Measurement Of Skin Blood Flow Research Articles

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

Measurement of stress-induced sympathetic nervous activity using multi-wavelength PPG

The onset of stress triggers sympathetic arousal (SA), which causes detectable changes to physiological parameters such as heart rate, blood pressure, dilation of the pupils and sweat release. The objective quantification of SA has tremendous potential to prevent and manage psychological disorders. Photoplethysmography (PPG), a non-invasive method to measure skin blood flow changes, has been used to estimate SA indirectly. However, the impact of various wavelengths of the PPG signal has not been investigated for estimating SA. In this study, we explore the feasibility of using various statistical and nonlinear features derived from peak-to-peak (AC) values of PPG signals of different wavelengths (green, blue, infrared and red) to estimate stress-induced changes in SA and compare their performances. The impact of two physical stressors: and Hand Grip are studied on 32 healthy individuals. Linear (Mean, s.d.) and nonlinear (Katz, Petrosian, Higuchi, SampEn, TotalSampEn) features are extracted from the PPG signal’s AC amplitudes to identify the onset, continuation and recovery phases of those stressors. The results show that the nonlinear features are the most promising in detecting stress-induced sympathetic activity. TotalSampEn feature was capable of detecting stress-induced changes in SA for all wavelengths, whereas other features (Petrosian, AvgSampEn) are significant (AUC ≥ 0.8) only for IR and Red wavelengths. The outcomes of this study can be used to make device design decisions as well as develop stress detection algorithms.

Laser Speckle Contrast Imaging-based diagnosis of severe mesenteric traction syndrome: Hemodynamics and prostacyclin - A prospective cohort study.

Today, the diagnosis and grading of mesenteric traction syndrome relies on a subjective assessment of facial flushing. However, this method has several limitations. In this study, Laser Speckle Contrast Imaging and a predefined cut-off value are assessed and validated for the objective identification of severe mesenteric traction syndrome. Severe mesenteric traction syndrome (MTS) is associated with increased postoperative morbidity. The diagnosis is based on an assessment of the developed facial flushing. Today this is performed subjectively, as no objective method exists. One possible objective method is Laser Speckle Contrast Imaging (LSCI), which has been used to show significantly higher facial skin blood flow in patients developing severe MTS. Using these data, a cut-off value has been identified. This study aimed to validate our predefined LSCI cut-off value for identifying severe MTS. A prospective cohort study was performed on patients planned for open esophagectomy or pancreatic surgery from March 2021 to April 2022. All patients underwent continuous measurement of forehead skin blood flow using LSCI during the first hour of surgery. Using the predefined cut-off value, the severity of MTS was graded. In addition, blood samples for prostacyclin (PGI2) analysis and hemodynamics were collected at predefined time points to validate the cut-off value. Sixty patients were included in the study. Using our predefined LSCI cut-off value, 21 (35%) patients were identified as developing severe MTS. These patients were found to have higher concentrations of 6-Keto-PGFaα (p=0.002), lower SVR (p<0.001), lower MAP (p=0.004), and higher CO (p<0.001) 15min into surgery, as compared with patients not developing severe MTS. This study validated our LSCI cut-off value for the objective identification of severe MTS patients as this group developed increased concentrations of PGI2 and more pronounced hemodynamic alterations compared with patients not developing severe MTS.

Flowmotion imaging analysis of spatiotemporal variations in skin microcirculatory perfusion.

Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global and local regulation of the vessels and can be studied using frequency analysis of time-resolved blood flow signals. It has the potential to reveal clinically useful information about microvascular diseases, but the spatial heterogeneous nature of the microvasculature makes interpretation difficult. However, recent technological advances in multi-exposure laser speckle contrast imaging (MELSCI) enable new possibilities for simultaneously studying spatial and temporal variations in flowmotion. To develop a method for flowmotion analysis of MELSCI perfusion images. Furthermore, to investigate the spatial and temporal variations in flowmotion in forearm baseline skin perfusion. In four healthy subjects, forearm skin perfusion was imaged at 15.6 fps for 10 min in baseline. The time-trace signal in each pixel was analyzed using the wavelet transform and summarized in five physiologically relevant frequency intervals, resulting in images of flowmotion. Furthermore, a method for reducing the effect of motion artifacts in the flowmotion analysis was developed. The flowmotion images displayed patterns of high spatial heterogeneity that differed between the frequency intervals. The spatial variations in flowmotion, quantified as the coefficient of variation, was between 11 % and 31 % in four subjects. Furthermore, significant temporal variations in flowmotion were also observed, indicating the importance of a spatiotemporal analysis. The new imaging technique reveals significant spatial differences in flowmotion that cannot be obtained with single-point measurements. The results indicate that global statistics of flowmotion, such as the mean value in a large region of interest, is more representative of the microcirculation than data measured only in a single point. Therefore, imaging techniques have potential to increase the clinical usefulness of flowmotion analysis. • Flowmotion imaging displays significant spatiotemporal variations in forearm skin blood flow. • Flowmotion imaging has potential to be more accurate than single-point techniques. • A simple and effective method for motion artifact removal is presented.

Assessing the Association between Psoriasis and Cardiovascular Ischemia: An Investigation of Vascular Endothelial Growth Factor, Cutaneous Angiogenesis, and Arterial Stiffness.

Vascular endothelial growth factor (VEGF)-mediated angiogenesis's role in developing psoriasis and cardiovascular events has been established. However, the interplay between the two diseases regarding this cytokine remains an understudied area. This case-control study aimed to investigate the relationship between VEGF-mediated angiogenesis and cardiovascular ischemia in patients with psoriasis. The study included 200 clinically diagnosed treatment-naïve cases of psoriasis and 200 controls. The VEGF level, cutaneous vascularity, and cardiovascular ischemia were measured between cases and controls. Cutaneous vascularity was assessed using non-invasive imaging technique such as laser doppler imaging (LDI) and measuring skin blood flow measurement (SBFM). Cardiovascular ischemia was evaluated using noninvasive techniques by measuring carotid intima-media thickness (CIMT) and pulse-wave velocity (PWV). The arterial vasa vasorum was evaluated using ultrasound imaging. The study found a significant correlation between psoriasis severity and levels of VEGF (P < 0.001). Cases had significantly higher CIMT and PWV levels (P = 0.001 and <0.001, respectively). There was a significant positive correlation between the severity of psoriasis and the levels of cutaneous angiogenesis (r = 0.7, P < 0.001). According to this study, patients with psoriasis are at a higher risk of developing cardiovascular ischemia due to excessive angiogenesis associated with the condition. VEGF plays a key role in atheroma formation in psoriasis patients.

Exploring the relationship between capillary refill time, skin blood flow and microcirculatory reactivity during early resuscitation of patients with septic shock: a pilot study.

Capillary refill time (CRT), a costless and widely available tool, has emerged as a promising target to guide septic shock resuscitation. However, it has yet to gain universal acceptance due to its potential inter-observer variability. Standardization of CRT assessment may minimize this problem, but few studies have compared this approach with techniques that directly assess skin blood flow (SBF). Our objective was to determine if an abnormal CRT is associated with impaired SBF and microvascular reactivity in early septic shock patients. Twelve septic shock patients were subjected to multimodal perfusion and hemodynamic monitoring for 24h. Three time-points (0, 1, and 24h) were registered for each patient. SBF was measured by laser doppler. We performed a baseline SBF measurement and two microvascular reactivity tests: one with a thermal challenge at 44°C and other with a vascular occlusion test. Ten healthy volunteers were evaluated to obtain reference values. The patients (median age 70years) exhibited a 28-day mortality of 50%. Baseline CRT was 3.3 [2.7-7.3] seconds. In pooled data analysis, abnormal CRT presented a significantly lower SBF when compared to normal CRT [44 (13.3-80.3) vs 193.2 (99.4-285) APU, p = 0.0001]. CRT was strongly associated with SBF (R2 0.76, p < 0.0001). An abnormal CRT also was associated with impaired thermal challenge and vascular occlusion tests. Abnormal CRT values observed during early septic shock resuscitation are associated with impaired skin blood flow, and abnormal skin microvascular reactivity. Future studies should confirm these results.

