Measurement Of Skin Blood Flow Research Articles

Nonlinear dynamics of skin blood flow response to mechanical and thermal stresses in the plantar foot of diabetics with peripheral neuropathy.

Diabetic foot ulcers (DFU) are a major complication in diabetics. Impaired microvascular reactivity is a major contributor to the development of DFU and has been traditionally quantified by time-domain or frequency-domain measures of skin blood flow (SBF). These measures, however, are unable to characterize the changes of nonlinear dynamics of SBF associated with diabetes and peripheral neuropathy. The objective of this study was to investigate altered nonlinear dynamics of skin blood flow in the plantar foot of diabetics with peripheral neuropathy. 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls were recruited. SBF at the first metatarsal head in response to a loading pressure of 300 mmHg and a local heating was measured using laser Doppler flowmetry. A sample entropy approach was used to quantify the degree of regularity of SBF. Our results showed that the regularity degree of SBF in the diabetic foot underwent only small changes during post-occlusive reactive hyperemia and thermally induced biphasic response compared to non-diabetics. SBF of the diabetic foot has higher degree of irregularity during reactive hyperemia because of attenuated myogenic activity, and demonstrated higher regularity during the biphasic response largely due to significantly enhanced cardiac activities. This study suggests that the regularity degree of SBF at the first metatarsal head could be used to assess impaired microvascular reactivity and thus may be used to assess the risk for DFU in diabetics with peripheralneuropathy.

Evaluation of skin perfusion pressure to assess refractory foot ulcers.

The number of patients with foot gangrene caused by critical ischaemia and severe infection is increasing significantly in developed countries. The measurement of perilesional skin blood flow by skin perfusion pressure (SPP) is useful to select the appropriate treatment of gangrenous lesions, in that it is not affected by calcifications of blood vessels. However, the prognosis of a foot ulcer may also be affected by the level of blood sugar and infections. This study aimed to validate the use of SPP in cases of foot gangrene and ulcers in patients with and without diabetes mellitus (DM) and infection. Clinical symptoms, ankle-brachial pressure index (ABPI) and SPP were assessed to evaluate the condition of each foot ulcer. Every foot ulcer was treated as independent, even if a participant had multiple ulcers. All ulcers for which we measured SPP were subject to the analysis. All ulcers were purely ischaemic in nature and were exclusively located on the foot or toes. Data were collected from 117 foot ulcers on 91 toes and feet from 65 patients. Almost all SPP values in healed cases were > 27 mmHg. There were three patients whose ulcers failed to heal by conservative treatments were complicated with severe infection. However, no effect of DM on the relationship between SPP values and prognosis was observed. Logistic regression analysis of all ulcers except for the 5 cases complicated with infection revealed that those with 30 mmHg or lower SPP values are likely to heal by conservative treatment with 23% or lower probability, whereas any ulcer with more than 50 mmHg SPP value and without severe infection may heal without the need for further operations with 80% or higher probability. The combination of SPP and careful evaluation of infection may be a good parameter to decide the appropriate treatment for ischaemic skin ulcers, regardless of the complication of DM.

Oscillatory pattern of acral skin blood flow within thermoneutral zone in healthy humans

The acral skin contains arteriovenous anastomoses, which probably is the main part of skin microcirculation for blood flow adjustments and thermoregulation in the thermoneutral zone. The objective was to investigate if an increase in sympathetic activation during cooling influences the oscillatory pattern of acral skin blood flow.We had measurements of bilateral acral skin blood flow (n = 12) during lowering of ambient temperature from 32 °C to 18 °C. We quantified the oscillatory pattern as the time averaged wavelet spectral powers, coherence and phase angles in three frequency intervals (0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz). The differences were tested by Wilcoxon signed rank sum method between adjacent intervals.The absolute fluctuations in laser Doppler flux at 0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz were similar at 32 °C and 25 °C, and decreased at 18 °C (p < 0.001). The relative fluctuations (amplitude of the fluctuations relative to median flux value) in laser Doppler flux at 0.01–0.02 Hz, 0.02–0.05 Hz and 0.05–0.08 Hz were higher at 25 °C and 18 °C as compared to 32 °C (p < 0.002). The coherence between the oscillations of signals from right and left finger tips was highest (median coherence > 0.89) at 25 °C, and lower at 32 °C and at 18 °C.The median phase angles between the flux signals from right and left finger tips were close to 0 radians.We found that the relative fluctuations in acral skin blood flow increased during vasoconstriction due to cooling. Wavelet analysis of acral skin blood flow oscillations could serve as a future clinical tool.

