Increase In Cutaneous Blood Flow Research Articles

The Effect of Submaximal Exercise on Cutaneous Blood Flow, Thermoregulation and Recovery Hemodynamics Following Endurance Exercise

Aim. There are numerous reports of attenuation of cutaneous blood flow (CBF) during the recovery period after a single bout of exercise, but no one has investigated the CBF response to consecutive short-lasting aerobic exercise (SLAE) sessions following exhaustive endurance exercise (EEE) on daily basis, although this is a commonly used training regime in recreational athletes and could cause a cumulative increase in CBF that may be important for wound healing. This study examined the effects of EEE on forearm skin blood flow (LDF), cutaneous vascular conductance (CVC), and mean arterial pressure (MAP) in response to SLAE sessions performed for 7 days after EEE, as well as the correlation between cutaneous blood flow and indices associated with heart rate (HR) to examine the role of thermoregulation in post-exercise HR regulation. Methods. In 19 recreational runners, LDF, MAP, HR, heart rate recovery (HRR), and HR variability indices (lnRMSSD, lnHF, and lnLF/ HF) were measured after SLAE in the form of submaximal graded cycling performed on consecutive days after EEE in the form of a half marathon and compared with baseline values before EEE. A significant time effect was observed for all measured parameters throughout the study period. Results. Postexercise LDF increased 24 hours after EEE compared with baseline (77.814 AU compared with 54.712 AU). Postexercise hypotension was significantly more pronounced immediately after EEE compared with baseline (88.95.3 mmHg compared with 99.33.2 mmHg). However, postexercise CVC showed a progressive increase compared with baseline both immediately and 24 hours after EEE (0.53 0.07 AU/mmHg, 0.66 0.09 AU/mmHg compared with 0.4 0.09 AU/mmHg). A small negative correlation between LDF and HRR was observed throughout the experimental protocol. Conclusion. These results suggest that EEE strongly influences cutaneous and systemic hemodynamics and cardiac autonomic response during recovery after SLAE. Our most important finding was that EEE improved cutaneous perfusion 24 hours after completion of EEE, which may be important for wound healing. The results of our study are potentially applicable for patients with chronic wounds who should be encouraged to exercise moderately on daily basis and to include endurance exercises occasionally, as this strategy potentiates postexercise cutaneous perfusion.

Vascular endothelium as a target tissue for short-term exposure to low-frequency noise that increases cutaneous blood flow

Harmful health effects of exposure to low-frequency noise (LFN) defined as noise with frequencies at ≤100 Hz on the circulatory system have been a concern. However, there has been no study on the effects of exposure to LFN on the circulatory system with consideration of its frequencies and decibels. In this study, the effects of short-term exposure to broad-band LFNs and their pure-tone components (pure-tone LFNs) on cutaneous blood flow in the extremities including the hands were investigated. In our fieldwork study, we first sampled some kinds of common broad-band LFNs. Our human study then showed that broad-band LFN with a narrower frequency range more strongly increased cutaneous blood flow than did broad-band LFN with a wider frequency range. Pure-tone LFNs of 70–100 Hz at ≤85 dB(Z), but not pure-tone LFNs exceeding 100 Hz, further increased levels of cutaneous blood flow. Our wavelet-transform spectrum analysis of cutaneous blood flow next revealed that the nitric oxide (NO)-dependent and -independent vascular activities of the vascular endothelium were specifically increased by exposure to pure-tone LFN. Our animal study again indicated that exposure to pure-tone LFN increased cutaneous blood flow in mice with impairments of bilateral inner ears as well as cutaneous blood flow in control mice, suggesting a limited effect of inner ear function on the LFN-mediated increase in cutaneous blood flow. The NO-dependent suppressive effect of pure-tone LFN on cutaneous blood flow was confirmed by inhibition of vascular endothelial activity through intravenous injection of an NO inhibitor in wild-type mice. Taken together, the results of this study demonstrated that the vascular endothelium is a target tissue of LFN and that NO is an effector of the LFN-mediated increase in cutaneous blood flow. Since improvement of peripheral circulation could generally promote human health, short-term exposure to LFN may be beneficial for health.

