Skin Heating Research Articles

Revealing drug release and diffusion behavior in skin interstitial fluid by surface-enhanced Raman scattering microneedles.

Microneedle (MNs), as a novel dermal drug delivery formulation, have drawn a lot of attention in recent years. Drug release and diffusion behavior in dermal interstitial fluid (ISF) determines the pharmacokinetics and effectiveness of MNs, which have not been clearly elucidated until now. Herein, we develop surface-enhanced Raman scattering (SERS)-based detection MNs (D-MNs) for the sensitive analysis of model drugs in ISF. The surface of the D-MNs was deposited with a high density of hotspot-rich core-satellite gold nanoparticles, which would generate a sensitive SERS signal of a model drug (3,3'-diethylthiatricarbocyanine, DTTC) released by therapeutic MNs (T-MNs). Furthermore, the D-MNs produced an internal-standard signal for drug signal calibration, increasing the accuracy of detection. Taking advantage of the D-MNs, the release and diffusion behavior of the drug from T-MNs in the ISF of living mice was systematically studied. It was found that DTTC diffused without directional preference in ISF up to a distance of 1.5 cm. The intensities at diffusion sites decreased sharply with increasing distance from the release site (less than 0.3% at 1.5 cm). These results indicated that drug concentration gradient rather than ISF fluidity was a major driving force for the diffusion. Moreover, the application of water-soluble MN polymers, hydrophilic model drugs in T-MNs, as well as a heating or cupping treatment of mouse skin, enhanced drug diffusion in ISF. This work provides a new tool for in situ and real-time detection of molecules in ISF, which would be beneficial for the development and evaluation of MN-based therapeutic systems.

Automatic shoe drying oven integrated with Raspberry Pi Cloud system for advanced footwear industry

The drying oven functions to reduce the moisture content of raw materials until it reaches a certain moisture content to slow the rate of product damage due to biological and chemical activity. This research aims to design an automatic shoe-drying oven equipped with an LCD screen, exhaust fan, 8-level shelf, and electric heating temperature controller to provide maximum and even heating of leather shoes when gluing and drying leather shoes. Raspberry PI aims to combine and collect production process data in cloud storage in the form of a database, which will then be sent and displayed directly to the operator. The research methodology includes design, manufacturing, assembly, operational testing, performance testing, and evaluation stages. It can be concluded that the research results and progress reports include: (1) The design of the work system and mechanical system for the shoe drying oven can work well. (2) The Raspberry PI Cloud system can collect and display actual drying time data, (3) glue drying temperature of 60°C with a drying time of ±5 minutes, (4) skin heating temperature (texture creation) of 50°C-55°C requires warm-up time ±40 minutes, (5) This machine requires 850 watts of power.

Evaluation of the aerodynamic heating of the aircraft skin with taking into account ablation

The purpose of this work is to generalize the results of known studies and to form on their basis a simplified methodology for calculating the heating of the aircraft skin taking into account ablation, verification of the methodology based on experimental data.

Visualising and quantifying microvascular structure and function in patients with heart failure using optical coherence tomography.

Heart failure (HF) is characterised by abnormal conduit and resistance artery function in humans. Microvascular function in HF is less well characterised, due in part to the lack of tools to image these vessels in vivo. The skin microvasculature is a surrogate for systemic microvascular function and health and plays a key role in thermoregulation, which is dysfunctional in HF. We deployed a novel optical coherence tomography (OCT) technique to visualise and quantify microvascular structure and function in 10 subjects with HF and 10 age‐ and sex‐matched controls. OCT images were obtained from the ventral aspect of the forearm, at baseline (33°C) and after 30 min of localised skin heating. At rest, OCT‐derived microvascular density (20.3 ± 8.7%, P = 0.004), diameter (35.1 ± 6.0 μm, P = 0.006) and blood flow (82.9 ± 41.1 pl/s, P = 0.021) were significantly lower in HF than CON (27.2 ± 8.0%, 40.4 ± 5.8 μm, 110.8 ± 41.9 pl/s), whilst blood speed was not significantly lower (74.3 ± 11.0 μm/s vs. 81.3 ± 9.9 μm/s, P = 0.069). After local heating, the OCT‐based density, diameter, blood speed and blood flow of HF patients were similar (all P > 0.05) to CON. Although abnormalities exist at rest which may reflect microvascular disease status, patients with HF retain the capacity to dilate cutaneous microvessels in response to localised heat stress. This is a novel in vivo human observation of microvascular dysfunction in HF, illustrating the feasibility of OCT to directly visualise and quantify microvascular responses to physiological stimuli in vivo. Key points Microvessels in the skin are critical to human thermoregulation, which is compromised in participants with heart failure (HF).We have developed a powerful new non‐invasive optical coherence tomography (OCT)‐based approach for the study of microvascular structure and function in vivo.Our approach enabled us to observe and quantify abnormal resting microvascular function in participants with HF.Patients with HF were able to dilate skin microvessels in response to local heat stress, arguing against an underlying structural abnormality. This suggests that microvascular functional regulation is the primary abnormality in HF.OCT can be used to directly visualise and quantify microvascular responses to physiological stimuli in vivo.