Commentary: Multiple laser doppler flowmetry probes increase the reproducibility of skin blood flow measurements.

Commentary: Multiple laser doppler flowmetry probes increase the reproducibility of skin blood flow measurements.

Influence of Local Muscle Cooling on Mitochondrial-Related Gene Expression at Rest.

The purpose of this study was to determine the impact of localized cooling of the skeletal muscle during rest on mitochondrial related gene expression. Thermal wraps were applied to the vastus lateralis of each limb of 12 participants. One limb received a cold application (randomized) (COLD), while the other did not (RT). Wraps were removed at the 4 h time point and measurements of skin temperature, blood flow, and intramuscular temperature were taken prior to a muscle biopsy. RT-qPCR was used to measure expression of genes associated with mitochondrial development. Skin and muscle temperatures were lower in COLD than RT (p < 0.05). Femoral artery diameter was lower in COLD after 4 h (0.62 ± 0.05 cm, to 0.60 ± 0.05 cm, p = 0.018). Blood flow was not different in COLD compared to RT (259 ± 69 mL·min–1 vs. 275 ± 54 mL·min–1, p = 0.20). PGC-1α B and GABPA expression was higher in COLD relative to RT (1.57-fold, p = 0.037 and 1.34-fold, p = 0.006, respectively). There was no difference (p > 0.05) in the expression of PGC-1α, NT-PGC-1α, PGC-1α A, TFAM, ESRRα, NRF1, GABPA, VEGF, PINK1, PARK 2, or BNIP3-L. The impact of this small magnitude of difference in gene expression of PGC-1α B and GABPA without alterations in other genes are unknown. There appears to be only limited impact of local muscle cooling on the transcriptional response related to mitochondrial development.

Two Weeks Of Remote Ischemic Preconditioning Improved Cutaneous Microvascular Responses To Post-occlusive Reactive Hyperemia

PURPOSE: Repeated remote ischemic preconditioning (RIPC), induced by intermittent periods of ischemia and reperfusion in a limb body, improves non-nitric oxide (NO)-mediated endothelial-dependent cutaneous vasodilation. Post-occlusive reactive hyperemia (PORH) occurs following the release of a brief arterial occlusion and is principally mediated by non-NO mediated vasodilatory factors such as prostaglandins, sensory nerve axon reflex, and endothelium-derived hyperpolarizing factors (EDHFs). However, the role of repeated bouts of RIPC on the PORH response is unknown. The purpose of this study was to test whether two weeks of RIPC improves PORH elicited cutaneous microvascular hyperemia responses. METHODS: The study was conducted with twenty-one participants (Control; 24 ± 5 yr old, 4 M/4F, n = 8, RIPC; 22 ± 2 yr old, 7 M/6F, n = 13). The RIPC group received RIPC daily sessions over a two-week period (3 intervals of 4 days with RIPC followed by a 1 day break). Each RIPC session consisted of 4 repetitions of 5-minute arm blood flow occlusion interspersed by 5-minute reperfusion. PORH was elicited by brachial artery occlusion for 5 minutes by inflating an arm cuff to 200 mmHg, and the cutaneous hyperemic response was measured after cuff release. Skin blood flow measurements were collected with laser speckle contrast image (LSCI) before and after the repeated RIPC intervention. The control group did not receive RIPC but underwent repeated PORH measurements two weeks later. RESULTS: Both Time to Peak (Tp) and max/time improved after two weeks of RIPC (Tp; 16.5 ± 2.1 vs.15.2 ± 2.9 s, Pre vs. Post, p < 0.05, max/time; 0.11 ± 0.03 vs. 0.13 ± 0.04 CVC/s, Pre vs. Post, p < 0.05). The control group did not change after 2 weeks. CONCLUSIONS: These data suggest that non-NO mediated vasodilator responses in the skin microvasculature may be affected with 2 weeks of repeated RIPC.