Flujometría por láser Doppler como método de análisis para la evaluación de la mucositis oral inducida por quimioterapia: Un estudio piloto

Background: Oral mucositis (OM) is an inflammation of the oral mucosa due to cancer therapy that compromises the patient’s quality of life. Laser Doppler flowmetry (LDF) is a non-invasive method to monitor microvascular blood flow (BF) in real-time. Purpose: Develop a method to evaluate BF in the genian region cheek in patients undergoing chemotherapy by LDF and compare the degrees of OM and pain with evaluation of BF. Material and methods: Evaluation of OM was performed using the World Health Organization (WHO) and Oral Mucositis Assessment Scale (OMAS) scales and the visual analog scale for pain evaluation. For flowmetry analysis, a laser Doppler flowmeter (moorVMSTM™, 780 nm wavelength and VP3 probe), fixed by an acrylic resin support was used; VP3 probe was positioned on the genian region and the patient’s head was stabilized with a neck pillow for an accurate measurement. The Wilcoxon test was used to compare the flowmetry results at the studied times. The Pearson correlation coefficient was used to evaluate relationships between BF and the WHO, OMAS and visual analog scales. Results: Eleven patients of both sexes, aged between 30 and 78 years, with OM were included. An increase in cutaneous BF was observed at the initial times of OM, with progressive reduction during the chemotherapy cycle. There was a statistical difference (p<0.05) between time point T0 (first consultation) and time point T6 (last consultation). Conclusion: The method developed in this pilot study is effective, reliable, and reproducible, and allows the evaluation of BF dynamics in the genian region using LDF of patients undergoing chemotherapy at risk of developing OM.

Modulation of Blood Flow in the Skin of Human Legs during Transcutaneus Electrical Stimulation of the Spinal Cord

Changes in blood supply to the skin of the anterior-lateral surface of the shin of 12 healthy subjects were detected. The analysis was performed using laser Doppler flowmetry during transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz. The TSCS at T7 and L1 vertebrae level leads to a significant increase in cutaneous blood flow. With a stimulus intensity of 90% of the motor threshold, the increase in skin perfusion during stimulation at L1 was about 74%, and during stimulation at T7, 38%, relative to the baseline. We suggest that vasodilation and hyperemia of the skin during TSCS occur mainly due to the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important modulator that promotes vasodilation in TSCS. It is released by the nerve endings and the layer of endothelial cells. Inhibition of cystathionine-γ-lyase significantly reduces the increase in skin blood flow during TSCS. Therefore, it was concluded that H2S, as well as NO, is also involved in the vasodilation in the skin during TSCS.

Чрескожная электрическая стимуляция спинного мозга в двигательной реабилитации пациентов с травмой спинного мозга

It was previously demonstrated that the transcutaneous electrical spinal cord stimulation (TESCS) can be used to increase muscle strength, to initiate and improve voluntary movements in patients with chronic spinal cord injury (SCI). The paper focuses on the use of TESCS in motor rehabilitation of SCI patients. It presents the results of a single TESCS treatment in a representative sample 60 patients with SCI after a spinal injury at the upper cervical, cervicothoracic, thoracic, and lumbosacral levels. All patients had severe movement disorders, and many had SCI complications. The stimulation above the cervical and lumbar thickening of the spinal cord by single and rhythmic impulses resulted in motor reactions in 59 patients (movements of toes and / or fingers, contraction of leg muscles, etc.). Changes in spasticity, an increase in cutaneous blood flow, chronic pain decrease, and sensitivity improvement were also observed. 50 out of 60 patients underwent a course of motor rehabilitation with TESCS. A rehabilitation goal was defined for each patient (sitting without support, increased handgrip strength, moving from a wheelchair to a couch, etc.). Motor function improvements were recorded for all the patients, while 35 patients achieved the rehabilitation goal. The paper presents case reports of patients with different severity of movement disorders. The study includes records of the kinematics of movements demonstrating normalization of the sitting and standing posture after the course. As a result, the study has shown that the rehabilitation with TESCS facilitates the restoration of motor skills. The study has also revealed significant changes in visceral functions, which requires additional research.

