Skin Sympathetic Activity Research Articles

Impact of regular cold exposure on electrical skin resistance in patients with joint degenerative diseases.

Common features in chronic inflammatory disease patients (CIDP) are inflammation, mental stress (MS), and autonomic nervous system imbalance. Whole-body cryotherapy (WBC) exposure and regular physical exercise are known to regulate these features. In this study, we assessed the impact of regular physical exercise and the use of WBC exposure in CIDP on the level of electrical skin resistance (SR) to evaluate the skin sympathetic nervous activity and and estimate MS levels. SR was evaluated before and after a 10-day-period of daily physical exercise preceded or not by WBC (3 min at -110°C) in two groups of 134 CIDP (WBC vs. non-WBC groups). At baseline, the number of severe MS patients was similar in both groups. However, after the training period, the number of severe MS patients significantly decreased in the WBC group, only. An increase in SR (a decrease in stress level) was noted in the WBC group only, and such increase was higher in men than in women and in patients younger than 60 versus patients older than 60 years old. The use of daily WBC combined with physical exercise induced physiological adaptations and lowered the sympathetic nervous activity that may reflect a reduced level of MS in CIDP. These adaptations seem to depend on gender and age.

Evaluation of skin sympathetic nervous activity for classification of intracerebral hemorrhage and outcome prediction

Classification and outcome prediction of intracerebral hemorrhage (ICH) is critical for improving the survival rate of patients. Early or delayed neurological deterioration is common in ICH patients, which may lead to changes in the autonomic nervous system (ANS). Therefore, we proposed a new framework for ICH classification and outcome prediction based on skin sympathetic nervous activity (SKNA) signals. A customized measurement device presented in our previous papers was used to collect data. 117 subjects (50 healthy control subjects and 67 ICH patients) were recruited for this study to obtain their 5-min electrocardiogram (ECG) and SKNA signals. We extracted the signal's time-domain, frequency-domain, and nonlinear features and analyzed their differences between healthy control subjects and ICH patients. Subsequently, we established the ICH classification and outcome evaluation model based on the eXtreme Gradient Boosting (XGBoost). In addition, heart rate variability (HRV) as an ANS assessment method was also included as a comparison method in this study. The results showed significant differences in most features of the SKNA signal between healthy control subjects and ICH patients. The ICH patients with good outcomes have a higher change rate and complexity of SKNA signal than those with bad outcomes. In addition, the accuracy of the model for ICH classification and outcome prediction based on the SKNA signal was more than 91% and 83%, respectively. The ICH classification and outcome prediction based on the SKNA signal proved to be a feasible method in this study. Furthermore, the features of change rate and complexity, such as entropy measures, can be used to characterize the difference in SKNA signals of different groups. The method can potentially provide a new tool for rapid classification and outcome prediction of ICH patients.Index Terms—intracerebral hemorrhage (ICH), skin sympathetic nervous activity (SKNA), classification, outcome prediction, cardiovascular and cerebrovascular diseases.

A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study

Nattokinase (NK) intake may improve blood flow; however, its effects on skin temperature, which is predominantly controlled by skin surface blood flow, are unknown. The purpose of this study was to determine the effects of a single dose of NK on changes in skin temperature after cold water immersion. A double-blinded, placebo-controlled, crossover intervention study was performed on nine healthy men. The participants were randomised to receive either a single dose of 2,000 fibrinolytic units (FU) of NK or a placebo with subsequent crossover. Two hours after supplementation, the participants immersed both hands in a water bath maintained at 10 °C for 1 min. Skin temperature, perceived coldness, cardiac output, and sympathetic nervous activity were measured before, during, and after water immersion. Two-way analysis of variance showed a significant effect of treatment interaction on the skin temperature of the middle finger, palm, and back of the right hand (p < 0.05). These findings represented that the skin temperatures of the middle finger, palm, and back of the right hand immersed in the cold water were significantly dropped due to the cold water immersion, and then recovered more quickly by NK intake than by placebo intake. The results of the current study highlight the potential implications of NK for the prevention of excessive vasoconstriction. It may be more significant for those with cold-sensitive constitution, such as women and elderly. In contrast, the acute administration of 2,000 FU of NK did not affect changes in heart rate, cardiac output, sympathetic nervous activity compared with a placebo in healthy men.