Novel Method to Assess Endothelial Function via Monitoring of Perfusion Response to Local Heating by Imaging Photoplethysmography.

Endothelial dysfunction is one of the most important markers of the risk of cardiovascular complications. This study is aimed to demonstrate the feasibility of imaging photoplethysmography to assess microcirculation response to local heating in order to develop a novel technology for assessing endothelial function. As a measure of vasodilation, we used the relative dynamics of the pulsatile component of the photoplethysmographic waveform, which was assessed in a large area of the outer surface of the middle third of the subject’s forearm. The perfusion response was evaluated in six healthy volunteers during a test with local skin heating up to 40–42 °C and subsequent relaxation. The proposed method is featured by accurate control of the parameters affecting the microcirculation during the prolonged study. It was found that in response to local hyperthermia, a multiple increase in the pulsation component, which has a biphasic character, was observed. The amplitude of the first phase of the perfusion reaction depends on both the initial skin temperature and the difference between the basal and heating temperatures. The proposed method allows the assessment of a reproducible perfusion increase in response to hyperthermia developed due to humoral factors associated with the endothelium, thus allowing detection of its dysfunction.

Thermal Characteristics of Different Types of Cochlear Implants in Pediatric Cochlear Implant Users: AComparative Digital-Infrared Thermal Imaging Analysis.

Background:This study aimed to evaluate thermal characteristics of different types of pediatric cochlear implantsMethods:A total of 39 pediatric patients using Med-El (Synchrony®), Cochlear (Nucleus®), or Advanced Bionics (HiRes 90K®) type of cochlear implants were included. A digital infrared thermal imaging analysis was performed to measure the heating over the implant and the tissue heating of the skin below and around the device, while skin thickness and visual analog scale scores were also recorded.Results:Over the implant, heating values were significantly higher in the on-mode vs. off-mode of device for each type of implant (P ranged from <.05 to <.001). The implants groups were similar in terms of skin thickness, visual analog scale scores, on-mode values for heating over the implant, and the heating of the skin (below or around the device; <36°C for each), while the off-mode values for heating over the implant were significantly higher in the Med-El (Synchrony®) implants compared to other implants (median 31.75 vs. 31.30 and 30.20°C, P = .001). Skin thickness was negatively correlated with the heating over the implant (off-mode, r = −0.708, P < .001) and heating of the skin (around the device, r = −0.479, P = .028) in Advanced Bionics (HiRes 90K®) implants.Conclusion:Our findings emphasize that there is no hazard or discomfort from a cochlear implant in terms of heating of skin and no significant difference between 3 implant types in terms of skin thickness or tissue heating, whereas indicate the increased likelihood of thermal characteristics of implant to differ with respect to skin thickness in Advanced Bionics (HiRes 90K®) users.

Diagnostics and correction of microcirculation disorders and endothelial dysfunction in complex therapy of acute pancreatitis with antioxidant drugs

Objective. To assess the efficiency of using polypositional skin thermometry of high resolution with wavelet-analysis of the obtained curve as a screening noninvasive method for diagnostics and correction of microcirculatory disorders and endothelial dysfunction in complex therapy of acute pancreatitis using antioxidant drugs.&#x0D; Materials and methods. A prospective open randomized study of 30 patients with acute pancreatitis was carried out. The polypositional skin thermometry of high resolution with wavelet-analysis of the obtained curve was chosen as a screening method of diagnostics of microcirculatory disorders and endothelial dysfunction. Measurement of temperature oscillation amplitude with an accuracy to 0,001 С was performed in conditions of skin heating with index finger. The study was implemented before and after calf blood deproteinized hemoderivative infusion.&#x0D; Results. Reliable changes in skin temperature oscillation of the microcirculatory bed of the skin in the endothelial range on the days 1, 2 and 3 of drug infusion were detected. In the investigated group of patients, the phenomena of transitory organ dysfunction were arrested during 48 hours that proves the presence of pancreatitis of a moderate degree of severity. The temperature oscillation amplitudes of skin in neurogenic range significantly differed by the moment of arresting organ dysfunction.&#x0D; Conclusions. The method of polypositional skin thermometry of high resolution with wavelet-analysis of the obtained curve can be offered as an instrument for assessment of endothelial dysfunction prior to appearance of clinical manifestations of acute pancreatitis. The calf blood deproteinized hemoderivative infusions applied as a metabolic therapy positively influence the endothelial dysfunction in acute pancreatitis of a moderate degree of severity.

