Blood Flux Research Articles

Cardiovascular and metabolic responses to tap water ingestion in young humans: does the water temperature matter?

Drinking water induces short-term cardiovascular and metabolic changes. These effects are considered to be triggered by gastric distension and osmotic factors, but little is known about the influence of water temperature. We determined, in a randomized crossover study, the acute cardiovascular and metabolic responses to 500 mL of tap water at 3 °C (cold), 22 °C (room) and 37 °C (body) in 12 young humans to ascertain an effect of water temperature. We measured continuous beat-to-beat haemodynamics, skin blood flux with laser-Doppler flowmetry and resting energy expenditure by indirect calorimetry starting with a 30-min baseline followed by a 4-min drink period and a subsequent 90-min post-drink observation. Ingestion of cold- and room-tempered water led to decreased heart rate (P < 0.01) and double product (P < 0.01), and increased stroke volume (P < 0.05); these effects were not observed with body-tempered water. Drinking cold- and room-, but not body-tempered water, led to increased high frequency power of heart rate variability (P < 0.05) and baroreflex sensitivity (P < 0.05). Cold- and room-tempered water increased energy expenditure over 90 min by 2.9% (P < 0.05) and 2.3% (ns), respectively, accompanied by a diminished skin blood flux (P < 0.01), thereby suggesting that both small increases in heat production together with decreased heat loss contribute to warming up the ingested water to intra-abdominal temperature levels. Overall, ingestion of cold- and room-, but not body-tempered water reduced the workload to the heart through a reduction in heart rate and double product which could be mediated by an augmented cardiac vagal tone.

Impact of long-term exposure to cigarette smoking on skin microvascular function

In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11years; range: 18 to 86years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009–0.02Hz, 0.021–0.06Hz and 0.061–0.2Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3–183.0) vs 190.1% (156.3–216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.

Aging-related differences in cerebral capillary blood flow in anesthetized rats

Age-related decreases in baseline cerebral blood flow have been measured with various imaging modalities, however, the contribution of capillary flow to this phenomenon remain to elucidate. This study used 2-photon laser scanning fluorescence microscopy to measure capillary diameter, red blood cell speed, and flux in individual capillaries in the sensory-motor cortex of 12 adult (3-month-old) and 12 old (24-month-old) male Long-Evans rats under isoflurane anesthesia. The average (± standard deviation) diameter and speed over 921 capillaries were 6.4 ± 1.4 μm and 1.3 ± 1.1 mm/s, respectively. Red blood cell speed and flux were significantly higher, by 48% and 15%, respectively, in old compared with young animals (p < 5%). The diameter also showed a similar tendency (7% higher, p = 5.7%). Furthermore, capillary hematocrit and density were significantly lower in the older group (p < 5%), by 32% and 20%, respectively.

Decreased microvascular myogenic response to insulin in severely obese adolescents

By means of flowmotion analysis, it is mainly accepted that, in normal conditions, insulin specifically increases the activity of microvascular smooth muscle. The objective of this study was to compare this effect in severely obese and normal-weight adolescents. Laser Doppler measurements were used to assess cutaneous blood flux (CBF) and flowmotion in response to transdermal iontophoresis of insulin in 20 severely obese adolescents (SOA) aged 12-17 years (BMI = 33.34 ± 1.07 kg/m2), and 16 normal-weight adolescents (BMI = 18.85 ± 0.50 kg/m2). Fasting insulin levels were higher in SOA than in normal-weight adolescents (6.25 ± 1.03 vs. 3.11 ± 0.28 μU/ml, P = 0.007). Net insulin-induced increase of CBF did not significantly differ between SOA and normal-weight adolescents (422.41 ± 146.09 vs. 232.36 ± 80.98 %, P = 0.265). A significant impairment of myogenic flowmotion was detected in SOA compared to normal-weight adolescents in response to insulin delivery (5.91 ± 0.35 vs. 8.12 ± 0.63 %, P = 0.003). Severely obese adolescents exhibit decreased myogenic activity in response to insulin, which may be an early step in the development of insulin resistance.

Effects of various drugs (flunixin, pentoxifylline, enoxaparin) modulating micro-rheological changes in cerulein-induced acute pancreatitis in the rat

