Nonglabrous Skin Research Articles

Evaluating transient phenomena by wavelet analysis: early recovery to exercise.

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role.NEW & NOTEWORTHY We address the applicability of wavelet analysis (WA) in evaluating transient phenomena on a model of early recovery to exercise, which is the only exercise-associated phase characterized by a distinct transient shape and as such cannot be assessed using conventional tools. Our WA-based algorithm provided a reliable spectral decomposition of laser-Doppler (LD) signals in early recovery, enabling us to speculate roughly on the mechanisms involved in the regulation of skin microcirculation in this phase.

In vivo pressure-flow relation of human cutaneous vessels following prolonged iterative exposures to hypergravity.

The study examined intra- and interlimb variations in cutaneous vessel responsiveness to acute and repeated transmural pressure elevations. In 11 healthy men, red blood cell flux was assessed via laser-Doppler flowmetry on both glabrous and nonglabrous skin regions of an arm (finger and forearm) and leg (toe and lower leg), across a wide range of stepwise increasing distending pressures imposed in the vessels of each limb separately. The pressure-flux cutaneous responses were evaluated before and after 5 wk of intermittent (40 min, 3 sessions per week) exposures to hypergravity (∼2.6-3.3 G; G training). Before and after G training, forearm and lower leg blood flux were relatively stable up to ∼210 and ∼240 mmHg distending pressures, respectively; and then they increased two- to threefold (P < 0.001). Finger blood flux dropped promptly (P < 0.001), regardless of the G training (P = 0.64). At ≤120-mmHg distending pressures, toe blood flux enhanced by ∼40% (P ≤ 0.05); the increase was augmented after the G training (P = 0.01). At high distending pressures, toe blood flux dropped by ∼70% in both trials (P < 0.001). The present results demonstrate that circulatory autoregulation is more pronounced in glabrous skin than in nonglabrous skin, and in nonglabrous sites of the leg than in those of the arm. Repetitive high-sustained gravitoinertial stress does not modify the pressure-flow relationship in the dependent skin vessels of the arm nor in the nonglabrous sites of the lower leg. Yet it may partly inhibit the myogenic responsiveness of the toe's glabrous skin.

Regional Differences in Human Skin Responses to Receptor Agonists: Implications for Differing Facial vs. Forearm Innervation

There is not yet consensus on the precise differences between non-glabrous and facial skin characteristics. Our lab identified similar responses to local heat stress in forearm and facial skin, while others identified differing responses to autonomic stressors within facial regions. Anatomical differences, such as the thinner nature of facial skin and specifically its thinner stratum corneum, may also impact facial autonomic responses. Considering this layer is a protective barrier, facial skin may be more sensitive to perturbations like drug administration. While non-glabrous skin is innervated by spinal nerves, facial skin is innervated by cranial nerves. Because of these anatomical and physiological differences between non-glabrous and facial skin, it is possible that their differing neural and receptor characteristics impact a key autonomic end-organ response: cutaneous blood flow. In this pilot experiment, we investigated possible regional differences between the forehead and forearm in response to adrenergic and cholinergic agonists. We hypothesized that drugs targeting adrenergic (phenylephrine, clonidine, and isoproterenol) and cholinergic (acetylcholine) cutaneous receptors would elicit similar vasomotor effects in both locations. One female subject underwent forearm and forehead iontophoresis of each agonist using adaptations of published protocols, as well as a control protocol using deionized water (vehicle) alone. We recorded blood flow via laser-Doppler flowmetry (Moor Instruments) and beat-by-beat arterial blood pressure via finger photoplethysmography (ADInstruments). We calculated baseline cutaneous vascular conductance (CVC) and plateau 43°C CVC to determine the change in skin blood flow resulting from drug administration. Our results indicate that while phenylephrine administration caused vasodilation, opposing our hypothesis, administration of all other drugs caused responses in agreement with our expectations. Thus, these pilot data suggest that facial and non-glabrous skin may respond similarly to adrenergic or cholinergic agonists. These findings imply a potential use for topical dermatological drug treatments utilized on the trunk/extremities to benefit cutaneous facial diseases.