Numerical estimation of temperature response with step heating of a multi-layer skin under the generalized boundary condition

In this article, we discussed a one-dimensional bioheat transfer mathematical model that describes the process of temperature distribution in tissue for the multi-layer skin under the step heating generalized boundary condition. The finite difference scheme is used to estimate the temperature profile along with time and distance. We discussed the stability of the numerical scheme and also validated the accuracy of the numerical code by comparing the present results with the previous reference results. To remove heat from the skin is considered by the surface temperature, heat flux, and ambient temperature to be zero with the help of the unit step like function. Then, we observed that the skin temperature in the second kind boundary condition was slowly decreasing over time as compared to the first and third kind boundary conditions. The temperature or heat flux at the skin surface is assumed to be high then there is negligible effect of the blood perfusion rate on the temperature response over a short time period and the effect of blood perfusion rate is visible when the time duration is long. Effect of blood perfusion rate, heating and after removal of heating, water diffusion, and generalized boundary condition for the analysis of the behavior of temperature response in multi-layer skin are discussed in detail and the results obtained are presented graphically.

Periocular Skin Warming Promotes Sleep Onset Through Heat Dissipation From Distal Skin in Patients With Insomnia Disorder.

Study ObjectivesPeriocular skin warming before bedtime has been demonstrated to improve subjective sleep initiation in healthy adults with sleep difficulties scored six or higher in the Pittsburgh Sleep Questionnaire Index. This study aimed to investigate the effects of periocular skin warming on sleep initiation and thermoregulation processes in patients with insomnia disorder.MethodsParticipants included those with sleep difficulty (n = 22) and those with insomnia disorder (n = 16). Individuals from both groups were assessed at baseline (habitual sleep-wake schedule) and after two intervention conditions (use of a warming eye mask or a sham eye mask before habitual bedtime). The subjective and electroencephalographic sleep onset latency, along with proximal and distal skin temperature after periocular skin warming, were evaluated.ResultsPeriocular skin warming reduced objective sleep onset latency in independently of the group. Foot temperature and foot-proximal temperature gradient after getting into bed increased with periocular skin warming in independently of the group. However, the increase in hand temperature was observed only in the insomnia disorder group. Periocular skin warming also increased the normalized high frequency component of heart rate variability in independently of the group. The reduction of objective sleep onset latency was strongly associated with heat dissipation from the foot skin region.ConclusionThese results suggest that periocular skin warming promotes sleep initiation by enhancing heat dissipation from the distal skin regions in individuals with sleep difficulty and insomnia disorder. Periocular skin warming could thus be a novel non-pharmacological therapy for insomnia disorder.

Home‐Based Leg Heat Therapy Does Not Improve Vascular Function in Patients with Symptomatic Peripheral Artery Disease

INTRODUCTIONPatients with peripheral artery disease (PAD) suffer from severe exercise intolerance and accelerated rates of functional decline, resulting, in part, from significant endothelial cell dysfunction and the consequent impairment in leg blood flow. Unfortunately, few non‐invasive therapeutic interventions have been shown to ameliorate the microvascular dysfunction in patients with PAD. Repeated exposure to heat therapy (HT) improves endothelial function in sedentary young individuals, but the effects of this therapy on vascular function in patients with PAD remain poorly defined. The objective of the present study was to test the hypothesis that 8 weeks of home‐based leg HT would improve leg vascular function in patients with symptomatic PAD.METHODSThirty‐four patients with symptomatic PAD (66 ± 8 years, ankle‐brachial index: 0.68 ± 0.12) were randomized into one of two groups: home‐based leg HT (HT, n=18) or a control treatment (CON, n=16). Patients in both groups were provided with identical water‐circulating trousers and a portable heating pump and were asked to apply the therapy daily (7 days/week, 90 min per session) for 8 consecutive weeks. The pump issued to participants circulated water through the trousers at 43ºC in the HT group and 33ºC in the control group. Laser‐Doppler flowmetry was used to measure red blood cell flux, an index of skin blood flow, during local skin heating to 39°C for 40 min, followed by 43ºC for 20 min. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure and expressed as a percentage of maximal vasodilation (%CVCmax). Calf skeletal muscle perfusion was assessed using arterial spin labeling magnetic resonance imaging (MRI) following circulatory occlusion of the thigh for 5 min.RESULTSFive participants were either withdrawn prior to study completion or failed to complete the 8‐week follow‐up visit. The remaining 29 participants were included in the final analysis (CON: n=14, HT: n=15). Two participants from CON and 4 from HT were unable to undergo the MRI scans. At baseline, local skin heating to 39ºC increased %CVCmax to 55.8 ± 12.9% in CON and 52.5 ± 18.7% in the HT group. The change from baseline to 8 weeks in %CVCmax was similar between CON and HT (CON: ‐2.6 ± 13.9%, HT: ‐0.7 ± 16.3%, p=0.74). Peak calf blood flow during reactive hyperemia was comparable between groups at baseline (CON: 48.0 ± 24.6 ml/min/100g, HT: 43.8 ± 20.4 ml/min/100g, p=0.76). The change from baseline to 8 weeks in peak calf perfusion was also similar between CON and HT (CON: ‐4.8±21.9 ml/min/100g, HT: ‐2.8±11.0 ml/min/100g, p=0.84).CONCLUSIONEight weeks of home‐based leg HT does not improve leg vascular function in patients with symptomatic PAD.