Application of Physiological Autonomic Activity Tracking GUI and Computational Algorithms for Measuring Persistent Vagal Nerve Dysfunction After Recovery from SARS‐CoV‐2 Infection

Post‐Acute Sequelae of SARS‐CoV‐2 infection (PASC) is now recognized as a constellation of symptoms such as postural hypotension, anxiety, and “brain fog” in addition to autonomic nervous system dysfunction such as tachycardia and labile hypertension. Better quantification of these conditions, specifically, autonomic nervous system dysfunction, is desired for future diagnostics, treatment modalities, and gaining a further understanding of PASC. This research has led to application of a novel autonomic activity tracking algorithm and GUI suite from previous work, see Figure 1, to study the physiological autonomic activity in six patients who had recovered from acute SARS‐CoV‐2 infection a mean of six months prior but were still experiencing symptoms. By measuring skin sympathetic nervous activity (SKNA), heart rate variability, and the cutaneous electrogastrogram (EGG), all before and after a water meal challenge, the data was fed into a custom analysis pipeline, shown in Figure 1. Each of the PASC patients were compared to a mean response of 34 healthy controls, each undergoing a 20‐minute baseline recording and another 20‐minute recording after ingestion of an 8 oz water test meal. All six patients showed significantly abnormal heart rate variability on frequency domain analysis in predominantly the low frequency (LF) and very low frequency (VLF) bands, and less so in the high frequency (HF) band, suggesting sympathetic nerve dysfunction. Three patients showed a significant decrease in SKNA while two showed a significant increase. All patients showed an abnormal cutaneous EGG. As shown in Figure 2, the temporal responses of aSKNA, VLF, LF, HF, and EGG for the PASC patients revealed that on average they were statistically different (p<0.05) from the healthy controls’ responses respectively during 98.4%, 78.4%, 86.76%, 47.9%, and 86.1% of the 40‐minute time period in testing, 20 minutes of baseline and 20 minutes after ingestion. In conclusion, we are looking at the sympathetic, parasympathetic, and enteric nervous systems synced temporally for applications with classification and further stratification of PASC based on the temporal dynamics of their autonomic nervous system mediated coordination from digestion. This shows that SARS‐CoV02 infection appears to have a significant effect on sympathetic and parasympathetic autonomic nervous system function and may be responsible for the disturbances noted in PASC. This work provides the framework and example of use for further applications in autonomic disorder physiological response exploration and furthermore can be expanded to other areas of neuromodulation.

Thermoregulatory reflex control of cutaneous vasodilation in healthy aging

ABSTRACT Reflex cutaneous vasodilation during heating is attenuated in healthy human aging secondary to blunted increases in efferent skin sympathetic nervous system activity (SSNA) and reductions in end-organ sensitivity. Whether age-related alterations in the mean body temperature ( b) threshold for increasing SSNA and/or the sensitivity of responses are evident with aging have not been examined. We tested the hypotheses that the Tb threshold for SSNA and cutaneous vascular conductance (CVC) would be increased, but the sensitivity would be reduced, with aging. Reflex vasodilation was induced in 13 young (23 ± 3 y) and 13 older (67 ± 7 y) adults using a water-perfused suit to systematically increase mean skin and esophageal temperatures. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome were continuously measured. SSNA was normalized to baseline; CVC was normalized as a percentage of maximal CVC. Baseline b was lower in older adults (36.0 ± 0.4°C vs 36.4 ± 0.3°C; p = 0.005). During passive heating, the ∆ b thresholds for increasing SSNA and CVC were greater (1.3 ± 0.4°C vs 0.9 ± 0.3°C; p = 0.007 and 1.3 ± 0.4°C vs 0.8 ± 0.3°C; p = 0.002, respectively) in older adults. The slope of the relation between both SSNA (0.31 ± 0.23 vs 0.13 ± 0.10 V⋅s⋅°C −1; p = 0.01) and CVC (87.5 ± 50.1 vs 32.4 ± 18.1%max⋅°C−1; p = 0.002) vs b was lower in older adults. The relative b threshold for activation of SSNA and the initiation of reflex cutaneous vasodilation is higher in older adults, and once activated, the sensitivity of both responses is diminished, supporting the concept that the efferent component of the thermoregulatory reflex arc is impaired in healthy aging. Abbreviations: CI: confidence interval; CVC: cutaneous vascular conductance; SSNA: skin sympathetic nervous system activity; b: mean body temperature; Tes: esophageal temperature; sk: mean skin temperature.