Cutaneous iontophoresis of adrenergic agonists can mimic in vivo neural effects on vasodilation

Iontophoresis utilizes electrical current to non-invasively deliver agents through the skin. This pilot study sought to determine if iontophoresis could be paired with laser Doppler flowmetry (LDF) to administer adrenergic and cholinergic agonists and measure the subsequent changes in cutaneous blood flow. We hypothesized that iontophoresis administration would produce vascular tone changes consistent with those seen during other delivery methods. We iontophoresed phenylephrine, clonidine, isoproterenol, and acetylcholine to the forearm of one generally healthy 44-year-old female using existing or adapted protocols. We also created half-strength protocols with the goal of establishing dose-response relations. We quantified erythrocyte flux via LDF and beat-by-beat arterial blood pressure via finger photoplethysmography. After baseline, each drug was administered using its half and full-strength protocols, separated by a washout period. Finally, we stimulated maximal blood flow at each iontophoresis site via non-noxious local heating to 43°C. Cutaneous vascular conductance (CVC; laser Doppler flux/ mean arterial pressure) was calculated during baseline and following iontophoresis. We administered vehicle (deionized water) alone as a control, using the same protocols and analysis. The drug responses generally matched our predictions with the exception of phenylephrine, which caused vasodilation. Vehicle administration also caused vasodilation. Full-strength application generally led to a more pronounced change in CVC, suggesting that a dose-response relation might be established with additional data. Applications of certain agents led to a higher CVC than “maximal”, possibly raising the need to alter the method for establishing maximal cutaneous blood flow. Overall, our findings indicate that iontophoresis and LDF can be used to effectively administer adrenergic and cholinergic agonists to non-glabrous skin and affect vascular tone. This non-invasive technique could be used to investigate responses to these agents in those whose cutaneous neural receptor characteristics have been altered as a consequence of disease.

Remote Photoplethysmography with a High-Speed Camera Reveals Temporal and Amplitude Differences between Glabrous and Non-Glabrous Skin.

Photoplethysmography (PPG) is a noninvasive optical technology with applications including vital sign extraction and patient monitoring. However, its current use is primarily limited to heart rate and oxygenation monitoring. This study aims to demonstrate the utility of PPG for physiological investigations. In particular, we sought to demonstrate the utility of simultaneous data acquisition from several regions of tissue using remote/contactless PPG (rPPG). Specifically, using a high-speed scientific-grade camera, we collected rPPG from the hands (palmar/dorsal) of 22 healthy volunteers. Data collected through the red and green channels of the RGB CMOS sensor were analyzed. We found a statistically significant difference in the amplitude of the glabrous skin signal over the non-glabrous skin signal (1.41 ± 0.85 in the red channel and 2.27 ± 0.88 in the green channel). In addition, we found a statistically significant lead of the red channel over the green channel, which is consistent between glabrous (17.13 ± 10.69 ms) and non-glabrous (19.31 ± 12.66 ms) skin. We also found a statistically significant lead time (32.69 ± 55.26 ms in the red channel and 40.56 ± 26.97 ms in the green channel) of the glabrous PPG signal over the non-glabrous, which cannot be explained by bilateral variability. These results demonstrate the utility of rPPG imaging as a tool for fundamental physiological studies and can be used to inform the development of PPG-based devices.

Dermatophytoses Severity Score - A novel point-of-care scoring tool to assess the severity of dermatophytosis.

The rising prevalence of dermatophytosis in tropical countries coupled with drug resistance necessitates an objective scoring system to define the severity, monitor therapeutic response and predict prognoses. We attempted to establish and validate a new scoring system - Dermatophytoses Severity Score (DSS), for dermatophytoses affecting non-glabrous skin. A consensus group was convened to develop an objective and reproducible scoring system to describe the extent and severity of dermatophytosis of 200 consecutive patients with dermatophytosis. A second assessment entailed independent DSS scoring of the same patients by dermatologists and residents who were not part of the consensus group. The main outcome measured was index reliability, assessed in two steps, between the observers. A two-step assessment and DSS grading of 200 consecutive patients with clinically diagnosed dermatophytoses showed high reliability (Cronbach's α test and intraclass correlation coefficient). The DSS has demonstrated high reliability, and it could serve as a novel, reproducible and objective scoring tool for dermatophytosis.