Calcium‐activated Chloride Channel TMEM16A/ANO1 Does Not Mediate the Regulation of Sweating and Cutaneous Vasodilation in Humans In Vivo

The regulation of human body temperature during a heat stress is dependent on the activation of the heat loss responses of cutaneous vasodilation and eccrine sweating. While significant advancements have been made in our understanding of the mechanisms governing their regulation, new potential modifiers such as transmembrane member 16A (TMEM16A), a Ca2+‐activated Cl‐ channel also known as anoctamin 1 (ANO1), continue to be identified. In vitro and animal studies suggest a role for TMEM16A in the regulation of sweat secretion and vascular tone. For example, Ca2+ induced Cl‐current was abolished in TMEM16A deficit, but not BEST2 deficit, NCL‐SG3 human eccrine sweat gland cell lines. Further, animal models showed the activation of TMEM16A on vascular smooth muscle cells blunts vasodilation. However, direct evidence supporting a role of TMEM16 in mediating cutaneous vasodilation as well as eccrine sweating in humans in vivo remains to be established. Therefore, we evaluated the hypothesis that TMEM16A mediates the regulation of sweating and cutaneous vasodilation during a whole‐body heat stress in young adults.Twelve young (24 ± 2 years) adults (6 females) underwent a whole‐body heat stress induced by a water‐perfused suit to raise core temperature 1.1±0.1ºC above baseline resting levels. Sweat rate (ventilated capsule) and cutaneous vascular conductance (assessed as skin blood flow/mean arterial pressure and normalised to maximal conductance achieved via simultaneous local skin heating to 44°C and administration of sodium nitroprusside) were assessed at four skin sites on the forearm treated with 1) lactated Ringers (control), 2) 5 % dimethyl sulfoxide serving as a vehicle control, 3) 1 mM T16Ainh‐A01 (a TMEM16A blocker) or 4) 2 mM benzbromarone (another TMEM16A blocker). All drugs were administered continuously via intradermal microdialysis.Sweat rate increased as heating continued at all skin sites (P &lt; 0.001 for a main effect of heating stage). Neither the main effect of treatment site nor the interaction between treatment site and heating stage was significant (both P ≥ 0.318). Cutaneous vascular conductance increased in parallel to elevations in core temperature (P &lt; 0.001 for a main effect of heating stage). Although no main effect of treatment site was observed (P = 0.109), a significant interaction between heating stage and treatment site was measured (P &lt; 0.001). Post‐hoc analysis revealed that cutaneous vascular conductance at the DMSO‐treated site was higher than the control site at baseline (P = 0.047). By contrast, cutaneous vascular conductance at moderate elevations in core temperature (i.e., ≥0.4‐0.8 °C) was greater at the control site relative to the DMSO‐treated site (all P ≤ 0.013). Importantly, no differences were measured in cutaneous vascular conductance between the DMSO‐treated site and TMEM16A blocker‐treated sites (all P ≥ 0.073).Taken together, our findings demonstrate for the first time that TMEM16A does not contribute to the regulation of sweating and cutaneous vasodilation during whole‐body heating in young adults in vivo.