Previously we have investigated the cerulein-induced acute pancreatitis and provided data on its micro-rheological impact in the rat. We hypothesized that non-steroid anti-inflammatory agent flunixin, the xanthine-derivate pentoxifylline and the low molecular weight heparin enoxaparin may have various beneficial effects improving microcirculatory and rheological parameters. In female rats, under general anesthesia, 10 μg/kg cerulein s.c. was administered and 2 hours afterwards microcirculation was tested by laser Doppler flowmetry on the tongue and after performing laparotomy on the small intestine, liver and pancreas prior to terminal blood sampling. From blood samples hematological parameters, blood pH, lactate concentration, erythrocyte deformability, osmoscan parameters and erythrocyte aggregation were tested. Compared to normal control in acute pancreatitis group we found severe deterioration in tissue microcirculation together with impaired erythrocyte deformability and enhanced aggregation, accompanied by acidic pH and increasing lactate concentration. Improvement was found when using flunixin (s.c.), pentoxifylline (i.p.) or enoxaparin (s.c.). These drugs could partly improve the blood flux on the surface of the investigated organs, and the flunixin had the most expressed improving effects on micro-rheological parameters. Surprisingly, the improving effect of pentoxifylline on micro-rheological parameters was not obvious (red blood cell deformability did not improved better than in the other treated groups), however, microcirculatory parameters improved.

Hemodynamic Impact of Absent or Reverse End-Diastolic Flow in the Two Umbilical Arteries in Growth-Restricted Fetuses

ObjectiveTo determine if bilateral absent or reverse end-diastolic (ARED) flow in the two umbilical arteries (UAs) at the perivesical (PVC) segment represents a more severe degree of hemodynamic compromise than unilateral ARED flow at the PVC segment in singleton pregnancies complicated by intrauterine growth restriction (IUGR).MethodsThis was a prospective observational study. One hundred nine fetuses with IUGR underwent a total of 225 ultrasound (US) examinations. We measured the pulsatility index (PI) from the two UAs at the PVC segment, UA in the free floating cord (FFC), middle cerebral artery (MCA), ductus venosus (DV) and the aortic isthmus blood flow index (IFI). Three groups were classified according to bilateral positive end-diastolic (PED) flow, unilateral ARED flow or bilateral ARED flow in the UAs at the PVC segment.ResultsThe proportions of US examinations with PED flow, unilateral ARED flow and bilateral ARED flow in the UAs were 54.7%, 20.4%, and 24.9%, respectively. At the last US examination, the IFI z-scores were significantly lower in the bilateral ARED group (-6.28±4.30) compared to the unilateral ARED group (-1.72±3.18, p<0.05) and the bilateral PED group (-0.83±2.36, p<0.05), the DV-PI z-scores were significantly higher in the bilateral ARED group (2.15±3.79) compared to the bilateral PED group (0.64±1.50, p<0.05). Before 32 weeks of gestation, the interval between US examination and delivery was significantly shorter in the bilateral ARED group (8.9 days ±8.2) than the unilateral ARED group (15.9 days ±13.4, p<0.05) and the bilateral PED group (30.3 days±25.7, p<0.05).ConclusionThere are significant differences in fetal blood fluxes between left and right UA. Doppler examination at the PVC segment significantly improves the comparability of UA-PI between two successive US examinations and allows a longitudinal and independent hemodynamic investigation of each UA. Examination of a single UA in free floating cord may miss a large fraction of unilateral ARED flow. In singleton IUGR fetuses, a bilateral ARED flow in the UAs at the PVC segment indicates more severe hemodynamic compromise and worse fetal conditions than unilateral ARED flow.

Non-Invasive Contrast Ultrasound Imaging Of Abnormal Microvascular Perfusion and Reduced Functional Blood Volume In Sickle Cell Disease