Interdependency of Core Temperature and Glabrous Skin Blood Flow in Human Thermoregulation Function: A Pilot Study.

Human thermoregulation is governed by a complex, nonlinear feedback control system. The system consists of thermoreceptors, a controller, and effector mechanisms for heat exchange that coordinate to maintain a central core temperature. A principal route for heat flow between the core and the environment is via convective circulation of blood to arteriovenous anastomoses located in glabrous skin of the hands and feet. This paper presents new human experimental data for thermoregulatory control behavior along with a coupled, detailed control system model specific to the interdependent actions of core temperature and glabrous skin blood flow (GSBF) under defined transient environmental thermal stress. The model was tuned by a nonlinear least-squared curve fitting algorithm to optimally fit the experimental data. Transient GSBF in the model is influenced by core temperature, nonglabrous skin temperature, and the application of selective thermal stimulation. The core temperature in the model is influenced by integrated heat transfer across the nonglabrous body surface and GSBF. Thus, there is a strong cross-coupling between GSBF and core temperature in thermoregulatory function. Both variables include a projection term in the model based on the average rates of their change. Six subjects each completed two thermal protocols to generate data to which the common model was fit. The model coefficients were unique to each of the twelve data sets but produced an excellent agreement between the model and experimental data for the individual trials. The strong match between the model and data confirms the mathematical structure of the control algorithm.

Remote photoplethysmography with consumer smartphone reveals temporal differences between glabrous and nonglabrous skin: Pilot in vivo study.

Photoplethysmography (PPG) is a noninvasive optical technology, with applications including vital sign extraction and patient monitoring. The PPG acquisition skin type may be of importance. Skin is either nonglabrous (~90%) or glabrous (~10%). Clinical PPG collection is typically from glabrous (fingerpad), while proliferating wearables collecting PPG, which may perform critical functions like arrythmia detection, often acquire from atypical sites. Glabrous skin has significant differences from nonglabrous, including microcirculation, yet comparisons between their PPG signals have not been well reported. Using a smartphone-based remote/contactless PPG, a pilot dataset was collected from the hands (palmar/dorsal) of five healthy volunteers. The data shows statistically significant lead time (52 ± 36 ms) of glabrous over nonglabrous. Further, a trend of glabrous amplitude increase over nonglabrous (31%) was found. Although our study has a small number of participants, these results further the characterization of PPG skin differences, and can be used to inform development of PPG-based devices.

Offset analgesia is increased intra‐orally

Offset analgesia (OA) is commonly used to quantify endogenous pain inhibition. However, the potential role of afferent inputs and the subsequent peripheral factors from different body areas on the underlying mechanisms are still unclear. The aim of this cross-sectional study was to compare the magnitude of OA in four different body areas representing (a) glabrous and non-glabrous skin, (b) trigeminal and extra-trigeminal areas, and (c) intra- and extra-oral tissue. OA was assessed at the oral mucosa of the lower lip, the skin of the cheek, the forearm and the palm of the hand in 32 healthy and pain-free participants. OA testing included two trials: (1) a constant trial (30 s of constant heat stimulation at an individualised temperature of Pain50 [pain intensity of 50 out of 100]) and (2) an offset trial (10s of individualised Pain50 , followed by 5s at Pain50 + 1°C and 15 s at Pain50 ). Participants continuously rated their pain during each trial with a computerised visual analogue scale. A significant OA response was recorded at the oral mucosa (p < .001, d=1.24), the cheek (p < .001, d=0.84) and the forearm (p < .001, d=1.04), but not at the palm (p=.19, d=0.24). Significant differences were shown for OA recorded at the cheek versus the mucosa (p=.02), and between palm and mucosa (p=.007), but not between the remaining areas (p > .05). This study suggests that intra-oral endogenous pain inhibition assessed with OA is enhanced and supports the role of peripheral mechanisms contributing to the OA response.

Verrucous Carcinoma of the Foot: A Retrospective Study of 19 Cases and Analysis of Prognostic Factors Influencing Recurrence.