Visual display system of changes in physiological state for patients with chronic disorders

There is an acute issue of patients recovering with chronic disorders in medicine of critical conditions — they are a vegetative and minimally consciousness state. Such states develop in patients after coma and are characterized by the presence of wakefulness with complete or almost complete absence of signs of purposeful behavior. Capturing small reflexes and body signs allows observing changes in the physiological state of the patient, the effectiveness of the treatment course and requires a continuous process, which is not always possible considering to the high workload of medical staff. In this regard, visual display and data transmission systems for patients are more efficient. The display device should be safe, mobile and not restrict the patient’s movement, should not have a negative impact on the patient. The display method should be intuitively understandable and clear for prompt decision-making. The main parts of the visual system are sensors of physiological signs on the patient’s body, a control module, a visual display object, and a data transmission module. RGB Arlight 5060 LED strips with pixel addressing on a textile substrate are used as display elements. The object of the visual display consists of three layers: a duvet cover on the underside, a wool blanket, a cotton backing with LED strips. The paper presents an assessment of the heating of the proposed visual display system for patients with chronic disorders and a comparison of the results with the maximum permissible heating of human skin. The heating estimation was performed by COMSOL Multiphysics cross-platform finite element analysis, solver, and multiphysics simulation. The simulation results are compared with an experimental study using a contact temperature meter Centre 304 and an infrared camera Optris PI 640i. The security of the system has been confirmed. Scenarios for the indicators to reduce the thermal impact are proposed. The proposed visual display system may be relevant when monitoring the physiological state of patients in Intensive Care Units. The implementation of the system will help to see changes in the physiological state and increase the chances of getting out of a chronic condition in the future.

Transcutaneous and End-Tidal CO₂ Measurements in Hypoxia and Hyperoxia.

BACKGROUND: Transcutaneous measurement of carbon dioxide (CO₂) has been proposed for physiological monitoring of tactical jet aircrew because in some clinical settings it mirrors arterial CO₂ partial pressure (Paco₂). End-tidal monitoring in laboratory settings is known to give high-fidelity estimates of Paco₂.METHODS: The correspondence between end-tidal (PETco₂) and transcutaneous Pco₂ (tcPco₂) was examined in healthy volunteers under laboratory conditions of hyperoxia and hypoxia. Rest and exercise, skin heating and cooling, hyperventilation, and induced CO₂ retention were employed.RESULTS: Neither measure followed all known changes in Paco₂ and tcPco₂ changed when the skin temperature near the probe changed. Bland-Altman analysis showed significant nonzero slopes under most conditions. Regression analysis indicated that oxygen partial pressure (Po₂) in tissue measured as transcutaneous Po₂ (tcPo₂) is an important explanatory variable for tcPco₂ in addition to PETco₂, and that local skin temperature also has an effect. Additionally, absorption atelectasis from breathing 100% O₂ may cause PETco₂ to deviate from Paco₂.DISCUSSION: Even as a trend indicator for Paco₂, tcPco₂ is not useful under conditions that resemble those in the highly dynamic tactical jet aircraft environment. PETco₂ is also not a good indicator of CO₂ status in pilots who breathe nearly 100% O₂.Shykoff BE, Lee LR, Gallo M, Griswold CA. Transcutaneous and end-tidal CO₂ measurements in hypoxia and hyperoxia. Aerosp Med Hum Perform. 2021; 92(11):864-872.

Cutaneous microvascular vasodilatory consequences of acute consumption of a caffeinated soft drink sweetened with high-fructose corn syrup.

This study tested the hypotheses that compared to drinking water, consumption of a caffeinated soft drink sweetened with high‐fructose corn syrup (HFCS) attenuates the cutaneous vasodilatory response to local skin heating without (Protocol 1) and following ischemia‐reperfusion injury (Protocol 2). In a randomized, counterbalanced crossover design, 14 healthy adults (25 ± 3 year, 6 women) consumed 500 ml of water (water) or a caffeinated soft drink sweetened with HFCS (Mtn. Dew, DEW). Thirty minutes following beverage consumption local skin heating commenced on the right forearm (Protocol 1), while on the left forearm ischemia‐reperfusion commenced with 20 min of ischemia followed by 20 min of reperfusion and then local skin heating (Protocol 2). Local skin heating involved 40 min of heating to 39℃ followed by 20 min of heating to 44℃. Skin blood flow (SkBf, laser Doppler) data were normalized to mean arterial pressure and are presented as a cutaneous vascular conductance (CVC) and as percentage of the CVC response during heating to 44℃ (%CVCmax). Protocol 1: During local heating at 39℃, no differences were observed in CVC (water: 2.0 ± 0.6 PU/mmHg; DEW: 2.0 ± 0.8 PU/mmHg, p = 0.83) or %CVCmax (water: 59 ± 14%; DEW 60 ± 15%, p = 0.84) between trials. Protocol 2: During local skin heating at 39℃, no differences were observed in CVC (water: 1.7 ± 0.5 PU/mmHg; DEW: 1.5 ± 0.5 PU/mmHg, p = 0.33) or %CVCmax (water: 64 ± 15%; DEW 61 ± 15% p = 0.62) between trials. The cutaneous microvascular vasodilator response to local heating with or without prior ischemia‐reperfusion injury is not affected by acute consumption of a caffeinated soft drink sweetened with HFCS.