Alteration of Pressure-Induced Vasodilation in Aging and Diabetes, a Neuro-Vascular Damage.

Skin is constantly subjected to pressure at different levels. Pressure-induced vasodilation (PIV) is one of the response mechanisms to low pressure that maintains the homeostasis of the skin. PIV results from the interaction of primary afferent nerves and vascular endothelium of skin vessels. Thanks to this cutaneous neuro-vascular interaction, the cutaneous blood flow increase allows the maintenance of an optimal level of oxygenation and minimizes the lack of vascularization of the skin tissue under low pressure. It seems to be associated with the cutaneous protection mechanisms to prevent pressure ulcers. In some contexts, where microangiopathy and neuropathy can occur, such as aging and diabetes, PIV is impaired, leading to a dramatic early decrease in local skin blood flow when low pressure is applied. In aging, PIV alteration is due to endothelial dysfunction, essentially from an alteration of the nitric oxide pathway. In the inflamm-aging context, oxidative stress increases leading to endothelial cell and nerve damages. An age-related sensory neuropathy will exacerbate the alteration of PIV during the aging process. In diabetes, non-controlled hyperglycaemia leads to an increase in several pathological biochemical pathways that involve oxidative stress and can affect PIV. Sorbinil, alagebrium and alpha-lipoic acid are able individually to restore PIV through a possible oxidative stress reduction. Candesartan, an angiotensin II type 1 receptor blocker, is also able to restore PIV and prevent pressure ulcer formation. The possibility of preventing pressure ulcer associated to diabetes and/or aging with the restoration of PIV seems to be a promising research path.

Mechanisms of blood flow regulation of in the skin during stimulation of the spinal cord in humans

Changes of the blood flow in the shin skin in the case of 12 healthy subjects by laser doppler flowmetry were observed under transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz were detected. It was found that the TSCS in the area of the vertebrae T11 and L1 leads to a significant increase in skin blood flow. With a stimulus intensity of 90% of the motor threshold, the microcirculation rate increased by more than 85% relative to baseline.The results of the study show that the stimulation of blood flow in the skin by TSCS is realized mainly due to the antidromic stimulation of sensory nerve fibers. An important mediator that contributes to vasodilation and increase of cutaneous blood flow in PSCS is nitric oxide (NO), which is predominantly endothelial in origin.

Low Stroke Volume during Exercise with Hot Skin Is Due to Elevated Heart Rate.

In the present study, HR was independently lowered by a low dose of β1-blockade (βB) to investigate its effect on SV during exercise when skin is hot. The effect of rapid skin cooling on reversing cardiovascular responses was also examined. Nine men cycled at 62% V˙O2peak wearing a water-perfused suit for 20 min during three conditions: (a) moderate Tsk (~33°C) (MOD), (b) hot Tsk (~38°C) (HOT), and (c) hot Tsk (38°C) with βB (HOT-βB). Skin temperature was then rapidly cooled at 20 min in all trials by cold water (0°C-2°C) perfusion while subjects continued cycling for another 20 min. When HR was lowered during HOT-βB (152 ± 4 bpm) to the same level as MOD (150 ± 4 bpm; P = 0.30), SV in HOT-βB (132 ± 8 mL) was also restored to the same level as MOD (129 ± 7 mL, P = 0.37) even with a significantly higher cutaneous blood flow (CBF) and lower mean arterial blood pressure. When Tsk was rapidly cooled, cardiac output, HR, and CBF significantly decreased while SV remained lower in HOT. Forearm venous volume was not different between trials during heating and cooling. The increase in HR rather than an increase in CBF or forearm venous volume was responsible for the decrease in SV during moderate-intensity exercise when Tsk was held at 38°C.

Mechanisms of Blood Flow Regulation in the Skin during Stimulation of the Spinal Cord in Humans

Changes in the blood flow in the shin skin were observed by laser Doppler flowmetry after transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz in 12 healthy subjects. It was found that TSCS in the area of the T11 and L1 vertebrae led to a significant increase in skin blood flow. The microcirculation rate increased by more than 85% relative to the baseline at a stimulus intensity of 90% of the motor threshold. Cutaneous blood flow activization by TSCS is implemented mainly through the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important mediator that contributes to vasodilation and increase in cutaneous blood flow upon TSCS. NO is predominantly of endothelial origin.

