial function.

INTRODUCTION: Exercise and heat stress lead to systemic improvements in arterial endothelial function, vascular stiffness, and cardiopulmonary capacity. The improvements in endothelial function may be primarily mediated via increases in shear stress. This study examined whether improvements in arterial function may be achieved in the absence of systemic vascular adaptations. Specifically, we hypothesized that repeated bouts of brief occlusion would improve arterial endothelial function via shear stress-dependent mechanisms. METHODS: Eleven healthy males underwent a shear stress intervention (5 s brachial occlusion, 10 s rest) for 30 min, five times weekly for 6 weeks on one arm while the other acted as an untreated control. Ultrasound was used to assess brachial arterial forearm blood flow (FBF) and vascular conductance (FVC), diameter, and shear rate (SR), while endothelial function was assessed by flow-mediated dilatation (FMD). Post-occlusive reactive hyperaemia and pulse wave velocity (PWV) were also measured. RESULTS: There were no changes in any of the measures in the control arm (all d < 0.2, p > 0.05). After 3 weeks of the intervention, FMD was increased from baseline (7.6 ± 0.6 vs. 5.9 ± 0.9%; d = 1.3, p = 0.038) and further increased after 6 weeks to 9.5 ± 2.6% (d = 1.7, p < 0.001). SR was also increased following the 6-week intervention (all d ≥ 0.6, p < 0.001). Resting and peak FBF and FVC were also increased in response to the intervention (all d ≥ 0.6, p < 0.001) and PWV was reduced. CONCLUSIONS: These data demonstrate that episodic increases in shear stress elicit marked increases in arterial endothelial function and vascular reactivity.

Effect of passive heat exposure on cardiac autonomic function in healthy children.

PURPOSE: The aim of this study was to examine the effect of passive heat stress on heart rate variability parameters in healthy children. METHOD: Fifteen children (9.3 ± 1.6 years) of both sexes (eight male) participated in two randomized experimental conditions separated by 5-12 days. Children were seated for 2 h in an environmental chamber for two sessions: neutral (22.4 ± 0.1 °C, 40.4 ± 6.5% RH) and hot (34.9 ± 0.3 °C, 36.6 ± 6.2% RH) conditions. Electrocardiogram, mean skin temperature, tympanic temperature, and blood pressure were recorded. Five min epochs were averaged for analysis of cardiac autonomic function over the 2-h protocol. RESULT: Mean skin and tympanic temperatures and heart rate increased during the hot condition (all p < 0.01) while mean arterial pressure decreased (p < 0.01). During the hot condition, root-mean-square difference of successive normal RR intervals (45 ± 9 to 38 ± 7 ms), and low- (LF, 1536 ± 464 vs. 935 ± 154 ms2) and high-frequency power (HF, 1544 ± 693 vs. 866 ± 355 ms2) decreased, whereas LF/HF ratio increased (1.64 ± 0.24 vs. 2.40 ± 0.23 au); all indices were different from neutral (all p < 0.05). These were all unchanged throughout the neutral condition (all p > 0.05), except for LF/HF ratio which decreased during the neutral condition (p < 0.05). CONCLUSION: Mild hyperthermia elicited marked changes in cardiac autonomic control in young children. These data suggest that, in healthy children, vagal withdrawal is responsible for the cardiac autonomic response to hyperthermia.

Between-day reliability of local thermal hyperemia in the forearm and index finger using single-point laser Doppler flowmetry.

OBJECTIVE: To assess between-day reliability for LTH in glabrous and nonglabrous index finger skin and nonglabrous forearm skin, with single-point laser Doppler flowmetry. METHODS: Part-1: In healthy, habitually active males (n=10), LTH was examined twice (~7-10 days apart) for both skin types on the index finger. Part-2: Identical testing was performed on the volar forearm. Local heating (33-42°C at 1°C·20 s-1  + 20 minutes at 44°C) was performed at all skin sites and baseline, initial peak, and plateau phases were identified. Data were expressed as raw CVC (laser-Doppler flux/MAP), and as CVC normalized to baseline (%CVC33°C ) and maximum heating (%CVC44°C ). Reliability was assessed using between-day mean difference, %CV, and ICC. RESULTS: Reliability (%CV) was poor at baseline for all forms of data presentation and for other phases with %CVC33°C . At the initial peak and plateau, reliability was moderate-poor (20%-26%) for CVC and good-moderate (6%-18%) for %CVC44°C . Reliability was good-moderate for vasodilatory onset time (10%-23%) and time to initial peak (6%-13%). CONCLUSIONS: For all sites, LTH reliability was acceptable for the timing, and for the initial peak and plateau using CVC or %CVC44°C .

Effect of sympathetic nerve blockade on low-frequency oscillations of forearm and leg skin blood flow in healthy humans.