Na+-K+-ATPase plays a major role in mediating cutaneous thermal hyperemia achieved by local skin heating to 39°C.

Na+-K+-ATPase is integrally involved in mediating cutaneous vasodilation during an exercise-heat stress, which includes an interactive role with nitric oxide synthase (NOS). Here, we assessed if Na+-K+-ATPase also contributes to cutaneous thermal hyperemia induced by local skin heating, which is commonly used to assess cutaneous endothelium-dependent vasodilation. Furthermore, we assessed the extent to which NOS contributes to this response. Cutaneous vascular conductance (CVC) was measured continuously at four forearm skin sites in 11 young adults (4 women). After baseline measurement, local skin temperature was increased from 33°C to 39°C to induce cutaneous thermal hyperemia. Once a plateau in CVC was achieved, each skin site was continuously perfused via intradermal microdialysis with either: 1) lactated Ringer solution (control), 2) 6 mM ouabain, a Na+-K+-ATPase inhibitor, 3) 20 mM l-NAME, a NOS inhibitor, or 4) a combination of both. Relative to the control site, CVC during the plateau phase of cutaneous thermal hyperemia (∼50% max) was reduced by the lone inhibition of Na+-K+-ATPase (-19 ± 8% max, P = 0.038) and NOS (-32 ± 4% max, P < 0.001), as well as the combined inhibition of both (-37 ± 9% max, P < 0.001). The magnitude of reduction was similar between NOS inhibition alone and combined inhibition (P = 1.000). The administration of both Na+-K+-ATPase and NOS inhibitors fully abolished the plateau of CVC with values returning to preheating baseline values (P = 0.439). We show that Na+-K+-ATPase contributes to cutaneous thermal hyperemia during local skin heating to 39°C, and this response is partially mediated by NOS.NEW & NOTEWORTHY Cutaneous thermal hyperemia during local skin heating to 39°C, which is highly dependent on nitric oxide synthase (NOS), is frequently used to assess endothelium-dependent cutaneous vasodilation. We showed that Na+-K+-ATPase mediates the regulation of cutaneous thermal hyperemia partly via NOS-dependent mechanisms although a component of the Na+-K+-ATPase modulation of cutaneous thermal hyperemia is NOS independent. Thus, as with NOS, Na+-K+-ATPase may be important in the regulation of cutaneous endothelial vascular function.

ACUTE DIETARY NITRATE MAY IMPAIR CUTANEOUS VASCULAR CONDUCTANCE DURING LOCAL SKIN HEATING IN POSTMENOPAUSAL WOMEN

Declining estradiol production during menopause is linked to increased oxidative stress and reduced endothelial-dependent vasodilation. It is unknown whether supplementation with dietary nitrate may improve nitric oxide (NO) bioactivity and microvascular function in postmenopausal women. PURPOSE: To determine the effects of acute dietary nitrate ingestion on NO-mediated cutaneous vascular conductance (CVC) in a cohort of postmenopausal women. METHODS: In eight women (mean ± SD: age = 62 ± 4 y, BMI = 31 ± 2 kg/m2), two laser-Doppler flowmetry probes were affixed to the dorsal aspect of the forearm for measurement of red blood cell (RBC) flux during local skin heating to 39 °C and 44 °C. Assessments were made before and 3 h after ingesting 140 mL of beetroot juice containing 12.9 mmoL of inorganic nitrate. Fractional exhaled nitric oxide (FeNO) concentrations were measured at the same time points. Cutaneous vascular conductance (CVC) at 39 °C was calculated as RBC flux/ mean arterial pressure then normalized as a proportion of maximal CVC at 44°C. During the plateau phase at 39 °C, median spectral power of the endothelial NO-dependent frequency interval was analyzed using a Morlet wavelet transform. Pre-post comparisons were performed using within-sample t-tests. RESULTS: Following beetroot juice ingestion, FeNO concentrations (mean ± SD: 18 ± 8 ppb vs. 35 ± 16 ppb; p = 0.006, dz = 1.4) and spectral power of the NO-dependent frequency interval (0.01 - 0.02 Hz; p = 0.018, dz = 1.1) increased. Despite evidence for greater NO bioavailability, CVC at 39 °C was reduced (76 ± 12% vs. 50 ± 18%; p < 0.001, dz = 2.3). There was no change in maximal CVC at 44 °C (p = 0.287). CONCLUSION: A functional consequence of increased NO-bioavailability with acute dietary nitrate ingestion appears to be a diminished NO-mediated CVC response to local skin heating in our cohort of postmenopausal women with overweight and obesity. Future research should consider the effects of dietary nitrate coupled with an antioxidant supplement as means to further support NO-mediated endothelial function in such populations.