INFLUENCE OF TOPICALLY APPLIED MENTHOL COOLING GEL ON SOFT TISSUE THERMODYNAMICS AND ARTERIAL AND CUTANEOUS BLOOD FLOW AT REST

Topical application of menthol is a popular form of cold therapy and chemically triggers cold receptors and increases cutaneous blood flow. However, although cutaneous blood flow increases, it remains unknown where this increase arises from. Intramuscular temperature assessment may indirectly indicate a change in muscular blood flow. To establish intramuscular temperature, blood flow responses and subjective temperature sensation following application of menthol-based cooling gel to the anterior thigh. Controlled, randomized cross over interventional study. Twenty (age: 21.4 + 1.7) healthy males were treated on three separate days in random order with ice, a menthol-based gel or placebo gel (participant single blinded) on one anterior thigh. All measurements were taken at baseline and for 80 mins following treatment: 1) Skin, core, and intramuscular temperatures (1 & 3 cm deep); 2) femoral arterial blood flow (duplex ultrasound); 3) cutaneous blood flow (laser Doppler) and 4) subjective cold sensation. Ice and both gels decreased (p<0.0001, CI (Ice): -5.2 to -6.2 and CI (gels) -1.4 to -2.5) intramuscular temperature by 5.7 and 1.9 °C respectively, but by 80 mins were similar to each other (1.5-2 °C less than pre-treatment). Skin temperature mirrored muscle temperature with 8.8 and 4.2 °C respective decline for ice and gels. Menthol gel increased (p<0.0001) cutaneous blood flow by 0.3 ml/min compared to unaltered flow associated with the placebo gel and a decline of 0.3 ml/min for the ice. Menthol gel cold sensation was subjectively reported to be cooler (p<0.0001) than the other two treatments. Core temperature and arterial flow were unaffected. This is the first study to demonstrate the intramuscular cooling effect of menthol-based gel. However, the likely cause was from evaporative cooling despite menthol-derived increases in cutaneous blood flow and cooling sensation. Treatment, level 2.

Cardiovascular responses to exercise when increasing skin temperature with narrowing of the core-to-skin temperature gradient.

The decline in stroke volume (SV) during exercise in the heat has been attributed to either an increase in cutaneous blood flow (CBF) that reduces venous return or an increase in heart rate (HR) that reduces cardiac filling time. However, the evidence supporting each mechanism arises under experimental conditions with different skin temperatures (Tsk; e.g., ≥38°C vs. ≤36°C, respectively). We systematically studied cardiovascular responses to progressively increased Tsk (32°C-39°C) with narrowing of the core-to-skin gradient during moderate intensity exercise. Eight men cycled at 63 ± 1% peak oxygen consumption for 20-30 min. Tsk was manipulated by having subjects wear a water-perfused suit that covered most of the body and maintained Tsk that was significantly different between trials and averaged 32.4 ± 0.2, 35.5 ± 0.1, 37.5 ± 0.1, and 39.5 ± 0.1°C, respectively. The graded heating of Tsk ultimately produced a graded elevation of esophageal temperature (Tes) at the end of exercise. Incrementally increasing Tsk resulted in a graded increase in HR and a graded decrease in SV. CBF reached a similar average plateau value in all trials when Tes was above ~38°C, independent of Tsk. Tsk had no apparent effect on forearm venous volume (FVV). In conclusion, the CBF and FVV responses suggest no further pooling of blood in the skin when Tsk is increased from 32.4°C to 39.5°C. The decrease in SV during moderate intensity exercise when heating the skin to high levels appears related to an increase in HR and not an increase in CBF. NEW & NOTEWORTHY This study systematically investigated the effect of increasing skin temperature (Tsk) to high levels on cardiovascular responses during moderate intensity exercise. We conclude that the declines in stroke volume were related to the increases in heart rate but not the changes in cutaneous blood flow (CBF) and forearm venous volume (FVV) during moderate intensity exercise when Tsk increased from ~32°C to ~39°C. High Tsk (≥38°C) did not further elevate CBF and FVV compared with lower Tsk during moderate intensity exercise.