Influence Of Local Muscle Cooling On Mitochondrial Related Gene Expression At Rest

Our lab has demonstrated physiological and molecular differences between exercising in ambient cold and an application of local cold. Local cold application has been shown to decrease the temperature of the skin and muscle, causing vasoconstriction, and decreasing blood flow. Currently, the effects of local cold application independent of exercise on mitochondrial related gene expression is unknown. PURPOSE: To determine the impact of localized cooling to the skeletal muscle during rest. METHODS: Thermal wraps were applied to the vastus lateralis (VL) of each limb of 12 participants. One limb received a cold application (randomized) in the form of circulated 10 °C fluid (COLD), while the other did not (CON). Wraps were removed at the 4-hour time point and measurements of skin temperature, blood flow, and intramuscular temperature were collected. Muscle biopsies were taken from the VL of each leg for later molecular analyses. Statistical significance (p < 0.05) was analyzed via paired t-tests. RESULTS: Skin temperature, measured via laser thermometer, was lower in COLD (34.84 ± 0.94 °C, to 13.15 ± 0.99 °C, p < 0.01). Similarly, thermal camera skin temperature measurements were (35.75 ± 0.94 °C, to 12.81 ± 0.93 °C, p < 0.01). Intramuscular temperature, via hypodermic thermocouple, also was lower in COLD (35.57 ± 0.76 °C, to 20.54 ± 1.31 °C, p < 0.01) after cold application. Blood flow, measured via ultrasound equipped with a transducer, did not change (0.64 ± 0.12 cm/sec, to 0.62 ± 0.17 cm/sec, p = 0.450). Arterial diameter was lower in COLD after 4 h (0.62 ± 0.05 mm, to 0.60 ± 0.05 mm, p = 0.018). Molecular outcomes (gene expression) will be measured soon via RT-qPCR and analyzed using the 2-∆∆ct method. CONCLUSIONS: Mitochondrial related gene expression data will help interpret previous local cold and exercise findings. Supported by NE-INBRE, NIGMS Funding (P20GM103427).

Multiple Laser Doppler Flowmetry Probes Increase the Reproducibility of Skin Blood Flow Measurements.

Cutaneous microcirculatory perfusion is commonly measured using laser Doppler flowmetry (LDF) probes, which provide a continuous, non-invasive quantification of skin blood flow (SkBF). However, inhomogeneities in the skin’s microvasculature density contribute to a decrease in reproducibility whenever an LDF probe is removed and replaced, as is the case during pre- and post-intervention or between-day measurements. Therefore, this study aimed to determine whether increasing the total number of individual LDF probes in a localized area improves the reproducibility of the measurement. Seven laser Doppler probes were secured in a custom-made acrylic holder designed to attach to the skin’s surface easily. SkBF, local skin temperature (Tsk), and blood pressure (BP) were assessed in 11 participants (6 M, 5 F, 42 ± 15 years). SkBF and Tsk were measured from the dorsal forearm (arm trial) for 5 min. Next, the multi-laser device was moved to the lateral side of the calf (leg trial), and measurements were obtained for 5 min. Each arm and leg trial was cyclically repeated three times, and all trials were separated by intermissions lasting 10–15 min. The average SkBF and the cutaneous vascular conductance (CVC) from all possible LDF probe combinations were not statistically different across the three arm and leg trials. Two-way mixed-effects models with absolute agreement were used to compute the intraclass correlation coefficient (ICC) for CVC, and the minimum ICC increased with the addition of LDF probes. The ICC of the average CVC from seven LDF probes was 0.96 between the arm trials and 0.91 between the leg trials, which suggests that there is excellent reliability and little difference between trials following the removal and replacement of the device. Moreover, all individual ICC values from ≥3 LDF probe combinations were greater than 0.70 (i.e., good reliability). These data suggest that SkBF measurements with multiple laser Doppler probes in a custom-made holder have excellent reproducibility after replacing the probes within the same participant. Therefore, this application could provide more reproducible assessments between repeated measurements (e.g., before and after exercise or clinical procedures) where the LDF probes must be removed and replaced within the same location.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser–Doppler flowmetry (LDF).Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non–invasive method for evaluation. With this method, it was aimed to examine the post–occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span.Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high–density lipoprotein, and low–density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise.Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