Attenuated Sweating Responses in Tattooed Skin During a Passive Whole‐body Heat Stress

Tattoos have increased in popularity in the last 10–15 years among individuals between the ages of 18–40, with a high prevalence in athletes and members of the military. The tattooing process involves repeated needle insertions (50 to 3,000 times per minute) to permanently deposit ink at a depth of 3–5 mm into the dermal layer, potentially damaging and impairing thermoregulatory mechanisms (i.e., eccrine sweat glands and cutaneous vasculature). The aim of the present study was to test the hypothesis that reflex increases in sweat rate (SR) and cutaneous vasodilation are blunted in tattooed skin (TAT) compared to adjacent healthy skin (CON) during a passive whole‐body heat stress (WBH). Four individuals (2M, 2F) with a substantial area of tattooed skin participated in the study. Skin blood flow (laser‐Doppler flowmetry; LDF) and SR (capacitance hygrometry) were continuously measured during normothermic baseline (34 °C water perfusing a tube‐lined suit) and WBH (increased core temperature 1.0 °C via 48 °C water perfusing the suit). LDF and SR were assessed in areas not exposed to direct heating. Cutaneous vascular conductance (%CVCmax) was calculated from the ratio of LDF to mean arterial pressure and normalized to maximal responses obtained by local heating at 42 °C following WBH. Results indicated that the laser‐Doppler measurement technique is clearly affected by tattooing not allowing for an accurate measurement of skin blood flow in TAT. The accumulated sweating responses throughout the duration of WBH (area under the curve) were attenuated in TAT relative to CON (TAT: 19.06 ± 13.20 vs CON: 24.34 ± 15.61 mg/cm2, p=0.04). The attenuated thermoregulatory reflex increases in SR in TAT could be due to the accumulation of ink within the dermal layer, damage to the sweat gland from repeated needle insertions, or some combination therein. Further research is warranted to assess whether attenuated sweating responses in tattooed skin translate to increased risk of heat‐related injury especially when tattooing covers a higher percentage of body surface area.

Significance of Skin Blood Flow Measurement Using Laser Speckle Contrast Imaging for Two-dimensional Blood Flow Mapping

Significance of Skin Blood Flow Measurement Using Laser Speckle Contrast Imaging for Two-dimensional Blood Flow Mapping