The Independent Effect of Heart Rate on Stroke Volume When Skin Temperature is Hot and Cool During Exercise

There are two hypotheses of how stroke volume (SV) is affected during hyperthermic exercise. The traditional hypothesis is that an increase in cutaneous blood flow (CBF) is thought to lead to a decline in SV. An alternate hypothesis is that a decline in SV is due to an increase in heart rate (HR). However, these two hypotheses have not been tested under the same thermal stress. PURPOSE: 1) To determine the independent effect of HR on SV by using low dose β 1-blockade (BB) when skin temperature (Tsk) is high (>38°C) during exercise. 2) To see how the rapid lowering of Tsk reverses the changes in cardiovascular variables. METHODS: Tsk was manipulated by wearing a water perfused suit that covered the whole body, except head, hands, and feet and maintained a perfused water temperature of 30 or 50°C. Subjects (n=8, active men 24 ± 4 y) cycled at 60% VO2peak for 20 min in three conditions: 30°C water with placebo (30-PL), 50°C water with PL (50-PL), and 50-BB. Tsk was rapidly cooled at 20 min of exercise in all trials by perfusing cold water through the suit (0°C) plus fans. Subjects continued to cycle for another 20 min with cool Tsk. Esophageal temperature (Tes), Tsk, VO2, cardiac output (CO), HR, mean arterial pressure (MAP), cutaneous blood flow (CBF), and forearm venous volume (FVV) were measured during exercise. RESULTS: Mean Tsk during the first 20 min of exercise were 33.4 ± 0.2, 38.1 ± 0.2, and 38.2 ± 0.2 °C, for 30-PL, 50-PL, and 50-BB, respectively. Mean Tsk during the last 20 min of exercise were 29.5 ± 0.2, 29.8 ± 0.3, and 30.0 ± 0.3 °C, for 30-PL, 50-PL, and 50-BB, respectively. When HR was lowered to the same level as 30-PL (147.9 ± 3.8 bpm) by BB in 50-BB (151.7 ± 4.0 bpm), SV was also restored to the same level as 30-PL (132.0 ± 7.3 ml) in 50-BB (135.6 ± 7.5 ml). SV was restored even with a significantly higher CBF (77.1 ± 3.4% vs 55.9 ± 3.6% for 50-BB vs 30-PL; p<0.05) and lower MAP (98.5 ± 2.6 mmHg vs 105.4 ± 3.3 mmHg for 50-BB vs 30-PL; p<0.05). When Tsk was rapidly cooled, HR and CBF were significantly decreased while SV was maintained in 50-PL. There was no apparent effect of Tsk on FVV responses. CONCLUSION: The increase in HR was responsible for the decrease in SV when Tsk was above 38°C. Rapidly cooling Tsk while Tes remains elevated decreased CBF and HR.

Effects of Multidirectional Vibrations Delivered in a Horizontal Position (Andullation®) on Blood Microcirculation in Laboratory Animals: A Preliminary Study.

BackgroundA whole-body vibration technique delivered in a horizontal position through a massage mattress was introduced in 2007. The present study analyzed the effects of different exposure periods to these vibrations on microcirculation of mice.Material/MethodsDifferent periods of vibrations (30Hz) were locally delivered in a horizontal position on the external abdominal skin in 3 randomized groups of mice (N=42). The 3 groups receiving vibrations were compared to an untreated control group (N=14). The 3 experimental groups received 3, 6, and 10 min of vibrations. The in vivo measurement of the arterial and venous diameters was done before and after each vibration period.ResultsAverage venous diameters (μm) after 6 to 10 min of vibrations were significantly increased (7% and 12%, p values 0.026 and 0.013, respectively), but 3 min did not significantly change average venous diameters. Arterial diameters (μm) did not significantly vary after 3, 6, and 10 min. In the control group, variations of arterial and venous diameters during 10 min were not significant.ConclusionsThis study shows a vasodilatory effect of low-frequency vibrations. The hypothesis of local cutaneous blood flow increase is retained. A phenomenon of shear stress of the endothelium induced by skin massage generates this local venous vasodilation and blood flow increase.