Spectral Changes in Skin Blood Flow Do Not Reflect Pressure Manipulations

Skin blood flow is commonly assessed by laser Doppler flowmetry. It has been suggested that pathophysiological conditions can be assessed by analysis of frequency domains of the laser Doppler signals. The frequency range of 0.06‐0.15 Hz has been associated with myogenic control of skin blood flow. We tested the hypothesis that changes in blood pressure would be detectable by short‐time Fourier transform of the myogenic portion of the laser Doppler signal. Laser Doppler sensors were placed on the right ventral forearm of fourteen healthy young volunteers (8 males, 6 females, age 30±6 years, mean ± SD) and a photoplethysmography sensor on the middle finger of the right arm. Measurements of skin blood flow were made with the right arm supported at heart level. Intravascular pressure of the forearm was manipulated by positioning the arm ~50˚ above the heart level to decrease pressure and lowering the arm ~50˚ below the heart level to increase pressure. Short‐time Fourier analyses were computed over the range 0.06 to 0.15 Hz. There were no statistically significant differences (p = 0.526) in spectral densities for baseline (5±7 x 10‐4dB, median ± SD), arm above heart (7±54 x 10‐4dB), and arm below heart (7±14 x 10‐4dB). The results demonstrate that spectral density in the myogenic frequency range is unchanged by manipulation of intravascular pressure. We conclude that spectral analysis of laser Doppler signals in the myogenic range does not reflect changes in blood pressure. These findings suggest that myogenic changes in the skin vasculature cannot be inferred from spectral analysis of laser Doppler signals.

Effect of Oral Contraceptive Phase on Mechanisms of Cutaneous Microvascular Function

While the effect of oral contraceptive (OC) use on endothelial function has been previously studied, precise mechanisms of endothelial function in this group of women remains unclear. The purpose of this study was to investigate the contribution of cyclooxygenase (COX), endothelial‐derived hyperpolarizing factors (EDHF), and nitric oxide (NO) to cutaneous microvascular function in women during the low hormone (LH) and high hormone (HH) phases of OC. Five young, healthy women taking monophasic, combined OC of any generation visited the lab twice: once during the LH (d 1‐2 of placebo pills) and once during the HH phase (d 3‐6+ of active pills). Participants were instrumented with three microdialysis fibers, and each site was randomized as control (lactated Ringer's), COX inhibition (10 mM ketorolac), or EDHF inhibition (50 mM tetraethylammonium, TEA). Laser‐Doppler flowmetry and local heaters were used to measure skin blood flow and induce local thermal hyperemia, respectively. Each site was heated from 33°C to 39°C at a rate of 0.1°C/sec. Once a plateau to local heating was established, 20 mM L‐NAME, a NO synthase inhibitor, was infused at each site to quantify NO‐dependent vasodilation. Maximal vasodilation was induced by heating the skin to 43°C and infusing 28 mM sodium nitroprusside. Data are mean ± SD. For baseline, there was a main effect of OC phase (p = 0.03) and treatment (p &lt; 0.001) but no interaction effect (p = 0.21) such that baseline was increased at COX‐inhibited sites (23 ± 3 %CVCmax) compared with control (14 ± 6 %CVCmax; p = 0.03) during the HH phase. For initial peak, there was a main effect of treatment (p &lt; 0.001) but no effect of OC phase (p = 0.99) or interaction effect (p = 0.59) such that initial peak was decreased at EDHF‐inhibited sites during the HH phase (17 ± 6 %CVCmax) compared with control (51 ± 23 %CVCmax; p = 0.02). For local heating plateau, there was a main effect of treatment (p &lt; 0.001) but no effect of OC phase (p = 0.28) or interaction effect (p = 0.21) such that plateau was decreased at EDHF‐inhibited sites during both phases (LH: 18 ± 12 %CVCmax; HH: 20 ± 9 %CVCmax) compared with respective control (LH: 63 ± 13 %CVCmax; HH: 67 ± 23 %CVCmax) and ketorolac sites (LH: 58 ± 21 %CVCmax; HH: 71 ± 12 %CVCmax; all comparisons: p &lt; 0.01). For %NO, there was no observed effect of OC phase (p = 0.77), treatment (p = 0.21), or interaction (p = 0.09). While not statistically significant, there was a large effect size for %NO between LH and HH phases at control sites (LH: 72 ± 15 %NO; HH: 50 ± 23 %NO; Cohen’s d = 1.05). During the LH phase, large effect sizes were observed between control and TEA (48 ± 14 %NO; d = 1.65) sites and control and ketorolac (54 ± 22 %NO; d = 0.96) sites. During the HH phase, a large effect size was observed between control and ketorolac (69 ± 17 %NO; d = 0.94) sites. These preliminary data suggest mechanisms underlying endothelial function vary across OC phase in women. While overall endothelial function (i.e., magnitude of local heating plateau) is similar between OC phases, there may be basal constriction (i.e., increased baseline with COX inhibition) and reduced NO‐dependent dilation during the HH phase. This shift in mechanisms underlying endothelial function in women using OC may contribute to cardiovascular health outcomes.