PP.12.06] PENILE MICROVASCULAR ENDOTHELIAL FUNCTION IN HYPERTENSIVE PATIENTS

Objective: The primary aim of this study was to test penile endothelial microvascular function in patients with treated arterial hypertension, compared to an age-matched group of normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we tested the acute penile microvascular effects induced by the oral administration of the phosphodiesterase type 5 inhibitor sildenafil citrate (SIL). Design and method: Endothelium-dependent penile microvascular reactivity of hypertensive patients (aged 58.8 ± 6.6 years, n = 34) and age-matched healthy volunteers (n = 33) was evaluated at rest and 60 minutes following oral administration of SIL (100 mg). LSCI was coupled with the cutaneous iontophoresis of acetylcholine (ACh) using increasing anodal currents. The measurements of skin blood flow (arbitrary perfusion units, APU) were divided by values of mean arterial pressure to give the cutaneous vascular conductance (CVC) in APU/mmHg. Results: Office systolic arterial pressure was 122.6 ± 8.8 and 136.7 ± 13.8 mmHg for control and hypertensive subjects, respectively (P < 0.0001); diastolic arterial pressure was 79.3 ± 6.6 and 86.7 ± 7.6 mmHg for control and hypertensive subjects, respectively (P < 0.0001). The basal values of skin microvascular flow (APU) in the penis before (P = 0.5808) and after SIL (P = 0.4256) were similar in the control and hypertensive subjects. Penile baseline microvascular flow was significantly increased after SIL in control (P = 0.0006) and also in hypertensive (P = 0.0038) subjects, compared to basal values before SIL. The basal values of CVC in the penis before (P = 0.0590) and after (P = 0.0857) SIL in the control and hypertensive participants were not significantly different. The peak values of CVC during iontophoresis of ACh in the penis before SIL were of 0.62 (0.44–0.91) and 0.50 (0.33–0.79) APU/mmHg in the control and hypertensive participants, respectively (P = 0.2052). After administration of SIL, the peak values of CVC during iontophoresis of ACh in the penis were of 0.88 (0.66–1.12) and 0.69 (0.56–0.84) APU/mmHg in the control and hypertensive participants, respectively (P = 0.0427). Conclusions: Penile endothelium-dependent microvascular function was similar in hypertensive patients and healthy controls. Nevertheless, the response to the acute administration of SIL was higher in the controls than in hypertensive patients.

Acute Activation of the Peripheral Chemoreceptors Briefly Induces Cutaneous Vasoconstriction

Recent evidence indicates that five minutes of breathing hypoxic gas elicits cutaneous vasodilation. However, it is unclear if skin blood flow is influenced by a brief hypoxic exposure. PURPOSE: We tested the hypothesis that cutaneous vasodilation is increased following a brief hypoxic exposure. METHODS: Seven healthy participants (2 women, 25 ± 2 years, BMI 26 ± 3 kg/m2) breathed 4–6 breaths of 100% nitrogen. We continuously measured skin blood flow on the ventral side of the forearm (laser Doppler), arterial oxygen saturation (finger pulse oximeter), mean arterial pressure (Finometer), and heart rate (ECG) at baseline and following the hypoxic exposure for one minute, during which data were analyzed in 15 s time bins. Skin blood flow was also normalized to mean arterial pressure (MAP) and expressed as a percentage of the local heating induced maximal cutaneous vascular conductance (%CVCmax). RESULTS: Arterial oxygen saturation was lower at 45 s (89 ± 7%; P < 0.05) and 60 s (90 ± 5%; P < 0.05) vs. baseline (97 ± 1%). Skin blood flow was lower 15 s after the hypoxic exposure when compared to baseline (4.2 ± 0.9 vs. 5.1 ± 0.9 PU, P = 0.001). MAP was greater at 15 s vs. baseline (94 ± 7 vs. 88 ± 7 mmHg; P < 0.05) and returned to baseline values at 30 s. %CVCmax was reduced within the first 15 s following the hypoxic exposure compared to baseline (4.3 ± 1.0 vs. 5.6 ± 1.2%; P < 0.05). Skin blood flow and %CVCmax returned to baseline values 30 s following the hypoxic exposure. Heart rate was significantly greater than baseline (64 ± 9 bpm) at 15 s (76 ± 13 bpm; P < 0.01), 30 s (76 ± 14 bpm; P < 0.01), 45 s (69 ± 11 bpm; P < 0.01), and 60 s (67 ± 11 bpm; P < 0.05). CONCLUSIONS: Contrary to our hypothesis, a brief hypoxic exposure induces cutaneous vasoconstriction and attenuates skin blood flow. This suggests that activation of the peripheral chemoreceptors acutely lowers skin blood flow.