This study sought to evaluate a cohort of patients with verrucous carcinoma of the foot with special focus on 5 cases of locally recurrent tumors despite negative margins. Nineteen cases of verrucous carcinoma of the foot were identified through the University of Michigan (Ann Arbor, Michigan) pathology database from 1995 to 2019 and were included in demographic and clinical presentation analyses. Sixteen cases were treated at the University of Michigan and are included in the treatment analyses. A review of medical records was conducted to characterize clinical, surgical, and pathologic features. Recurrent cases were found to have a predilection for nonglabrous skin of the foot and great toe. Otherwise, there was little to differentiate outcomes between recurrent and nonrecurrent groups based on demographic, clinical, surgical, or histopathologic data. Recurrent tumors regrew locally and were not associated with histologic progression to conventional squamous cell carcinoma. Verrucous carcinoma of the nonglabrous surface of the foot should have a higher suspicion for possible local recurrence. Recurrence occurs within months of treatment, deserves early biopsy, and warrants aggressive re-treatment. Future directions should include greater examination of pathologic features and genetic markers to improve management of verrucous carcinoma of the foot.

Influence of uncomplicated, controlled hypertension on local heat-induced vasodilation in nonglabrous skin across the body.

The objective of this study was 1) to examine pooled effects of hypertension on nitric oxide (NO)-dependent vasodilation during local heating across multiple nonglabrous skin regions, and 2) explore regional differences. Responses were compared between 14 participants with uncomplicated hypertension controlled with medication (7 females, 61 ± 6 yr) and 14 age-matched nonhypertensive controls (6 females; 60 ± 5 yr). Cutaneous vascular conductance, normalized to maximum vasodilation (%CVCmax), was assessed at the upper chest, abdomen, dorsal forearm, thigh, and lateral calf during local heating. Across all regions, local skin temperatures were simultaneously increased from 33°C to 42°C (1°C·10 s-1) and held until a stable heating plateau was achieved (∼40 min), followed by continuous infusion of 20 mM of NG-nitro-l-arginine methyl ester (l-NAME; ∼40 min) at all sites until a stable l-NAME plateau was achieved. The difference between heating and l-NAME plateaus was defined as the NO-contribution. Statistical equivalence for each heating phase was determined based on equivalence bounds of ±10%CVCmax for between-group differences. Pooled (all-regions) %CVCmax responses were equivalent for baseline (two one-sided t tests; P < 0.001), heating plateau (P = 0.002), l-NAME plateau (P = 0.028), and NO-contribution (P = 0.003). For individual regions, responses were equivalent at baseline for the abdomen, thigh, and calf, the heating plateau for the thigh, and the l-NAME plateau for the calf (all P < 0.05). Conversely, the calf heating plateau was lower in the hypertension group (t test; P < 0.05). Local heat-induced cutaneous vasodilation was statistically equivalent between individuals with uncomplicated, controlled hypertension, and nonhypertensive age-matched adults when pooled across multiple skin sites. Conversely, individual between-region comparisons were generally too variable to permit definitive conclusions.

Effect of sensory blockade and rate of sensory stimulation on local heating induced axon reflex response in facial skin.

Local neuronal circuits in non-glabrous skin drive the initial increase of the biphasic cutaneous vasodilation response to fast non-noxious heating. Voltage-sensitive Na+ (NaV) channel inhibition blocks the afferent limb of the non-glabrous forearm cutaneous axon reflex. Slow local heating does not engage this response. These mechanisms have not been adequately investigated or extended into areas associated with flushing pathology. We hypothesized that despite regional differences in sensory afferents, both sensory blockade and slowing the heating rate would abate the cutaneous axon reflex-mediated vasodilator responses in facial skin. We measured skin blood flow responses (laser-Doppler flowmetry) of 6 healthy subjects (5 female) to non-noxious forearm, cheek, and forehead local heating, expressed as a percentage of cutaneous vascular conductance at plateau (CVC=flux/mean arterial pressure). We assessed CVC during fast (1°C/30s) and slow (1°C/10min) local heating to 43°C in both NaV inhibition (topical 2.5% lidocaine/prilocaine) and control conditions. NaV inhibition decreased forearm (control: 84±4, block: 34±9%plateau, p<0.001) and trended toward decreased forehead (control: 90±3, block: 68±3%plateau, p=0.057) initial CVC peaks but did not alter cheek responses (control: 90±3, block: 92±13%plateau, p=0.862) to fast heating. Slow heating eliminated the initial CVC peak incidence for all locations, and we observed similar results with combined slow heating and NaV inhibition. Slower sensory afferent activation rate eliminated the axon reflex response in facial and non-glabrous skin, but topical sensory blockade did not block axon reflex responses in flushing-prone cheek skin. Thus, slower heating protocols are needed to abate facial, particularly cheek, axon reflex responses.