Perception of Thermal Comfort during Skin Cooling and Heating.

Due to the static and dynamic activity of the skin temperature sensors, the cutaneous thermal afferent information is dependent on the rate and direction of the temperature change, which would suggest different perceptions of temperature and of thermal comfort during skin heating and cooling. This hypothesis was tested in the present study. Subjects (N = 12; 6 females and 6 males) donned a water-perfused suit (WPS) in which the temperature was varied in a saw-tooth manner in the range from 27 to 42 °C. The rate of change of temperature of the water perfusing the suit (TWPS) was 1.2 °C min−1 during both the heating and cooling phases. The trial was repeated thrice, with subjects reporting their perception of the temperature and thermal comfort at each 3 °C change in TWPS. In addition, subjects were instructed to report when they perceived TWPS uncomfortably cool and warm during cooling and heating, respectively. Subjects reproducibly identified the boundaries of their Thermal Comfort Zone (TCZ), defined as the lower (Tlow) and upper (Thigh) temperatures at which subjects reported slight thermal discomfort. During the heating phase, Tlow and Thigh were 30.0 ± 1.5 °C and 35.1 ± 2.9 °C, respectively. During the cooling phase, the boundary temperatures of Tlow and Thigh were 35.4 ± 1.9 °C and 38.7 ± 2.3 °C, respectively. The direction of the change in the cutaneous temperature stimulus affects the boundaries of the TCZ, such that they are higher during cooling and lower during heating. These findings are explained on the basis of the neurophysiology of thermal perception. From an applied perspective, the most important observation of the present study was the strong correlation between the perception of thermal comfort and the behavioral regulation of thermal comfort. Although it is not surprising that the action of regulating thermal comfort is aligned with its perception, this link has not been proven for humans in previous studies. The results therefore provide a sound basis to consider ratings of thermal comfort as reflecting behavioral actions to achieve the sensation of thermal neutrality.

Regional variation in nitric oxide-dependent cutaneous vasodilatation during local heating in young adults.

What is the central question of this study? Are regional differences in nitric oxide (NO)-dependent cutaneous vasodilatation during local skin heating present in young adults? What is the main finding and its importance? NO-dependent cutaneous vasodilatation varied across the body. The abdomen demonstrated larger NO contributions, while the chest demonstrated smaller NO contributions, compared to other regions. This exploratory work is an important first step in characterizing regional heterogeneity of cutaneous microvascular control across the torso and limbs. Equally, it serves to generate hypotheses for future studies examining regional cutaneous microvascular control in ageing and disease. Regional variations in cutaneous vasodilatation during local skin heating exist across the body. While nitric oxide (NO) is a well-known modulator of this response, the extent of regional differences in NO-dependent cutaneous vasodilatation during local skin heating remains uncertain. In 16 habitually active young adults (8 females; 25±5years), cutaneous vascular conductance, normalized to maximum vasodilatation (% CVCmax ), was assessed at the upper chest, abdomen, dorsal forearm, thigh and lateral calf during local skin heating. Across all regions, local skin temperatures were simultaneously increased from 33 to 42°C (1°Cper 10s), and held until a stable heating plateau was achieved (∼40min). Next, with local skin temperature maintained at 42°C, 20mM of NG -nitro-l-arginine methyl ester (l-NAME) was continuously infused at each site until a stable l-NAME plateau was achieved (∼40min). The difference between heating and l-NAME plateaus was identified as the NO contribution for each region. There was no evidence for region-specific responses at baseline (P=0.561), the heating plateau (P=0.351) or l-NAME plateau (P=0.082), but there was for the NO contribution (P=0.048). Overall, point estimates for between-region differences in the NO contribution varied across the body from 0 to 19% CVCmax . The greatest effects were observed for the abdomen, wherein the NO contribution was consistently greater than for the other regions (range: 9-19% CVCmax ). The chest was consistently lower than the other regions (range: 7-19% CVCmax ). The smallest effects were observed between limb regions (range: 0-2% CVCmax ). These findings advance our understanding of the mechanisms influencing regional variations in the cutaneous vasodilator response to local skin heating in young adults.