Endothelin‐B Receptor Responses in Young and Postmenopausal Women

Cardiovascular disease (CVD) is the leading cause of the death in women, and postmenopausal women (PMW) are at an increased risk for developing CVD. Endothelin‐1 (ET‐1) contributes to age‐related endothelial dysfunction in men via the ETA receptor. However, there are sex differences in ET‐1 regulation of vascular function, and ETB receptors are influenced by fluctuations in ovarian hormones.PURPOSEThe purpose of this study was to test the hypothesis that ETB receptors contribute to impaired microvascular function in PMW.METHODSWe measured skin blood flow (SkBF) in 11 young women (YW; 22±1 years, 22±1 kg/m2) and 10 PMW (58±2 years, 24±1 kg/m2) using laser Doppler flowmetry during microdialysis perfusions of lactated Ringer's (control), an ETB receptor antagonist (BQ‐788, 300nM), and an ETA receptor antagonist (BQ‐123, 500 nM). We utilized local skin heating (42°C) to induce microvascular vasodilation, followed by perfusion of sodium nitroprusside (28mM) to elicit maximal dilation. Mean arterial blood pressure (MAP) was measured throughout. Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP during the plateau established during local heating, and expressed as a percent of maximal dilation. Unpaired t‐tests were used to compare variables between YW and PMW.RESULTSResting MAP was higher in PMW (93±2 mmHg) compared to YW (80±2 mmHg; P&lt;0.05). Vasodilatory responses to local heating (control site) tended to be lower in PMW (YW: 91±2 vs. PMW: 81±5 CVC % max; P=0.12). ETB receptor blockade tended to decrease cutaneous vasodilation in YW (control: 91±2 vs. BQ‐788: 85±3 CVC % max; P=0.08), but tended to enhanced vasodilation in PMW (control: 81±5 vs. BQ‐788: 92±1 CVC % max; P=0.08). ETA receptor blockade had minimal effect in YW (control: 91±2 vs. BQ‐123: 92±2 CVC % max; P=0.35), but tended to increase cutaneous vasodilation in PMW (control: 81±5 vs. BQ‐123: 90±2 CVC % max; P=0.11).CONCLUSIONETB receptors appear to mediate vasodilation in YW. However, microvascular vasodilation is blunted in PMW, possibly due to greater ETB and ETA mediated vasoconstriction.Support or Funding InformationSupported by NIH Grant U54 GM 104941 01A1 and University of Delaware Research Foundation.

Effect of Physiological Changes in the Skin on Systemic Absorption of Tacrolimus Following Topical Application in Rats.

Tacrolimus (TL) ointment is a topical treatment for atopic dermatitis, a disease that exhibits various skin conditions. The effect of skin pathologies on the systemic absorption of TL and related side effects remains unknown. This study aimed to investigate factors affecting the cutaneous absorption of TL. We prepared various skin models in hairless rats by tape stripping, injection of prophlogistic material solution (PMS), and continuous subcutaneous adrenaline (Adr) infusion. In vivo absorption studies were conducted, with measurements of transepidermal water loss (TEWL) and skin blood flow as physiological parameters. Very little TL absorption was observed through intact skin. Greater TL absorption was noted in skins with high TEWL values and fully stripped skin with PMS injections. In contrast, Adr infusion, which reduced skin blood flow, resulted in decreased TL absorption through fully stripped skin. Combined use of TL and Adr on skin with PMS injections resulted in suppression of TL absorption. Our results revealed that TL absorption following topical application is affected by alterations in the skin barrier, blood flow, and vascular permeability. We propose an administration plan for TL in a flowchart as a means of preventing systemic side effects.

Changes in Cortical Oxyhaemoglobin Signal During Low-Intensity Cycle Ergometer Activity: A Near-Infrared Spectroscopy Study.