Increasing Skin Temperature During Exercise Lowers Stroke Volume Without Increasing Cutaneous Blood Flow.

Both skin (Tsk) and core temperature (Tc) are elevated in most studies of heat stress during exercise and this is accompanied by increased heart rate (HR) and decreased stroke volume (SV). However, only a few studies have systemically investigated the effect of progressively increasing Tsk on cardiovascular responses during exercise. PURPOSE:To systemically investigate how progressive increases in Tsk (32 to 40°C) affects cardiovascular responses and Tc during moderate exercise. METHODS: Subjects (n=8, active men 25±1 y) cycled at 60% VO2peak for 20-30 min. Tsk was manipulated by wearing a water perfused suit that covered the whole body, except head, hands, and feet and maintained a perfused water temperature of 20, 30, 40, and 50°C. Subjects performed all four trials separated by at least 72 h. Esophageal temperature (Tes), Tsk, VO2, Q, HR, mean arterial pressure (MAP), cutaneous blood flow (CBF), and forearm venous volume (FVV) were measured during exercise. RESULTS: Tsk was significantly different between all trials (P < 0.01) and averaged 32.4 ± 0.2, 35.5 ± 0.1, 37.5 ± 0.1, and 39.5°C ± 0.1°C, respectively. Tes was significantly different between each trial after 16 min of exercise (p < 0.05) and at the end of exercise were 37.6 ± 0.2, 38.3 ± 0.1, 39.2 ± 0.1, and 39.2 ± 0.2°C, respectively. The graded heating of Tsk resulted in a graded increase of HR and decrease of SV. However, CBF during exercise reached a similar average plateau value in all trials when Tes was above 38°C independent of Tsk. There was no apparent effect of Tsk on FVV, VO2, Q, and MAP. CONCLUSIONS: Graded increases of Tsk from 32 to 40°C progressively increased Tes and HR and decreased SV during moderate exercise. Tsk had no effect on CBF when Tes was above 38°C. High Tsk (39.5 ± 0.1°C) did not elicit higher CBF and FVV compared to low Tsk during moderate exercise. CBF and FVV responses suggest no further blood pooling in the forearm skin when Tsk is increased from 32.4 to 39.5°C. The decrease of SV during exercise when heating the skin is related to an increase of HR but not an increase in CBF.

Effect of continuous vs pulsed iontophoresis of treprostinil on skin blood flow

IntroductionSystemic sclerosis (SSc) is a rare disease affecting digital microcirculation, leading to finger ulcers and in some cases to amputation. Prostacyclin analogues can be used intravenously but their therapeutic effect is counterbalanced by potentially serious vasodilatation-induced side effects. Iontophoresis of treprostinil could be a promising local therapeutic alternative for SSc-related digital ulcers. Iontophoretic drug delivery is complex, and whether continuous or periodic current should be used remains debated. The objective of the present work is to compare the effect of continuous vs pulsed iontophoresis of treprostinil in rats. Materials and methodsTreprostinil (0.64mM and 0.064mM) and NaCl were delivered by cathodal iontophoresis onto the hindquarters of anaesthetized rats. Three protocols delivering the same quantity of current were compared: one was continuous (100μA during 20min) and two were periodic (B: twenty 1-min cycles with 200μA during 30s followed by 30s Off; and C: twenty 1-min cycles with 600μA during 10s followed by 50s Off) (n=8 for each protocol with each concentration). Skin blood flow was quantified using laser Doppler imaging and skin resistance was calculated with Ohm’s law. ResultsAll protocols induced a significant increase in skin blood flow. At the lower concentration (0.064mM treprostinil) the pulsed 10/50 sequence significantly enhanced cutaneous blood flow (Table 1; Fig. 1B) compared to continuous iontophoresis or the 30/30 sequence. We noted that the pulsed iontophoresis of NaCl (10/50 sequence) induced a significant early increase in cutaneous blood flow in comparison with continuous iontophoresis. Skin resistance measures were negatively correlated with current intensity delivered. ConclusionIn conclusion, pulsed iontophoresis of treprostinil with a 10s/50s (On/Off) protocol at 600μA increases the efficacy of iontophoresis at 0.064mM but not at a tenfold higher concentration. Pulsed iontophoresis could be used to optimize treprostinil iontophoresis, to provide similar efficacy with decreased costs, and should now be tested on humans.