Acute Consumption of a Caffeinated Soft Drink Sweetened with High Fructose Corn Syrup Does Not Modify the Cutaneous Microvascular Response to Ischemia‐Reperfusion Injury

Background Copious intake of soft drinks sweetened with high fructose corn syrup (HFCS) is associated with a heightened risk of cardiovascular disease, which is likely contributed to by chronic HFCS mediated endothelial dysfunction occurring secondary to decreased nitric oxide (NO) bioactivity. Acute consumption of a soft drink sweetened with HFCS does not affect cutaneous vasodilation during local heating, a functional test of NO bioactivity in the cutaneous microvasculature. However, this study was undertaken in the absence of a basal reduction in NO bioactivity, such as is speculated to occur with chronic intake of HFCS. Therefore, the present study tested the hypothesis that the cutaneous vasodilatory response to local skin heating following ischemia-reperfusion injury, which acutely reduces NO bioactivity, is attenuated following acute consumption of a caffeinated soft drink sweetened with HFCS compared to water. Methods In a randomized, counter-balanced crossover design, fourteen healthy young adults (six women) consumed 500 mL of either tap water (H2O) or a caffeinated soft drink sweetened with HFCS (Mtn. Dew®, DEW). 30 min following consumption, participants underwent 20 min of forearm ischemia and 20 min of reperfusion. Local skin heating at the forearm to 39⁰C was performed for 40 min and increased to 44⁰C for 20 min. Skin blood flow (SkBF) was measured on the dorsal forearm using laser Doppler flowmetry, blood pressure was measured using the Penaz method, and heart rate was measured via 3-lead electrocardiogram. Cutaneous vascular conductance (CVC) was calculated as the quotient of SkBF and mean arterial pressure (MAP). SkBF and CVC data during local heating to 39⁰C, which is mostly a NO mediated response, were normalized as a percentage of maximal values obtained during local skin heating to 44⁰C. Data are presented as mean ± SD. Results During local skin heating at 44⁰C, there were no differences observed between H20 and DEW trials for SkBF (H2O: 252 ± 37 PU; DEW: 240 ± 35 PU, p = 0.317), CVC (H2O: 2.6 ± 0.4 PU/mmHg; DEW: 2.4 ± 0.5 PU/mmHg, p =0.215), MAP (H2O: 96 ± 6 mmHg; DEW: 101 ± 10 mmHg, p = 0 .162), and heart rate (H2O: 59 ± 7 bpm; DEW 60 ± 10 bpm, p = 0.654). During local skin heating to 39°C, no differences were observed in absolute SkBF (H2O: 154 ± 44 PU; DEW: 152 ± 44 PU, p = 0.879), percent of maximal SkBF (H20: 60.6 ± 12.2%; DEW 62.4 ± 12.7% p = 0.272), absolute CVC (H2O: 2 ± 0.5 PU/mmHg; DEW: 1.5 ± 0.5 PU/mmHg, p = 0.368), or percent of maximal CVC (H2O): 63.8 ± 13.9%; DEW 62.6 ± 13.7% p = 0.787) in the DEW and H2O trials. However, during local heating at 39°C DEW did result in a higher MAP (H2O: 92 ± 7 mmHg; DEW: 100 ± 12 mmHg, p = 0.022) and heart rate (H2O: 56 ± 7 bpm; DEW 59 ± 8 bpm, p = 0.032) compared to H2O. Conclusion Under conditions of ischemia-reperfusion injury, these data indicate that, compared to an equivalent volume of water, consumption of 500 mL of a caffeinated soft drink sweetened with HFCS does not affect the cutaneous vasodilatory response to local heating, a mostly nitric oxide mediated response.

Regional cutaneous vasodilator responses to rapid and gradual local heating in young adults.

To examine the extent of regional variations in cutaneous vasodilatation during rapid and gradual local thermal hyperaemia (LTH) in young adults. In thirty young adults (21±3 years, 15 females), cutaneous vascular conductance, normalized to maximum local skin heating at 44°C (%CVCmax), was assessed at the upper chest, abdomen, dorsal arm, dorsal forearm, thigh, and medial calf during rapid (33-42°C at 1°C·20 s-1) and gradual (33-42°C at 1°C·5 min-1) LTH on separate days. For both protocols, local temperatures were held at 42°C for up to 35min, followed by 20-30min at 44°C. During rapid LTH, between-region responses were evaluated at baseline, the initial vasodilator peak, and 42°C plateau. During gradual LTH, responses were assessed at baseline and the 42°C plateau. There were significant main effects of body region on %CVCmax for the initial peak and plateau during rapid LTH and for the plateau during gradual LTH (all P<0.001) Conversely, main effects of sex and the sex by region interaction were not significant (all P>0.05). The magnitudes of between-region differences varied across the body (~1-17% range). The greatest effects were observed for the abdomen, wherein responses were consistently lower compared to other regions. Further, responses were consistent between males and females across all body regions and heating phases. Regional variations in the cutaneous vasodilator response to local heating are evident for rapid and gradual LTH in young adults, with the largest effects observed for the abdomen, albeit regional differences were similar between sexes.