Horticultural Activity: Its Contribution to Stress Recovery and Wellbeing for Children.

In recent years, children’s use of mobile phones has grown rapidly, which might lead to an increase in mental stress and negatively affect their health. Despite increasing evidence that horticultural activity can provide significant health benefits, few scientific evidence-based studies are currently available regarding these benefits to children’s health and wellbeing in schools. Therefore, this study aims to determine the potential benefits of horticultural activity for children from both psychological and physiological perspectives. Twenty-six elementary school students (mean age, 8.12 ± 0.21 years) were asked to perform a plant-related task and a mobile game task for 5 min. During both tasks, physiological sensors were used to measure the participants’ heart rate variability, skin conductance, and skin temperature. Additionally, the participants’ emotional responses were assessed using semantic differential and State–Trait Anxiety Inventory tests immediately after each task. Results revealed that, compared with the mobile game task, participants’ health statuses were positively correlated with the horticultural task, including a considerable decrease in skin conductance and sympathetic nervous activity, together with a marginal increase in parasympathetic nervous activity. Such responses suggested that horticultural activity increased relaxation and decreased feelings of stress. Furthermore, the horticultural activity was associated with a substantial increment in comfort, naturalness, relaxation, and cheerfulness feelings, as well as a significant reduction in depression and a reduction in total anxiety levels. Given these positive benefits, horticultural activity may provide a great contribution to children’s healthy life at school, prompt psychological relaxation and minimize mental stress relative to smartphone games.

Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.

Impairments in both central sympathetic and peripheral microvascular function contribute to blunted reflex cutaneous vasodilatation during heat stress in healthy older adults. Hypercholesterolaemia is associated with decrements in neurovascular function; however, little is known about the impact of hypercholesterolaemia on the integrated responses to heat stress. Further, whether chronic statin therapy alters skin sympathetic outflow or its relation to cutaneous vascular conductance during heat stress is unknown. We demonstrate that reflex cutaneous vasodilatation is impaired in older hypercholesterolaemic adults but not in formerly hypercholesterolaemic adults currently treated with a statin compared to age-matched controls. Additionally, chronic statin treatment-induced improvements in reflex vasodilatation are mediated, in part, by increases in end-organ responsiveness to efferent sympathetic outflow during whole-body heating. These data add to the growing body of literature substantiating the beneficial pleiotropic neurovascular effects of chronic statin treatment and provide further support for the use of statins to confer additional cardioprotective benefits in older adults. Attenuated reflex cutaneous vasodilatation in healthy human ageing is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolaemia is associated with further impairments in neurovascular function. HMG-CoA reductase inhibitors (statins) improve cutaneous endothelium-dependent dilatation; however, whether statin therapy alters skin sympathetic nervous system activity (SSNA) or its relation to cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolaemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilatation in response to a 1.0°C rise in oral temperature (Tor ; water perfused suit) was induced in 13 healthy normocholesterolaemic adults (62±2years; LDL=113±7mg/dl), 10 hypercholesterolaemic adults (60±1years; LDL=183±2mg/dl), and 10 previously hypercholesterolaemic adults (64±1years; LDL=102±2mg/dl) treated with lipophilic statin (10-40mg daily). SSNA (peroneal microneurography) and red cell flux (laser-Doppler flowmetry) in the innervated dermatome (dorsum of foot) were continuously measured. Reflex vasodilatation was blunted in hypercholesterolaemic adults, but not in statin-treated adults, compared to normocholesterolaemic adults (at ∆Tor =1.0°C: normal=36±1%CVCmax , high=32±1%CVCmax , statin=38±1%CVCmax ; P<0.01). ∆SSNA was not different (at ∆Tor =1.0°C: normal: ∆=393±96%, high: ∆=311±120%, statin: ∆=256±90%; P=0.11). The slope of the SSNA:CVC relation was blunted in hypercholesterolaemic adults (0.02±0.03%CVCmax /%baseline ) compared to both normocholesterolaemic (0.09±0.02%CVCmax /%baseline ; P=0.024) and statin-treated (0.12±0.05%CVCmax /%baseline ; P=0.03) adults. Chronic statin treatment improves reflex cutaneous vasodilatation in formerly hypercholesterolaemic older adults by increasing end-organ responsiveness to sympathetic outflow during passive heat stress.