Which plantar region can predict peripheral arterial disease by using laser speckleflowgraphy?

Laser speckle flowgraphy (LSFG) is a new device that can measure skin blood flow and capture the movement of erythrocytes. However, there are a few reports on the use of LSFG to estimate skin blood flow, especially in the lower extremities. We aimed to compare plantar skin blood flow between patients with and without peripheral arterial disease (PAD) to discern the extent to which LSFG could accurately predict PAD. We prospectively measured the plantar skin blood flow in 28 patients with PAD and 37 participants without PAD at two hospitals from 2017 to 2021, using the ankle-brachial index (ABI) and LSFG. We partitioned the plantar into 12 parts: digits 1-5, medial metatarsal, middle metatarsal, lateral metatarsal, medial arch, middle arch, lateral arch, and heel, and compared the difference between the two groups and the area under the curve (AUC) of each point. Statistical analyses were performed to determine the sensitivity, specificity, false-positive rate, and false-negative rate at high accuracy points of AUC and ABI. There was a significant difference among the 12 points between the two groups, and the ratio using toe 1 and toe 5 was highly accurate. The ratio using toe 1 indicated higher sensitivity (89 vs. 82%), higher false-positive rate (22 vs. 4%), lower specificity (81 vs. 97%), and an equivalent false-negative rate (9 vs. 12%) to that of the ABI. These findings could facilitate the use of LSFG to estimate the skin blood flow condition in the plantar skin. Our results indicate that measuring toe 1 using LSFG could be used to somewhat assess PAD.

Assessing Light and Energy-Based Therapy by Optical Coherence Tomography and Reflectance Confocal Microscopy: A Randomized Trial of Photoaged Skin

Background and Objectives: Image-guided quantitative and semi-quantitative assessment of skin can potentially evaluate treatment efficacy. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are ideal for this purpose. This study assessed clinically relevant statistical changes in RCM and OCT features in photoaged skin after light and energy-based therapy. Methods: Novel statistical analyses were performed using OCT and RCM data collected during a previously published trial: a 12-week study of female décolleté skin randomized to four areas treated with thulium laser (L), photodynamic therapy (PDT), combined L-PDT, and control. Eight semi-quantitative RCM scores of photodamage and OCT measurements of skin roughness, blood flow, and epidermal thickness (ET) were evaluated and compared to dermoscopy and clinical skin scores. In statistical analysis, estimated treatment difference (ETD) was calculated. Results: Twelve women with moderate to severe photodamage were included. RCM and OCT data demonstrated a trend towards rejuvenation of epidermis with increased ET, changes in skin surface, and improved honeycomb pattern in RCM. In angiographic OCT, non-significant changes towards more regular capillary meshes were shown, which matched a decline in appearance of gross telangiectasias in dermoscopy. Improved skin tone after laser and L-PDT was identified in RCM, showing less edged papillae in 36% and 45%, and lentigo number declined in 55% of patients after treatments in dermoscopy. Based on clinical scores, L-PDT provided the greatest clinical improvement, which corresponded to superior ETD outcomes in ET and edged papillae shown in OCT and RCM, respectively. Conclusion: Objective OCT and RCM assessment of skin rejuvenation was demonstrated in this study. Importantly, image-based improvements corresponded to favorable clinical skin scores and fewer photoaging characteristics in dermoscopy. Importantly, most changes did not reach statistical significance, prompting further studies and emphasizing the modest value of non-randomized, non-blinded anti-aging trials.