Near-infrared spectroscopy (NIRS) is a widely used non-invasive method for measuring human brain activation based on the cerebral hemodynamic response during gross motor tasks. However, systemic changes can influence measured NIRS signals. We aimed to determine and compare time-dependent changes in NIRS signal, skin blood flow (SBF), and mean arterial pressure (MAP) during low-intensity, constant, dynamic exercise. Nine healthy volunteers (22.1±1.7 years, 3 women) participated in this study. After a 4-min pre-exercise rest and a 4-min warm-up, they exercised on a bicycle ergometer at workloads corresponding to 30% VO2 peak for 20 min. An 8-min rest period followed the exercise. Cortical oxyhaemoglobin signals (O2Hb) were recorded while subjects performed the exercise, using an NIRS system. Changes in SBF and MAP were also measured during exercise. O2Hb increased to 0.019 mM cm over 6 min of exercise, decreased slightly from 13 min towards the end of the exercise. SBF continued to increase over 16 min of the exercise period and thereafter decreased till the end of measurement. MAP fluctuated from -1.0 to 7.1 mmHg during the exercise. Pearson's correlation coefficients between SBF and O2Hb, and MAP and O2Hb differed in each time phase, from -0.365 to 0.713. During low-intensity, constant, dynamic exercise, the profile of changes in measurements of O2Hb, SBF, and MAP differed. These results suggested that it is necessary to confirm the relationship between O2Hb and systemic factors during motor tasks in order to detect cortical activation during gross motor tasks.

Acetylsalicylic acid does not alter thermo-effector responses during mild whole-body passive heat stress in young men

Acetylsalicylic acid (ASA), aspirin, exerts potent systemic effects that may interfere with normal thermo-effector responses. We investigated the influence of commonly ingested ASA doses on measures of skin blood flow (SkBF) and local sweat rate (SR) during whole-body, passive heat stress. Seven male participants completed counter-balanced trials to compare ASA treatments (single dose 325 mg or 4 consecutive days 81 mg (4-d 81 mg)) to control (no ASA). Laser-Doppler flowmetry provided an index of SkBF. A ventilated capsule measured local sweat rate via capacitance hygrometry. Mean body temperature () was increased by 1 °C above baseline using a water-perfused suit. was similar at the onset of cutaneous vasodilation among trials. Cutaneous vascular conductance, expressed as a percentage change from baseline, was not different among trials. Additionally, at the onset of local SR and SR sensitivity did not differ among trials. While ASA has previously been shown to influence SkBF during heat stress, it is possible our cohort’s relatively young age may have contributed to our dissimilar results.

Evidence that reduced nitric oxide signal contributes to cutaneous microvascular dysfunction in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with cutaneous microvascular dysfunction and an increased risk of arterial ulceration in the affected lower-limb(s). The purpose of this study was to investigate the role of nitric oxide (NO) in cutaneous microvascular dysfunction in patients with PAD. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in 5 patients with unilateral symptomatic PAD and 10 age-matched healthy controls at baseline and during 40 min of local skin heating to 42°C at 1) untreated lower-leg sites, and 2) lower-leg sites treated with 20 mM N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase activity. SkBF was expressed as laser-Doppler flux (LDF) and normalized to maximal LDF (%LDF(max)) achieved through localized heating to 44°C and concomitant infusion of 56 mM sodium nitroprusside. Pharmacological agents and control treatments (lactated Ringer's) were administered using intradermal microdialysis. The plateau LDF response to local skin warming at the untreated skin sites was significantly (P<0.05) lower in the diseased limb of the PAD patients (70.3±13.6 %max) compared to the non-diseased contralateral limb (85.0±10.2 %max) and the response observed for the control participants (89.0±5.2 %max). The NO contribution to the plateau SkBF response tended to be lower in the diseased limb of the PAD patients (45.1±16.4% versus 56.1±10.7% [P=0.12] and 55.4±11.5% [P=0.13], respectively). The results suggest that PAD impairs downstream cutaneous microvascular vasodilatory function and that the microvascular dysfunction is probably explained, at least in part, by a reduced NO signal.