A Novel Electrophysiological Sensor

Electrophysiological signals are electrical signals generated by different organs and tissues within the body like as brain, heart, muscles, etc.. These signals often contain information that can be utilized to access the physical and mental health status and therefore, have wide applications in medical and health care. [1] The non-invasive methods of measuring the electrical signal from brain, heart and muscles are known as electroencephalography (EEG), electrocardiography (ECG) and electromyography (EMG) respectively. Beyond medical applications electrophysiological recording has found various applications including human machine interface (HMI), mobile healthcare and internet of things (IoT). [2] Conventionally electrophysiological recording is performed using dry and wet gel electrodes. Besides being bulky and rigid wet gel electrodes are subject to drying by time and increasing skin-electrodes interface impedance, and dry electrodes are susceptible to motion artifacts because due to their slippage on skin during skin deformation. Therefore, their applications are limited to stationary and on-site medical care. Wearable, user-friendly sensors that can offer reliable signal recording during daily activities especially from hairy and microscopically rough skin such as scalp is an unaddressed problem. [3] Here we report a light weight, conductive polymer based, dry self-adhesive sensor (DSAS) for electrophysiological sensing from all-skin areas regardless of level of hair coverage and topology. DSAS contains of a low density array of funnel shaped structures (100/cm2). A single funnel shaped structure consist of a long stem (400-450 µm) and a micro-suction cup head (200-300 µm diameter) as it is shown in Figure 1.. The funnel shaped structures adhere to the skin when pressed against it due to pushing out the air and generating negative pressure inside the heads. Our theoretical studies suggest that one-centimeter square of DSAS can carry up to 2N force (200 gm). The long stem allows the adhesion of the DSAS to the hairy area as it can go between the hairs. The strong adhesion between the skin and sensor results firm and conformal contact to skin and reducing the skin-sensor interface impedance necessary for high signal to noise ratio signal recording. A novel low-cost and scalable fabrication method was developed for the fabrication of DSAS. To make electrically conductive polymer for the fabrication of DSAS a mixture of polydimethylsiloxane (PDMS) loaded with graphene and CNT at 3% of total weight (PDMS + CNT) is used for the fabrication of DSAS (Fig. 2 and 3). To achieve uniform distributions of CNTs within the polymer, an optimized dispersion process of CNT in PDMS was developed. It is found that exposure to an electric field yields CNT assembly into columnar structures parallel to the electric field (Fig. 4). A percolation threshold is observed at 3%, showing a dramatic increase from the neat polymer, and untreated polymer composite. The substrate is then molded into an array of funnel like micro-structure using a novel fabrication procedure, to allow self-adhesion to non-glabrous skin. The funnel shaped heads’ shell wall in the funnel like microstructure head is 15 µm thick which allows forming conformal contact to the rough surfaces such as skin and prevents leaking the air into the interface between sensor and surface.

Dermoscopy: A Review of the Structures That Facilitate Melanoma Detection.