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.

Heat Hyperemia or Reactive Hyperemia Alone Do Not Elicit Maximum Skin Blood Flow

The cutaneous circulation has been proposed as a model of generalized microvascular function which could be monitored noninvasively using laser doppler flowmetry. The response to heat hyperemia is commonly used to monitor disease or treatment related changes in microvascular function under the assumption that this represents maximum blood flow. We hypothesized that heat hyperemia alone does not elicit maximum skin blood flow. Purpose To understand how skin blood flow responds to heat hyperemia (HH), reactive hyperemia (RH), and a combination of both stimuli. Methods Ten healthy adults (30 ± 5 years; 74 ± 16.5 kg, mean ± SD) were subjected to 3 different conditions: reactive hyperemia (skin temp controlled at 33°C), heat hyperemia (skin heated to 42°C for 40 minutes), and HH + RH. Two Peltier-controlled thermomodules with laser doppler flow probes were placed on the right forearm to measure skin blood flow. A rapid release cuff on the right upper arm was inflated to 220 mmHg for 5 min to elicit RH while laser doppler flow (LDF) was monitored continuously from 1 min before cuff inflation (baseline) to 3 min after cuff release. This procedure was performed with skin temperature at 33°C and again after 40 min of local heating to 42°C. The mean of the two LDF probes was used in determining the highest 1-sec average skin blood flow for each condition. Beat-by-beat mean arterial pressure (MAP) was obtained by a photoplethysmographic sensor on the middle finger of the left hand. Cutaneous vascular conductance (CVC) was calculated as LDF / MAP. Results Both HH and RH increased LDF and CVC above baseline values (p<0.001). The highest 1-sec LDF and CVC averages were significantly higher during HH+RH when compared to RH or HH (*p < 0.001). Conclusion These results indicate that maximum blood flow and vasodilation are greater during combined heat and reactive hyperemia than during reactive hyperemia or heat hyperemia alone. Future studies should consider using a combination of HH and RH rather than HH alone to assess maximum cutaneous vasodilation.

Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect.

Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet. We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease. We measured transepidermal water loss and solute and water excretion in the urine. We quantified glomerular filtration rate (GFR) by intravital microscopy, and energy and nitrogen pathways by metabolomics. We measured skin blood flow and transepidermal water loss (TEWL) in conjunction with renal resistive indices and arterial blood pressure. Psoriatic animals lost large amounts of water across their defective cutaneous epithelial barrier. Metabolic adaptive water conservation included mobilization of nitrogen and energy from muscle to increase organic osmolyte production, solute-driven maximal anti-diuresis at normal GFR, increased metanephrine and angiotensin 2 levels, and cutaneous vasoconstriction to limit TEWL. Heat exposure led to cutaneous vasodilation and blood pressure normalization without parallel changes in renal resistive index, albeit at the expense of further increased TEWL. Severe cutaneous water loss predisposes psoriatic mice to lethal dehydration. In response to this dehydration stress, the mice activate aestivation-like water conservation motifs to maintain their body hydration status. The circulatory water conservation response explains their arterial hypertension. The nitrogen-dependency of the metabolic water conservation response explains their catabolic muscle wasting.