P66-T Skin sympathetic activity and autonomic studies in ross and harlequin syndrome

Background Ross syndrome is a degenerative disorder characterized by the clinical triad of tonic pupil, hyporeflexia and segmental anhidrosis. Harlequin syndrome is described as segmental anhidrosis without ocular sympathetic deficit. Harlequin syndrome exhibits a selective abnormality in the peripheral skin sympathetic nerves and Ross syndrome reveals a widespread autonomic dysfunction. We present 4 patients with sudomotor dysfunction and different patterns of autonomic abnormalities. Material and methods Patients 1 and 2 complained of unilateral facial and upper limb flushing and sweating impairment. Patients 3 and 4 complained of an extensive anhidrosis and compensatory hyperhidrosis, patient 4 also presented an Adie’s pupil. Patients underwent nerve conduction studies, sympathetic skin responses (SSR), cardiovascular reflexes (deep breathing, Valsalva maneuver and standing) and laser evoked potentials. Results SSR were absent in the anhidrotic upper limb in patients 1 and 2, either to electric or laser stimuli. No evoked SSR responses were recorded in the four limbs in patients 3 and 4. Patient 4 presented slightly impaired cardiovascular reflexes and patients 2 and 4 presented mild abnormalities in sensory nerve conduction studies. Serologic screening, brain MRI and cervicothoracic CT were normal in all patients. Patients 1 and 2 were affected by a Harlequin syndrome, patient 3 presented an uncompleted Ross syndrome and patient 4 a classic Ross syndrome. Conclusions Ross and Harlequin syndrome are two clinically distinguishable expressions of partial dysautonomias belonging to a degenerative autonomic disorder that involves sympathetic, parasympathetic and myelinated nerve fibres with different distribution, extent and degree of impairment.

Statin Therapy Enhances Reflex Cutaneous Vasodilation in Formerly Hypercholesterolemic Older Adults by Improving Neurovascular Coupling

Reflex cutaneous vasodilation is attenuated in healthy human aging and is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolemia, a primary risk factor for cardiovascular disease, is associated with increased sympathetic nervous system activity and further impairments in endothelial function. Independent of their lipid‐lowering effect, HMG‐CoA reductase inhibitors (statins) – the most commonly prescribed medication in the U.S. – reduce sympathetic outflow and augment endothelium‐dependent dilation. However, whether statin therapy improves the relation between skin sympathetic nervous system activity (SSNA) and cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilation was induced in 13 healthy normocholesterolemic older adults [62±2 yrs; low‐density lipoprotein (LDL) 113±7 mg/dl), 10 hypercholesterolemic older adults (60±1 yrs; LDL 183±2 mg/dl), and 10 previously hypercholesterolemic older adults now treated with a lipophilic statin (10–40 mg daily) to normalize LDL (64±1 yrs; LDL 102±2 mg/dl) using a water‐perfused suit to elevate oral temperature (Tor) by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline and CVC was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating to 43°C). Mean arterial pressure, baseline CVC, and maximal CVC were not significantly different among groups (all p&gt;0.05). During passive heating, the increase in SSNA was not different among groups (normal: Δ=393±96%, high: Δ=311±120%, and statin: Δ=256±90%; p=0.11). Reflex vasodilation was blunted in hypercholesterolemic adults, but not in statin‐treated adults, compared to normocholesterolemic adults (normal: 36±1%CVCmax, high: 32±1%CVCmax, and statin: 38±1%CVCmax respectively, at ΔTor=1.0°C; p&lt;0.01). There were no differences among groups for the slope of the ΔSSNA:ΔCVC relation (normal: 0.06±0.00, high: 0.07±0.01, and statin: 0.07±0.01, p=0.91); however, this relation was shifted upward in statin‐treated adults (y‐intercept; normal: 3.1±0.9, high: 4.0±0.9, and statin: 7.3±1.3; p=0.001). These data demonstrate that chronic statin treatment improves reflex cutaneous vasodilation in formerly hypercholesterolemic older adults, in part via increases in end‐organ responsiveness to sympathetic outflow during passive heat stress.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome.

Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (β=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (β=3.1±1.3, p=0.018). Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. CWP is associated with activated stress markers that may deteriorate sleep.

Measuring and quantifying skin sympathetic nervous system activity in humans

Development of the technique of microneurography has substantially increased our understanding of the function of the sympathetic nervous system (SNS) in health and in disease. The ability to directly record signals from peripheral autonomic nerves in conscious humans allows for qualitative and quantitative characterization of SNS responses to specific stimuli and over time. Furthermore, distinct neural outflow to muscle (MSNA) and skin (SSNA) can be delineated. However, there are limitations and caveats to the use of microneurography, measurement criteria, and signal analysis and interpretation. MSNA recordings have a longer history and are considered relatively more straightforward from a measurement and analysis perspective. This brief review provides an overview of the development of the technique as used to measure SSNA. The focus is on the utility of measuring sympathetic activity directed to the skin, the unique issues related to analyzing and quantifying multiunit SSNA, and the challenges related to its interpretation.

Folic acid supplementation increases cutaneous vasodilator sensitivity to sympathetic nerve activity in older adults.

During heat stress, blunted increases in skin sympathetic nervous system activity (SSNA) and reductions in end-organ vascular responsiveness contribute to the age-related reduction in reflex cutaneous vasodilation. In older adults, folic acid supplementation improves the cutaneous vascular conductance (CVC) response to passive heating; however, the influence of folic acid supplementation on SSNA:CVC transduction is unknown. Fourteen older adults (66 ± 1 yr, 8 male/6 female) ingested folic acid (5 mg/day) or placebo for 6 wk in a randomized, double-blind, crossover design. In protocol 1, esophageal temperature (Tes) was increased by 1.0°C (water-perfused suit) while SSNA (peroneal microneurography) and red cell flux in the innervated dermatome (laser Doppler flowmetry; dorsum of the foot) were continuously measured. In protocol 2, two intradermal microdialysis fibers were placed in the skin of the lateral calf for graded infusions of acetylcholine (ACh; 10-10 to 10-1 M) with and without nitric oxide synthase (NOS) blockade (20 mM nitro-l-arginine methyl ester). Folic acid improved reflex vasodilation (46 ± 4% vs. 31 ± 3% CVCmax for placebo; P < 0.001) without affecting the increase in SSNA (Δ506 ± 104% vs. Δ415 ± 73% for placebo; NS). Folic acid increased the slope of the SSNA-to-CVC relation (0.08 ± 0.02 vs. 0.05 ± 0.01 for placebo; P < 0.05) and extended the response range. Folic acid augmented ACh-induced vasodilation (83 ± 3% vs. 66 ± 4% CVCmax for placebo; P = 0.002); however, there was no difference between treatments at the NOS-inhibited site (53 ± 4% vs. 52 ± 4% CVCmax for placebo; NS). These data demonstrate that folic acid supplementation enhances reflex vasodilation by increasing the sensitivity of skin arterioles to central sympathetic nerve outflow during hyperthermia in aged human subjects.

Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous vasoconstriction in human hypertension.