Melanoma is currently the fifth most common cancer in the United States, resulting in more than 9000 deaths each year. Despite numerous improvements in the management of advanced melanoma, the cornerstone to ensuring a cure remains early detection. Both patient and physician awareness regarding the signs and symptoms of early melanoma remain paramount. As a result, much effort has been and continues to be expended in developing and refining effective diagnostic algorithms to help identify melanomas and differentiate them from nevi, such as the ABCDE rule (A for asymmetry, B for border irregularity, C for color variegation, D for diameter >6 mm, and E for evolution in lesion size, shape, or color). To assist in the detection of more subtle melanomas requires technology to augment a visual examination. Toward this end, a simple instrument called a dermatoscope has transformed not only the appreciation of the morphology of melanoma but also its growth dynamics. The discipline of dermoscopy has improved the detection of melanoma and other skin cancers, has resulted in the detection of thinner melanomas, and has helped improve the ability to differentiate nevi (benign lesions) from melanomas, which, in turn, has resulted in fewer biopsies of benign lesions. Since patients often first present to their primary care physicians for their health-related concerns, it is imperative that primary care physicians be able to recognize the lesions that are suspicious for melanoma. This review is intended to introduce osteopathic physicians to the dermoscopic features associated primarily with melanomas located on nonglabrous skin.

Are the antidepressive effects of massage therapy mediated by restoration of impaired interoceptive functioning? A novel hypothetical mechanism

Interoception is an individual person’s sense of the physiological condition of his/her entire body. Recent research has shown that depression is associated with impaired interoceptive accuracy. Treatments that can improve disturbed interoception are scarce in clinical practice and could complement established therapies. Accumulating evidence suggests that massage therapy significantly alleviates symptoms of depression. However, the mechanisms underlying these effects have remained unclear. We are going to propose a novel mechanism linking these antidepressive effects to a massage-induced modulation of interoceptive states. Particularly affective massage therapy applies slow, rhythmic, and caress-like touch that stimulates C tactile (CT) afferents in the non-glabrous skin. CT mediated touch elicits responses in interoceptive brain areas (e.g. the insular cortex) that have been associated with abnormal interoceptive representations in depressed subjects. Thus, we hypothesize that antidepressive effects of massage therapy are mediated by restoration of the impaired interoceptive functioning through stimulation of CT afferents or related interoceptive structures. If our proposed mechanism is valid, massage is probably one of the most ancient interoceptive treatments.

Thermogenic and psychogenic sweating in humans: Identifying eccrine glandular recruitment patterns from glabrous and non-glabrous skin surfaces.

In this experiment, psychogenic (mental arithmetic), thermogenic (mean body temperature elevation of 0.6 °C) and combined thermo-psychogenic treatments were used to explore eccrine sweat-gland recruitment from glabrous (volar hand and forehead) and non-glabrous skin surfaces (chest). It was hypothesised that each treatment would activate the same glands, and that glandular activity would be intermittent. Nine individuals participated in a single trial with normothermic and mildly hyperthermic phases. When normothermic, a 10-min arithmetical challenge was administered, during which sudomotor activity was recorded. Following passive heating and thermal clamping, sweating responses were again evaluated (10 min). A second arithmetical challenge (10 min) was administered during clamped hyperthermia, with its sudorific impact recorded. The activity of individual sweat glands was recorded at 60-s intervals, using precisely positioned, and uniformly applied, starch-iodide papers. Those imprints were digitised and analysed. Peak activity typically occurred during the thermo-psychogenic treatment, revealing physiologically active densities of 128 (volar hand), 165 (forehead) and 77 glands.cm-2 (chest). Except for the hand (46%), glands uniquely activated by one treatment were consistently <10% of the total glands identified. Glandular activations were most commonly of an intermittent nature, particularly during the thermogenic treatment. Accordingly, we accepted the hypothesis that psychogenic, thermogenic and thermo-psychogenic stimuli activate the same sweat glands in both the glabrous and non-glabrous regions. In addition, this investigation has provided detailed descriptions of the intermittent nature of sweat-gland activity, revealing that a consistent proportion of the physiologically active glands are recruited during these thermal and non-thermal stimuli.

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 ± 7 min and caused marked decreases at glabrous (42 ± 5%baseline, p < 0.001) and non-glabrous (69 ± 4%baseline, p < 0.001) skin. In glabrous skin, neural activity increased from 11 ± 1% at thermoneutral to 18 ± 1% (p < 0.001). In non-glabrous skin there was an initial decrease (p = 0.001) in neural activity from 13 ± 2% to 9 ± 1% (−0.2 °C decrease in Tre) and then increased (p = 0.002) to 21 ± 2% baseline at −0.5 °C Tre. Endothelial activity decreased in both glabrous (16 ± 3% to 6 ± 1%, p < 0.001) and non-glabrous (15 ± 1% to 7 ± 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.