Locally Injected Dexmedetomidine Induces Vasoconstriction via Peripheral α-2A Adrenoceptor Subtype in Guinea Pigs

Recent research shows that locally injected dexmedetomidine enhances the local anesthetic potency of lidocaine via the α-2A adrenoceptor subtype in guinea pigs. However, little is known about the effect of locally injected dexmedetomidine on the peripheral vascular response. This study aimed to evaluate the effect of locally injected dexmedetomidine on the peripheral vascular response, measuring skin blood flow in the injected area in guinea pigs. Dexmedetomidine was intracutaneously injected at a volume of 0.1 mL into the backs of guinea pigs, and further injected combined with yohimbine, a selective antagonist of α-2 adrenoceptors, or prazosin, a selective antagonist of α-1 adrenoceptors and an antagonist of both α-2B and α-2C adrenoceptor subtypes. Skin blood flow was measured until 60 minutes after injection using a laser-Doppler flowmeter. Furthermore, systemic arterial blood pressure and pulse of the guinea pigs were monitored via a catheter inserted into the carotid artery throughout every experiment. Dexmedetomidine at a concentration of 1 μM significantly decreased the skin blood flow in a dose-dependent manner with no changes in the mean blood pressure and pulse. Yohimbine completely antagonized the effect of dexmedetomidine, but prazosin did not. The results reveal that locally injected dexmedetomidine at a concentration of 1 μM induced peripheral vasoconstriction without a systemic cardiovascular response via the peripheral α-2A adrenoceptor subtype.

Development of a hybrid microwave-optical thermoregulation monitor for the muscle.

This paper presents the latest development of the hybrid microwave-optical thermoregulation monitor for the muscle. It is capable of warming the muscle and measuring the subsequent blood volume changes, using a novel microwave applicator with integrated optical probes. The challenge is to measure the thermoregulation response in deep tissue while minimizing any effect from the skin layer. We have introduced a skin cooling device, an additional integrated optical Laser Doppler flow monitoring probe and a temperature sensor to measure skin blood flow and temperature, respectively. The result shows that skin cooling is essential to minimize skin flow changes during microwave warming. The hybrid probe was placed on a human thigh to measure oxy/deoxy/total haemoglobin concentration changes (ΔHbO₂/ΔHHb/ΔHbT), skin flux and temperature upon microwave warming. Without skin cooling, the skin temperature was elevated by 4 °C and both ΔHbO₂/ΔHbT and skin flux increased, showing microwave warming occurring in both the skin and muscle. With skin cooling, the skin temperature was kept relatively constant. While ΔHbO₂/ΔHbT increased, the skin flux was relatively stable, showing a preferential microwave warming in the muscle, rather than the skin.

Skin blood flow as a predictor of intraventricular hemorrhage in very-low-birth-weight infants

Cardiovascular instability immediately after birth is associated with intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants. For circulatory management, evaluation of organ blood flow is important. In this study, the relationship between peripheral perfusion within 48 h after birth and IVH was evaluated in VLBW infants. In this prospective observational study involving 83 VLBW infants, forehead blood flow (FBF) and lower-limb blood flow (LBF) were measured for 48 h after birth using a laser Doppler flowmeter. Blood flow was compared between infants with and without IVH. Multivariate logistic regression analysis was performed to identify the risk factors for IVH. IVH developed in nine infants. In eight of these patients, IVH occurred after 24 h. LBF was lower in infants with IVH at 18 and 24 h and increased to the same level as that of infants without IVH at 48 h. Multivariate logistic regression analysis identified a correlation only between LBF and IVH at 18 h. These findings were consistent with the hypoperfusion-reperfusion theory, which states that IVH develops after reperfusion subsequent to hypoperfusion. We speculate that measurement of skin blood flow in addition to systemic and cerebral circulation may be helpful in predicting IVH.