In hypertensive adults (HTN), cardiovascular risk increases disproportionately during environmental cold exposure. Despite ample evidence of dysregulated sympathetic control of the peripheral vasculature in hypertension, no studies have examined integrated neurovascular function during cold stress in HTN. The findings of the present study show that whole-body cold stress elicits greater increases in sympathetic outflow directed to the cutaneous vasculature and, correspondingly, greater reductions in skin blood flow in HTN. We further demonstrate an important role for non-adrenergic sympathetic co-transmitters in mediating the vasoconstrictor response to cold stress in hypertension. In the context of thermoregulation and the maintenance of core temperature, sympathetically-mediated control of the cutaneous vasculature is not only preserved, but also exaggerated in hypertension. Given the increasing prevalence of hypertension, clarifying the mechanistic underpinnings of hypertension-induced alterations in neurovascular function during cold exposure is clinically relevant. Despite ample evidence of dysregulated sympathetic control of the peripheral vasculature in hypertension, no studies have examined integrated neurovascular function during cold stress in hypertensive adults (HTN). We hypothesized that (i) whole-body cooling would elicit greater cutaneous vasoconstriction and greater increases in skin sympathetic nervous system activity (SSNA) in HTN (n=14; 56±2years) compared to age-matched normotensive adults (NTN; n=14; 55±2years) and (ii) augmented reflex vasoconstriction in HTN would be mediated by an increase in cutaneous vascular adrenergic sensitivity and a greater contribution of non-adrenergic sympathetic co-transmitters. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (water-perfused suit). Sympathetic adrenergic- and non-adrenergic-dependent contributions to reflex cutaneous vasoconstriction and vascular adrenergic sensitivity were assessed pharmacologically using intradermal microdialysis. Cooling elicited greater increases in SSNA (NTN: +64±13%baseline vs. HTN: +194±26%baseline ; P<0.01) and greater reductions in skin blood flow (NTN: -16±2%baseline vs. HTN: -28±3%baseline ; P<0.01) in HTN compared to NTN, reflecting an increased response range for sympathetic reflex control of cutaneous vasoconstriction in HTN. Norepinephrine dose-response curves showed no HTN-related difference in cutaneous adrenergic sensitivity (logEC50 ; NTN: -7.4±0.3log Mvs. HTN: -7.5±0.3log M; P=0.84); however, non-adrenergic sympathetic co-transmitters mediated a significant portion of the vasoconstrictor response to cold stress in HTN. Collectively, these findings indicate that hypertension increases the peripheral cutaneous vasoconstrictor response to cold via greater increases in skin sympathetic outflow coupled with an increased reliance on non-adrenergic neurotransmitters.

Abstract 11874: Sympathetic Control of Reflex Cutaneous Vasoconstriction in Human Hypertension

Introduction: Cardiovascular-related morbidity and mortality during environmental cold exposures increase disproportionally in hypertensive (HTN) adults. Although alterations in central control of sympathetic outflow and peripheral regulation of vascular function are evident in hypertension and contribute to increased cardiovascular risk, no studies have examined sympathetic control of reflex cutaneous vasoconstriction during cold stress in humans with hypertension. We hypothesized that 1) whole-body cold stress would elicit exaggerated increases in skin sympathetic nervous system activity (SSNA) and greater reductions in skin blood flow in HTN [n=10; 56±3 yrs; resting blood pressure (BP) 145±7/84±3 mmHg] compared to normotensive adults (NTN; n=12, 55±3 yrs; resting BP 126±4/79±3 mmHg) and 2) cutaneous adrenergic sensitivity would be increased in HTN adults. Methods: In Protocol 1, reflex vasoconstriction was induced by gradual whole-body cooling (to a mean skin temperature of 30.5°C) using a water-perfused suit. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured continuously. SSNA was expressed as a percent change from baseline. In Protocol 2, an intradermal microdialysis fiber was placed in the skin of the lateral calf to measure red cell flux in response to graded intradermal infusions of norepinephrine (NE; 10 -12 to 10 -2 M). In each study, cutaneous vascular conductance (CVC=flux/mean arterial pressure) was expressed as a change from baseline. Results: During cooling, HTN exhibited greater increases in SSNA compared to NTN adults (Δ = 194±26% HTN vs. 51±12% NTN; P&lt;0.01) but cutaneous vasoconstriction was not different between groups (ΔCVC base = -0.03±0.003 ητν vs. -0.02±0.01 flux units mmHg -1 NTN; P=0.97). The slope of the relation between ΔSSNA and ΔCVC base during cold stress was blunted in HTN adults (P&lt;0.01). There was no group difference in cutaneous adrenergic responsiveness to exogenous NE (dose-response logEC 50 ; -7.2±0.2 HTN vs. -7.5±0.4 NTN; P=0.75). Conclusion: Although cutaneous microvascular adrenergic responsiveness to NE is preserved, the sensitivity of the sympathetic reflex response to whole-body cold stress is diminished in human hypertension.

Blunted increases in skin sympathetic nerve activity are related to attenuated reflex vasodilation in aged human skin.