The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus.

The use of glycine as a therapeutic option for improving sleep quality is a novel and safe approach. However, despite clinical evidence of its efficacy, the details of its mechanism remain poorly understood. In this study, we investigated the site of action and sleep-promoting mechanisms of glycine in rats. In acute sleep disturbance, oral administration of glycine-induced non-rapid eye movement (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core temperature. Oral and intracerebroventricular injection of glycine elevated cutaneous blood flow (CBF) at the plantar surface in a dose-dependent manner, resulting in heat loss. Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine inhibited the CBF increase caused by glycine injection into the brain. Induction of c-Fos expression was observed in the hypothalamic nuclei, including the medial preoptic area (MPO) and the suprachiasmatic nucleus (SCN) shell after glycine administration. Bilateral microinjection of glycine into the SCN elevated CBF in a dose-dependent manner, whereas no effect was observed when glycine was injected into the MPO and dorsal subparaventricular zone. In addition, microinjection of D-serine into the SCN also increased CBF, whereas these effects were blocked in the presence of L-701324. SCN ablation completely abolished the sleep-promoting and hypothermic effects of glycine. These data suggest that exogenous glycine promotes sleep via peripheral vasodilatation through the activation of NMDA receptors in the SCN shell.

Changes in biophysical properties of the skin following radiotherapy for breast cancer.

Acute radiation dermatitis is a common adverse effect in patients undergoing radiotherapy for breast cancer. However, the effects of radiotherapy on biophysical properties of the skin have rarely been investigated. In this prospective cohort study, we seek to determine the effects of radiotherapy for breast cancer on skin biophysical parameters. We measured various skin biophysical parameters (skin hydration, pH, sebum level, pigmentation, and blood flow) in 144 breast cancer patients by non-invasive techniques before and after radiotherapy. The measurements were simultaneously performed on the irradiated breast and the corresponding contralateral unirradiated breast for comparison. Following radiotherapy, the irradiated breast showed a significant decrease in skin hydration, increase in skin pH, increase in pigmentation, and increase in cutaneous blood flow. The contralateral unirradiated breast showed a slight increase in pigmentation but no significant changes in any of the other biophysical parameters after radiotherapy. No significant associations were found between patient characteristics (diabetes mellitus, hypertension, type of surgery, chemotherapy, hormone therapy) and changes in skin biophysical parameters following radiotherapy. In conclusion, radiation therapy for breast cancer induces measurable and significant changes in biophysical properties of the skin including hydration, pH, pigmentation, and blood flow. These findings give us a greater understanding of the effects of ionizing radiation on skin physiology, and provide non-invasive and objective methods to assess radiation dermatitis.

Anodal Iontophoresis of a Soluble Guanylate Cyclase Stimulator Induces a Sustained Increase in Skin Blood Flow in Rats