Laser Doppler imaging for assessment of microcirculation in juvenile systemic sclerosis

The objectives of this study were to evaluate the dynamic behaviour of digital skin microvascular blood flow before and after cold stimulation using laser Doppler imaging (LDI) in children and adolescents with RP secondary to juvenile systemic sclerosis (JSS), primary RP (PRP) and healthy controls and to compare functional abnormalities measured by LDI with structural microvascular abnormalities evaluated by nailfold capillaroscopy (NFC). Five JSS patients, five children and adolescents with PRP and five healthy controls matched for gender and age were included. All subjects had NFC performed. Finger blood flow (FBF) was measured using the LDI system (Moor Instruments) at baseline and after cold stimulus (CS). There were a decreased number of capillaries, a greater number of enlarged capillaries and a higher deletion score in JSS patients compared with controls and patients with PRP. The mean baseline FBF was significantly lower in JSS patients compared with controls. There was no difference between the mean baseline FBF in JSS patients compared with patients with PRP. There was a significant decrease in FBF 1 min after CS in all groups followed by blood flow recovery at 20 min after CS in comparison with basal FBF values in controls, but not in JSS and PRP patients. In JSS patients, LDI showed a lower FBF before and after CS compared with healthy controls and may be an objective and sensitive method for the measurement of digital skin blood flow in RP children.

Individuals with early onset (premature) coronary artery disease display impaired systemic microvascular endothelial function: studies using laser speckle contrast imaging

Purpose: Laser speckle contrast imaging (LSCI) provides an innovative approach to the non-invasive evaluation of systemic microvascular endothelial function. In the present work, we assessed skin microvascular reactivity in individuals with early onset coronary artery disease (EOCAD, diagnosis at less than 45 years of age) using LSCI coupled to pharmacological and physiological stimuli. Methods: Skin microvascular blood flow was continuously monitored in the forearm using LSCI. Acetylcholine (ACh) dose-response curves were performed using an iontophoresis micropharmacology system and post-occlusive reactive hyperemia (PORH) was analyzed after a 3-minute occlusion of blood flow to the forearm. Measurements of microvascular skin blood flow in arbitrary perfusion units (APU) were divided by mean arterial pressure to give cutaneous vascular conductance (CVC) in APU/mm Hg. The results were presented as mean ± SEM and were analyzed using two-tailed unpaired Student's t tests. Results: Fifty-eight patients with EOCAD aged 45±0.4 years (34 men) and 25 healthy age- and sex-matched individuals were included in the study. ACh- and PORH-mediated vasodilation was significantly reduced in EOCAD individuals. Area under the curve of ACh-induced vasodilation was of 6445±842 and 3975±540 APU/sec in controls vs. EOCAD, respectively; p=0.0087; figure 1). Increase in CVC resulting from PORH-induced vasodilation was of 0.46±0.03 and 0.38±0.02 APU/mmHg in controls vs. EOCAD, respectively; p=0.0182; figure 1). ![Figure][1] Conclusions: LSCI identifies systemic microvascular endothelial-dysfunction in individuals presenting with EOCAD and thus could be used as an early peripheral marker of the atherothrombotic disease. [1]: pending:yes

Skin blood flow response to locally applied mechanical and thermal stresses in the diabetic foot

Diabetic foot ulcers are one of the most common complications in diabetics, causing significant disabilities and decreasing the quality of life. Impaired microvascular reactivity contributes to the development of diabetic foot ulcers. However, underlying physiological mechanisms responsible for the impaired microvascular reactivity in response to extrinsic causative factors of foot ulcers such as mechanical and thermal stresses have not been well investigated. A total of 26 participants were recruited into this study, including 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls. Laser Doppler flowmetry was used to measure skin blood flow at the first metatarsal head in response to a mechanical stress at 300mmHg and a fast thermal stress at 42°C. Wavelet analysis of skin blood flow oscillations was used to assess metabolic, neurogenic and myogenic controls. Our results indicated that diabetics have significantly decreased metabolic, neurogenic and myogenic responses to thermal stress, especially in the neurogenic and myogenic controls during the first vasodilatory response and in the metabolic control during the second vasodilatory response. Diabetics have a significantly decreased myogenic response to mechanical stress during reactive hyperemia. Our findings demonstrate that locally applied mechanical and thermal stresses can be used to assess microvascular reactivity and risk of diabetic foot ulcers.