Reflex cutaneous vasodilation in response to passive heating is attenuated in human aging. This diminished response is mediated, in part, by age-associated reductions in endothelial function; however, the contribution of altered skin sympathetic nervous system activity (SSNA) is unknown. We hypothesized that 1) healthy older adults would demonstrate blunted SSNA responses to increased core temperature compared with young adults and 2) the decreased SSNA response would be associated with attenuated cutaneous vasodilation. Reflex vasodilation was elicited in 13 young [23 ± 1 (SE) yr] and 13 older (67 ± 2 yr) adults using a water-perfused suit to elevate esophageal temperature by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating, 43°C). Reflex vasodilation was attenuated in older adults (P < 0.001). During heating, SSNA increased in both groups (P < 0.05); however, the response was significantly blunted in older adults (P = 0.01). The increase in SSNA during heating was linearly related to cutaneous vasodilation in both young (R2 = 0.87 ± 0.02, P < 0.01) and older (R2 = 0.76 ± 0.05, P < 0.01) adults; however, slope of the linear regression between ΔSSNA and ΔCVC was reduced in older compared with young (older: 0.05 ± 0.01 vs. young: 0.08 ± 0.01; P < 0.05). These data demonstrate that age-related impairments in reflex cutaneous vasodilation are mediated, in part, by blunted efferent SSNA during hyperthermia.

Interrelations between electrodermal activity and internal diseases

The article deals with a new medical technhique for the assessment of autonomic regulation of internal systems and skin. We suggest investigating skin sympathetic nervous activity by the method of electrodermal testing of skin sympathetic reactions. It has been showed that current of 200-250 microamperes and 12 volts is optimal for testing the skin sympathetic responses in adult patients. We observed 12 groups of patients with various diseases and a control group of apparently healthy people. Each of the experimental groups consisted of people with severe or moderately severe pathology of a certain type of visceral system which caused significant functional or structural disorders in the tissue of some organ. The study carried out on distal extremities revealed 12 pairs of skin segments of vegetative support; we suggested a conception of vegetotome--a site of embryonic development of the autonomic nervous system, which provides single autonomic innervation of individual sections of meso-, ento- and ectoderm.

Effects of pressure applied during standardized spinal mobilizations on peripheral skin blood flow: A randomised cross-over study

BackgroundPeripheral skin blood flow (SBF) changes during and after spinal mobilization (SM), evaluated with laser Doppler flowmetry, may document physiological responses associated with SM. ObjectivesTo document variations in SBF during and after application of an SM and evaluate influence of pressure on SBF by applying the same standardized SM with 3 different nonnoxious pressures. DesignCross-over design with 4 interventions on 4 different days: control (no touch) and 3 SMs applied rhythmically at 5%, 40%, or 80% of pain pressure threshold (sham SM, low-pressure SM, or high-pressure SM, respectively). MethodThirty-two individuals participated. The inspiratory gasp (IG) test was our positive control of vasoconstriction through excitation of the skin sympathetic nervous activity (SSNA). Each session comprised 5 phases: (1) baseline at the end of a 20-min acclimatization, (2) IG test, (3) post-IG phase, (4) SM phase or no manual contact for control, and (5) post-SM phase. A Biopac MP36 system collected SBF data, and a Novel Pliance-X system recorded pressure data. Results/findingsEqual and significant bilateral vasodilation occurred during application of unilateral sham SM, low-pressure SM, and high-pressure SM. Post-SM significant vasodilation persisted after high-pressure SM. ConclusionsThe current study is the first to describe bilateral peripheral SBF changes occurring during and 5 min after application of standardized SMs. Our post-SM vasodilation suggests involvement of mechanisms other than the putative SSNA-excitatory mechanism proposed with skin conductance measurements. Persistence of post-SM vasodilation following only high-pressure SM suggests possible pressure-dependent mechanisms. However, further research is warranted to clarify our findings.

Reflex Control of Cutaneous Vasoconstriction during Whole‐body Cooling in Aged Humans