The treatment of systemic sclerosis-related digital ulcers is challenging. Although the only effective drugs are prostacyclin analogs, their use is limited by vasodilation-related adverse reactions. In this study, we assessed the local iontophoresis administration of three soluble guanylate cyclase (A-350619 [3-[2-[(4-chlorophenyl)thiophenyl]-N-[4-(dimethylamino)butyl]-2-propenamide hydrochloride], SIN-1 [amino-3-morpholinyl-1,2,3-oxadiazolium chloride], and CFM 1571 [3-[3-(dimethylamino)propoxy]-N-(4-methoxyphenyl)-1-(phenylmethyl)-1H-pyrazole-5-carboxamide hydrochloride]) and two nonprostanoid prostaglandin I2 (prostacyclin) receptor agonists (MRE-269 [[4-[(5,6-diphenylpyrazinyl)(1-methylethyl)amino]butoxy]-acetic acid] and BMY 45778 [[3-(4,5-diphenyl[2,4'-bioxazol]-5'-yl)phenoxy]acetic acid]) to induce vasodilation onto the hindquarters of anesthetized rats. Skin blood flow was quantified using laser Doppler imaging during the whole experience, and safety was assessed by continuous recording of blood pressure and histopathological examination. Anodal iontophoresis of A-350619 (7.54 mM) induced a sustained increase in cutaneous blood flow (P = 0.008 vs. control). All other drugs exhibited poor or no effect on skin blood flow. Vasodilation with A-350619 iontophoresis was concentration-dependent (7.5, 0.75, and 0.075 mM; P < 0.001, Jonckheere-Terpstra trend test), and repeated administrations do not suggest any risk of tolerance. This study also compared continuous versus intermittent iontophoresis protocols. Continuous anodal iontophoresis of A-350619 at 7.5 mM increases cutaneous blood flow with good local tolerance. Iontophoresis of soluble guanylate cyclase stimulators should be investigated as potential local therapy for digital ulceration in patients with scleroderma.

Cathodal Iontophoresis of Treprostinil Induces a Sustained Increase in Cutaneous Blood Flux in Healthy Volunteers

Prostacyclin analogues are the most effective drugs to treat sclerodermic digital ulcers, but their systemic use is limited by their frequent side effects. The authors tested whether the prostacyclin analogues treprostinil and iloprost, delivered by cutaneous iontophoresis, induce sustained vasodilatation. Twenty healthy volunteers received treprostinil by cathodal iontophoresis on the forearm. Skin blood flux was quantified using laser Doppler imaging. Treprostinil 250 µM induced an increase in cutaneous vascular conductance AUC(80) (min) (31 897 ± 24 390 %BL·min) compared with NaCl 0.9% (P < .005), treprostinil 2.5 µM (P < .005), and treprostinil 25 µM (P < .005). This was confirmed when flux was recorded for up to 10 hours. Systemic and skin tolerance of treprostinil were good. Iloprost was stopped early because of local toxicity. Treprostinil cathodal iontophoresis induces a sustained increase in cutaneous blood flow with good local tolerance. This could be investigated as a new local therapy for digital ulcers in scleroderma.

Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in resting heated humans

Hypocapnia attenuates the sweat response normally seen in hyperthermic resting subjects, but its effect on the blood flow response in their nonglabrous skin under the same hyperthermic conditions remains unclear. In the present study, we investigated whether hypocapnia induced by voluntary hyperventilation affects the blood flow response to heat stress in the nonglabrous skin of resting humans. Nine healthy male subjects were passively heated using legs-only hot water immersion and a water-perfused suit, which caused esophageal temperature (T(es)) to increase by as much as 1.0°C. During normothermia and at +0.6°C T(es) and +1.0°C T(es), the subjects performed two voluntary 7-min hyperventilation (minute ventilation = 40 l/min) trials (hypocapnic and eucapnic) in random order. End-tidal CO(2) pressure was reduced by 23-25 torr during hypocapnic hyperventilation, but it was maintained at the spontaneous breathing level during eucapnic hyperventilation. Cutaneous blood flow was evaluated as the cutaneous red blood cell flux in the forearm (CBF(forearm)) or forehead (CBF(forehead)) and was normalized to the normothermic spontaneous breathing value. Hypocapnic hyperventilation at +0.6°C T(es) was associated with significantly reduced CBF(forearm), compared with eucapnic hyperventilation, after 5-7 min of hyperventilation (395 to 429 vs. 487 to 525% baseline, P < 0.05). No significant difference in CBF(forehead) was seen during hypocapnic hyperventilation compared with eucapnic hyperventilation at +0.6°C T(es) or +1.0°C T(es). These results suggest that in resting humans, hypocapnia achieved through voluntary hyperventilation attenuates the increase in cutaneous blood flow elicited by moderate heat stress in the nonglabrous skin of the forearm, but not the forehead.