OBJECTIVE: To Examine the effect of inhibiting sympathetic function on cutaneous vasomotion in the forearm and leg. METHODS: Intradermal microdialysis fibers were placed in the forearm and leg, one as an untreated control (lactated Ringer's) and the other perfused with bretylium tosylate to block sympathetic nerves. Skin blood flow was monitored using laser Doppler flowmetry. Baseline was collected for 10 minutes before local skin temperature was increased to 42°C. Spectral analysis was performed using a Morlet wavelet. RESULTS: Bretylium tosylate increased skin blood flow during baseline in the forearm (d=1.6, P<.05) and leg (d=0.5, P<.05) and decreased skin blood flow at both sites during both the initial peak (d≥1.0, P<.05) and plateau (d≥0.8, P<.05). Treatment with bretylium tosylate reduced wavelet amplitude associated with neural activity during baseline in the forearm (d=1.6, P<.05) and leg (d=0.9, P<.05). This reduction in wavelet amplitude at bretylium tosylate-treated sites was also observed during the initial vasodilation to local heating in both the forearm (d=1.6, P<.05) and leg (d=1.4, P<.05) and during the sustained vasodilation in both the forearm (d=1.6, P<.05) and leg (d=1.2, P<.05). CONCLUSIONS: Our data support that the frequency band (0.021-0.052 Hz) associated with neurogenic activity appears to be correct having a large sympathetic component.

Neuropeptide Y not involved in cutaneous vascular control in young human females taking oral contraceptive hormones.

We previously reported that the cutaneous vasodilator response to local warming in males required noradrenaline (NA) and neuropeptide-Y (NPY). Animal work has shown no role for NPY in female vascular control. We investigated the contribution of NA and NPY in human female cutaneous vascular control. Nine female and nine male participants volunteered. To elucidate whether synthetic oestrogen and progesterone altered cutaneous vascular responses, females were tested in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive pill (OCP). Skin blood flow was assessed by laser-Doppler flowmetry and expressed as cutaneous vascular conductance (CVC). Treatments were: control, combined yohimbine and propranolol (YP), BIBP-3226, and bretylium tosylate (BT). YP and BT increased basal CVC (p<0.05) relative to control sites in both HH and LH phases; though, BIBP-3226 had no effect in either phase (both p>0.05). Males basal CVC was increased at all treated sites compared to control sites (all p<0.05). YP and BT treated sites were higher in HH compared to LH (p<0.05). YP and BT treatment reduced the local warming-induced vasodilatation compared to control sites (p>0.05) in both HH and LH phases; whereas, BIBP-3226 treatment had no effect (p>0.05). In males, the vasodilatation achieved at all treated sites was reduced compared to the untreated control site (p<0.05). Data indicate that NA, not NPY, regulates basal skin blood flow and contributes to the vasodilator response to local warming in young females; however, both NA and NPY play a role in both basal and heat-induced cutaneous responses in males.

Spectral analysis of reflex cutaneous vasodilatation during passive heat stress.

Previous work has demonstrated that spectral analysis is a useful tool to non-invasively ascertain the mechanisms of control of the cutaneous circulation. The majority of work using spectral analysis has focused on local control mechanisms, with none examining reflex control. Skin blood flow was analysed using spectral analysis on the dorsal aspect of the forearm of 7 males and 7 females during passive heat stress, with mean forearm and local temperature at the site of measurement maintained at thermoneutral (33°C) to minimize the effect of local control mechanisms. Participants were passively heated to ~1.2±0.1°C above baseline rectal temperature (d=4.0, P<0.001) using a water-perfused, tube lined suit, with skin blood flow assessed using a laser-Doppler probe with an integrated temperature monitor. Spectral analysis was performed using a Morlet wavelet on the entire data set, with median power extracted during 20min of data during baseline (normothermia) and hyperthermia. Passive heat stress significantly increased laser-Doppler flux above baseline (d=4.7, P<0.001). Spectral power of the endothelial nitric oxide-independent (0.005-0.01Hz; d=1.1, P=0.004), neurogenic (0.2-0.05Hz; d=0.6, P=0.025), myogenic (0.05-0.15Hz; d=1.5, P=0.002), respiratory (0.15-0.4Hz; d=1.4 P=0.002), and cardiac (0.4-2.0Hz; d=1.1, P=0.012) frequency intervals increased with passive heat stress. In contrast, the endothelial nitric oxide-dependent frequency interval did not change (0.01-0.02Hz; d=0.3, P=0.09) with passive heat stress. These data suggest that cutaneous reflex vasodilatation is neurogenic in origin and not mediated by endothelial-nitric oxide synthase, and are congruent with invasive examinations of reflex cutaneous vasodilatation.