Reflex cutaneous vasoconstriction (VC) is impaired in human aging; however, the relative causative contributions of altered skin sympathetic nervous system activity (SSNA), signal transduction, and end‐organ responsiveness are unclear. We hypothesized that 1) whole‐body cold stress would elicit blunted SSNA responses in healthy older (O) compared to young (Y) adults and 2) cutaneous adrenergic responsiveness would be reduced in O adults. 10 Y (24±1 yrs) and 11 O adults (57±2 yrs) participated in two protocols. In Protocol 1, reflex VC was induced by gradual whole‐body cooling (mean skin temperature = 30.5°) using a water‐perfused suit. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured continuously. SSNA was expressed as a percentage of baseline. In Protocol 2, an intradermal microdialysis fiber was placed in the skin of the lateral calf to measure red cell flux in response to graded intradermal infusions of norepinephrine (NE; 10‐12 to 10‐2 M). In each study, cutaneous vascular conductance (CVC=flux/mean arterial pressure) was expressed as a change from baseline. Reflex cutaneous VC was attenuated in O adults (‐0.034±0.01 Y v. ‐0.018±0.01 O ΔCVCbase; P&lt;0.05). SSNA increased during cooling in Y (273±37%; P&lt;0.05) but not O adults (143±10%; P&gt;0.05). There was no age‐related difference in cutaneous adrenergic responsiveness to exogenous NE (dose‐response logEC50; ‐6.6±0.4 Y vs. ‐7.0±0.3 O; P=0.57). These data demonstrate that age‐related impairments in reflex cutaneous VC are mediated in part by blunted SSNA responses and not by reduced cutaneous adrenergic responsiveness, suggesting that presynaptic synthesis and/or SSNA‐mediated release of vesicular NE is decreased in aged skin.

Sympathetic and cardiovascular changes during sleep in narcolepsy with cataplexy patients

ObjectiveNeural mechanisms underlying sleep-onset rapid eye movement (REM) periods (SOREMPs) in narcolepsy and the role of hypocretin in driving sympathetic changes during sleep are misunderstood. We aimed to characterize autonomic changes during sleep in narcolepsy with cataplexy (NC) patients to clarify the nature of SOREMP events and the effect of hypocretin deficiency on sympathetic activity during sleep. MethodsWe observed 13 hypocretin-deficient NC patients and five healthy controls who underwent nocturnal video-polysomnography (v-PSG) with blood pressure (BP) recording, heart rate (HR), skin sympathetic activity (SSA), and muscle sympathetic nerve activity (MSNA) from the peroneal nerve by microneurography. ResultsCompared to wake, control participants displayed a progressive significant decrease of BP and sympathetic activities during nonrapid eye movement (NREM) sleep and an increase of autonomic activity during REM sleep, as expected. NC patients showed: (1) a decrease of sympathetic activities during SOREMP comparable to NREM sleep stage 1 (N1) but in contrast to the increased activity typical of REM sleep; and (2) physiologic sympathetic change during the following sleep stages with a progressive decrease during NREM sleep stage 2 (N2) and NREM sleep stage 3 (N3) and a clear increase in REM sleep, though BP did not show the physiologic decrease during sleep (nondipper pattern). ConclusionsSOREMPs in NC patients lack the sympathetic activation occurring during physiologic REM sleep, thus suggesting a dissociated REM sleep condition. In addition, our data indicated that hypocretin plays a limited role in the regulation of sympathetic changes during sleep.

Skin sympathetic vasoconstrictor response to static maximum inspiratory breath-holds: effects of breath-hold duration

Objective To quantify the temporal changes in the volume of blood flow to the skin of the forearm and lower leg during static maximum inspiratory breath-holding of different durations.Methods Blood flow to the skin of the forearm and lower leg were continuously measured with laser Doppler flowmetry in 12 healthy subjects.They were randomly selected to hold their breath for 10,20 or 40 seconds,or as long as possible.The volume of skin blood flow,the onset latency and the recovery latency were measured before,during and after the breath holding.Results Blood flow decreased significantly during each breath-hold with any durations.The magnitude of the decrease and its latencies were similar with all the durations.The average volume of skin blood flow and it's minimum value during each breath-hold were significantly lower in the forearms than in the lower legs.However,the average onset latency (4.41 ±0.44 s) and the average recovery latency (5.95 ±0.59 s) in the forearms were significantly shorter than in the lower legs (4.83 ± 0.70 s for onset and 7.33 ± 0.91 s for recovery).Conclusion The volume of skin blood flow decreases during a static maximum inspiratory breath-hold,and the magnitude of the increase is not related to the duration of the breath-hold.The generalized increase in skin sympathetic vasoconstrictor activity during a static breath-hold is greater in the forearm than in the lower leg. Key words: Static breath holding; Laser doppler flowmetry; Sympathetic vasoconstriction; Skin; Blood flow