T158. Sympathetic reinnervation in patient with transplanted upper limbs

Introduction Autonomic peripheral nerve reinnervation for skin vasculature and eccrine sweat glands has not been reported or analyzed before. As upper limb transplantation (ULT) remains an uncommon procedure sympathetic physiologic reinnervation process still remains a challenge and an important question to be answered in patients who undergo anastomosis of a peripheral nerve after a complete section. Methods A 52 year old male, underwent forearm transplantation 16 months after a high current electrical burn. Autonomic evaluation yearly during 4 years after transplant included: (1) evaluation of skin sympathetic response (SSR); (2) measurement of temperature with an infrared thermometer of high sensitivity (Nubee© range 50–350 °C, with one decimal point of discrimination); (3) evaluation of skin blood flow (SBF) with an infrared photopletysmograph; (4) capillary filling at the nails; (5) observation of the presence or absence of atrophic changes of the skin; (6) observation for the presence or absence of edema; (7) presence or absence of allodynia; (8) systolic blood pressure changes at the heart level and lowering the arm 60° (Portapres©); (9) presence or absence of the veno-arteriolar reflex Results SSR on both palmar surfaces was evident and reliable on the third year postransplantation. The patient clinically also referred sweating in both hands. No powder sweating was done Temperature of both hands had normal values, compared to the arms above transplant. No trophic changes were observed. The humidity of the skin appeared normal. There was no edema. No allodynia was present. The SBF demonstrated that the arteriolar vessels responded normally to stimuli such as breathing, baroreceptor stimulation, gravity pressor activation, and had normal blood pressure changes to breathing and lowering the arm. Capillary filling of the nail was normal. The veno-arteriolar reflex was present. Conclusion The eccrine sweat glands of the glabrous skin appear to be reinnervated as observed by the normal humidity, trophism of the hand, and presence of sympathetic skin response. The skin was not dry or scamous but soft and humid. The exocrine sweat glands of the non-glabrous skin of the forearm also had normal humidity and trophism which strongly suggests normal function of these glands. Piloerection could not be evaluated. The normal temperature, the absence of edema, the absence of trophic changes of the skin and more importantly the normal response of the SBF and SBP to deep breathing, postural changes and baroreceptor stimulation suggests that the arterial and venous system are reinnervated. The diffuse distributed sympathetic system seem to reinnervate skin and probably muscular vasculature after several years of a limb transplant.

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

BackgroundIschemia-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 methodsIn 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. ResultsIn 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). ConclusionsThe 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.

Chapter 11 - Skin vasoconstriction as a heat conservation thermoeffector

Cold exposure stimulates heat production and conservation to protect internal temperature. Heat conservation is brought about via reductions in skin blood flow. The focus, here, is an exploration of the mechanisms, particularly in humans, leading to that cutaneous vasoconstriction. Local skin cooling has several effects: (1) reduction of tonic nitric oxide formation by inhibiting nitric oxide synthase and element(s) downstream of the enzyme, which removes tonic vasodilator effects, yielding a relative vasoconstriction; (2) translocation of intracellular alpha-2c adrenoceptors to the vascular smooth-muscle cell membrane, enhancing adrenergic vasoconstriction; (3) increased norepinephrine release from vasoconstrictor nerves; and (4) cold-induced vasodilation, seen more clearly in anastomoses-rich glabrous skin. Cold-induced vasodilation occurs in nonglabrous skin when nitric oxide synthase or sympathetic function is blocked. Reflex responses to general body cooling complement these local effects. Sympathetic excitation leads to the increased release of norepinephrine and its cotransmitter neuropeptide Y, each of which contributes significantly to the vasoconstriction. The contributions of these two transmitters vary with aging, disease and, in women, reproductive hormone status. Interaction between local and reflex mechanisms is in part through effects on baseline and in part through removal of the inhibitory effects of nitric oxide on adrenergic vasoconstriction.