Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at the cutaneous level.

AIMS: Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake. METHODS: Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline. RESULTS: Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days. CONCLUSIONS: This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.

Cutaneous microvascular functional assessment during exercise: a novel approach using laser speckle contrast imaging.

Cardiovascular diseases are often revealed during exercise and are associated with cutaneous blood flow (CBF) dysfunction. Studies of CBF during exercise are consequently of interest. Laser speckle contrast imaging (LSCI) allows for non-contact and real-time recording of CBF at rest. We tested whether LSCI could allow the study of CBF during a cycling exercise using a specific signal treatment procedure that removes movement-induced artefacts from the LSCI raw signal. We recorded the baseline CBF and peak post-occlusive reactive hyperaemia (PORH) from the cutaneous forearm using LSCI and the mean blood pressure before and during cycling (80 W at 70 rpm) in nine healthy subjects. We determined the cross-correlation coefficient r between LSCI traces obtained before and during cycling and before and after a specifically designed signal processing technique. The results are presented as the median (25th-75th centile) and expressed as the cutaneous vascular conductance (laser speckle perfusion units (LSPU) per millimetre of mercury). Cross-correlation r increased from 0.226 ± 0.140 before to 0.683 ± 0.170 after post-processing. After signal processing, the peak PORH during exercise was reduced [0.38 (0.30-0.52) LSPU/mmHg] compared with the peak PORH during the non-exercise phase [0.69 (0.63-0.74) LSPU/mmHg, p < 0.01], whereas no difference was found between the baseline values. With adequate signal processing, LSCI appears valuable for investigating CBF during exercise. During constant-load lower limb cycling exercise, the upper limb peak PORH is reduced compared with the peak PORH during non-exercise. The underlying mechanisms warrant further investigations in both healthy (trained) subjects and diseased (e.g., coronary heart disease) patients.

Neurovascular microcirculatory vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes.

Microvascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced vasodilation, CIV) microcirculatory vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP vasodilations. Neurovascular microcirculatory vasodilations (C-fibers and TRPV 1-mediated vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.

Aging effect on microcirculation: A multiscale entropy approach on laser speckle contrast images.

PURPOSE: It has long been known that age plays a crucial role in the deterioration of microvessels. The assessment of such deteriorations can be achieved by monitoring microvascular blood flow. Laser speckle contrast imaging (LSCI) is a powerful optical imaging tool that provides two-dimensional information on microvascular blood flow. The technique has recently been commercialized, and hence, few works discuss the postacquisition processing of laser speckle contrast images recorded in vivo. By applying entropy-based complexity measures to LSCI time series, we present herein the first attempt to study the effect of aging on microcirculation by measuring the complexity of microvascular signals over multiple time scales. METHODS: Forearm skin microvascular blood flow was studied with LSCI in 18 healthy subjects. The subjects were subdivided into two age groups: younger (20-30 years old, n = 9) and older (50-68 years old, n = 9). To estimate age-dependent changes in microvascular blood flow, we applied three entropy-based complexity algorithms to LSCI time series. RESULTS: The application of entropy-based complexity algorithms to LSCI time series can differentiate younger from older groups: the data fluctuations in the younger group have a significantly higher complexity than those obtained from the older group. CONCLUSIONS: The effect of aging on microcirculation can be estimated by using entropy-based complexity algorithms to LSCI time series.

[Endothelial function: role, assessment and limits]. / La fonction endothéliale : rôle, méthodes d'évaluation et limites.

For several years, detecting and preventing cardiovascular diseases have become a major issue. Different methods have been developed to evaluate endothelial function. Endothelial dysfunction is one of the first steps leading to atherosclerosis. This review presents an insight into endothelial function, the interests of its assessment and methods for studying endothelial function. To date, the vascular endothelium must be considered as a specific organ with its own functions that contribute to the homeostasis of the cardiovascular system. Endothelial dysfunction typically corresponds to a decrease of nitric oxide NO bioavailability. Biological or physico-chemical methods may be used to assess dysfunction. Biological methods allow measuring NO metabolites and pro-inflammatory and vasoconstrictor mediators released by the endothelium. The physico-chemical methods include intra-coronary injections, plethysmography, flow-mediated dilation (FMD), digital plethysmography and optical techniques using laser (laser Doppler single-point, laser Doppler imager, laser speckle contrast imaging) that can be coupled with provocation tests (iontophoresis, microdialysis, post-ischemic hyperemia, local heating). The principle of each technique and its use in clinical practice are discussed. Studying endothelial dysfunction is a particularly promising field because of new drugs being developed. Nevertheless, assessment methodology still needs further development to enable reliable, non-invasive, reproducible, and inexpensive ways to analyze endothelial dysfunction.

Relevance of laser Doppler and laser speckle techniques for assessing vascular function: state of the art and future trends.

In clinical and research applications, the assessment of vascular function has become of major importance to evaluate and follow the evolution of cardiovascular pathologies, diabetes, hypertension, or foot ulcers. Therefore, the development of engineering methodologies able to monitor noninvasively blood vessel activities-such as endothelial function-is a significant and emerging challenge. Laser-based techniques have been used to respond-as much as possible-to these requirements. Among them, laser Doppler flowmetry (LDF) and laser Doppler imaging (LDI) were proposed a few decades ago. They provide interesting vascular information but possess drawbacks that prevent an easy use in some clinical situations. Recently, the laser speckle contrast imaging (LSCI) technique, a noninvasive camera-based tool, was commercialized and overcomes some of the LDF and LDI weaknesses. Our paper describes how-using engineering methodologies-LDF, LDI, and LSCI can meet the challenging clinician needs in assessing vascular function, with a special focus on the state of the art and future trends.

A new laser Doppler flowmeter prototype for depth dependent monitoring of skin microcirculation.

Laser Doppler flowmetry (LDF) is now commonly used in clinical research to monitor microvascular blood flow. However, the dependence of the LDF signal on the microvascular architecture is still unknown. That is why we propose a new laser Doppler flowmeter for depth dependent monitoring of skin microvascular perfusion. This new laser Doppler flowmeter combines for the first time, in a device, several wavelengths and different spaced detection optical fibres. The calibration of the new apparatus is herein presented together with in vivo validation. Two in vivo validation tests are performed. In the first test, signals collected in the ventral side of the forearm are analyzed; in the second test, signals collected in the ventral side of the forearm are compared with signals collected in the hand palm. There are good indicators that show that different wavelengths and fibre distances probe different skin perfusion layers. However, multiple scattering may affect the results, namely the ones obtained with the larger fibre distance. To clearly understand the wavelength effect in LDF measurements, other tests have to be performed.