Effect of skin temperature on skin endothelial function assessment

PurposeMicrocirculatory dysfunction plays a key role in the development of sepsis during which core temperature is often disturbed. Skin microvascular assessment using laser techniques has been suggested to evaluate microvascular dysfunction during sepsis, but skin microcirculation is also a major effector of human thermoregulation. Therefore we aimed to study the effect of skin temperature on endothelial- and non-endothelial microvascular responses. MethodsFifteen healthy participants were studied at different randomized ambient temperatures leading to low (28.0+/−2.0°C), intermediate (31.6+/−2.1°C), and high (34.1+/−1.3°C) skin temperatures. We measured skin blood flow using laser speckle contrast imaging on the forearm in response to vasodilator microvascular tests: acetylcholine (ACh) iontophoresis, sodium nitroprussiate (SNP) iontophoresis, and post-occlusive reactive hyperemia (PORH). The results are expressed as absolute (laser speckle perfusion units, LSPU) or normalized values (cutaneous vascular conductance, CVC in LSPU/mmHg and multiple of baseline). ResultsMaximal vasodilation induced by these tests is modified by skin temperature. A low skin temperature induced a significant lower vasodilation for all microvascular tests when results are expressed either in absolute values or in CVC. For example, ACh peak was 57.6+/−19.6LSPU, 66.8+/−22.2LSPU and 88.5+/−13.0LSPU for low, intermediate and high skin temperature respectively (p<0.05). When results are expressed in multiple of baseline, statistical difference disappeared. ConclusionsThese results suggest that skin temperature has to be well controlled when performing microvascular assessments in order to avoid any bias. The effect of skin temperature can be corrected by expressing the results in multiple of baseline.

Viscerosympathetic reflexes in human spinal cord injury: relationships between detrusor pressure, blood pressure and skin blood flow during bladder distension

Autonomic dysreflexia, a dangerous and sustained increase in blood pressure brought about by widespread, reflexly generated vasoconstriction, can be induced by visceral or somatic sensory inputs originating below the lesion following spinal cord injury (SCI). We assessed whether cutaneous vasoconstriction below the lesion could serve as a proxy marker of incipient autonomic dysreflexia during bladder distension. Skin blood flow (pulse plethysmography), sweat release, blood pressure, heart rate, bladder and rectal pressures were recorded during routine cystometry (urodynamics) in 16 patients with SCI. Eight urological patients without SCI served as control subjects. In all SCI patients, who had sustained injuries 2 months to 44 years previously at levels C3-T3, bladder filling (mean ± SD, 339 ± 132 ml) induced increases in detrusor (bladder-rectal) pressure (52 ± 25 cmH(2)O) and cutaneous vasoconstriction in the fingers, but no consistent increases in sweat release. This occurred irrespective of whether the spinal lesions were complete [American Spinal Injury Association (ASIA) grade A, n = 6] or incomplete (ASIA B-D; n = 10). Group mean blood pressure for the SCI patients increased by 17 ± 15 mmHg, but in four patients the pressure decreased or did not change. Despite similar bladder volumes (423 ± 126 ml) in the control patients, the increases in detrusor pressure (14 ± 8 cmH(2)O) and blood pressure (9 ± 12 mmHg) were significantly smaller than in the SCI patients; moreover, there were no consistent changes in skin blood flow in the control subjects. In all SCI patients, changes in finger pulse amplitudes were inversely correlated to changes in detrusor pressure (mean r = -0.62 ± 0.17). Changes in finger pulse amplitudes correlated inversely to changes in blood pressure in nine of 15 patients. It is concluded that cystometry in SCI patients is associated with detrusor and cardiovascular reflex effects that are exaggerated compared with those in intact subjects and that measurement of skin blood flow from the fingers in patients with a high spinal lesion provides a supplementary, clinically useful, non-invasive and continuous marker of spinally mediated viscerosympathetic reflex activity below the lesion in such patients.