IntroductionVaso-occlusive events play a role in the pathophysiology of sickle cell disease (SCD) and are a potential target for new therapies. There is strong evidence that platelet and endothelial activation as well as microvascular dysfunction contribute to this process. Techniques capable of spatially and temporally assessing basal or provoked tissue hypoperfusion in animal models or in patients with SCD would be valuable for evaluating new therapies. Contrast enhanced ultrasound (CEU) is a non-invasive imaging technique that relies on the ultrasound detection of microbubble contrast agents during their microvascular transit. In this study we hypothesized that CEU perfusion imaging would provide a biologic readout for abnormalities in skeletal muscle perfusion in a murine model of SCD. Materials and MethodsNY1DD mice with either homozygous (n=16) or heterozygous (n=18) gene deletion of murine β globin that also transgenically express human α and βsglobin were studied at 8-10 weeks of age, while C57/BL6 mice (n=7) were used as controls. Animals were studied under basal conditions only if they appeared healthy and not in distress or pain crisis equivalent. Mice were anesthetized with inhaled isoflurane and a jugular vein was cannulated for contrast administration. CEU perfusion imaging of the proximal hindlimb adductor muscles and the myocardium was performed using continuous intravenous infusions of lipid-shelled decafluorobutane microbubbles. Time-activity curves from real-time imaging following a disruptive high power ultrasound pulse sequence was used to quantify both microvascular blood flow (MBF) and its parametric components: functional microvascular blood volume (MBV) and flux rate (β). Skeletal muscle CEU was performed at rest and during electrostimulated contractile exercise at 1 Hz. Spatial analysis of perfusion was done to assess average percent area of perfusion per areas of tissue. High-frequency echocardiography was performed to evaluate LV dimensions and stroke volume. ResultsSkeletal muscle MBF was significantly lower in NY1DD mice compared to controls, the extent of which was similar for the two NY1DD cohorts (MBF= 1.11±0.84, 0.58±0.77, 0.48±0.35 for control, homozygous, and heterozygous NY1DD mice, respectively; Kruskall-Wallis p<0.05). Microbubble microvascular flux rate was similarly reduced by approximately half in both NY1DD groups compared to controls (p<0.01). Skeletal muscle MBV was reduced only in the homozygous NY1DD mice (approximately 70% the volume of controls). Spatial analysis of MBV revealed coarse rather than diffuse spatial hypoperfusion in the homozygous NY1DD mice, indicating lack of perfusion downstream from large intramuscular vascular units. Electrostimulated exercise produced a significant increase in skeletal muscle MBF in all groups, although hyperemic blood flow remained 60-70% lower than controls for both NY1DD groups. In contrast to skeletal muscle perfusion, myocardial MBF was increased in NY1DD mice, largely due to increased flux rate. Echocardiography demonstrated a similar stroke volume and cardiac output between animals. ConclusionsCEU perfusion imaging can be used to non-invasively detect microvascular abnormalities in murine models of SCD. Even under basal resting conditions, there is a reduction in skeletal muscle MBF. The reduction in microvascular flux rate under basal conditions and presence of MBF reserve in mice with SCD strongly suggest that abnormalities in MBF at rest were to a large extent functional in nature rather than obstructive. From spatial analysis, this appears to involve medium to large intravascular units. CEU will likely provide important insight into the pathophysiology of worsening vaso-occlusive events during crisis and may also potentially be used to assess the efficacy of new treatments for SCD. Disclosures:No relevant conflicts of interest to declare.

Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a diseases that alters human placenta macro and microvascular reactivity as a result of endothelial dysfunction. The human placenta is a highly vascularized organ which lacks innervation, so blood flux is governed by locally released vasoactive molecules, including the endogenous nucleoside adenosine and the free radical nitric oxide (NO). Altered adenosine metabolism and uptake by the endothelium leads to increased NO synthesis which then turns-off the expression of genes coding for a family of nucleoside membrane transporters belonging to equilibrative nucleoside transporters, particularly isoforms 1 (hENT1) and 2 (hENT2). This mechanism leads to increased extracellular adenosine and, as a consequence, activation of adenosine receptors to further sustain a tonic activation of NO synthesis. This is a phenomenon that seems operative in the placental macro and microvascular endothelium in GDM. We here summarize the findings available in the literature regarding these mechanisms in the human feto-placental circulation. This phenomenon is altered in the feto-placental vasculature, which could be crucial for understanding GDM deleterious effects in fetal growth and development.

Multiple-Capillary Measurement of RBC Speed, Flux, and Density with Optical Coherence Tomography

As capillaries exhibit heterogeneous and fluctuating dynamics even during baseline, a technique measuring red blood cell (RBC) speed and flux over many capillaries at the same time is needed. Here, we report that optical coherence tomography can capture individual RBC passage simultaneously over many capillaries located at different depths. Further, we demonstrate the ability to quantify RBC speed, flux, and linear density. This technique will provide a means to monitor microvascular flow dynamics over many capillaries at different depths at the same time.

Proceso de atención de Enfermería, a una adolescente con dependencia en la necesidad de oxigenación por ventrículo único

Persons with a single ventricle face several limitations and require specialized nursing care. This problem is characterized by a right left cardiac blood flux shortcut which leads to hypoxia. In these cases, a special professional competence is required in order to provide quality of care. Any nursing intervention should be ethically oriented towards the patient, family, and community. The objective of this article is to show the Nursing Assisting Process in a teenager with oxygen-needs alterations. The theoretical model was based on the 14 needs proposed by Virginia Henderson. A specific instrument was used. From the obtained data, two major diagnoses were established, and specific care interventions were planned and assessed. The patient did not show major signs of hemodynamic unbalances however, due to the complexity of the pathology, it was not possible to reduce the patient ́s level of oxygen dependence.

Simultaneous measurement of microvascular blood flux and tissue oxygenation in human skin

We have measured skin microvascular blood flux (PU) and microvascular oxygenation (SO2,%) simultaneously, using a combined OXY+flow+temperature probe (moorCP2T‐2000 probe with the moorVMS‐LDF and moorVMS‐OXY). Parameters were measured at the forearm in healthy participants at rest and during post‐occlusive reactive hyperaemia (PORH) (180 mmHg for 3 min) and local tissue warming (43oC for 20 min). The relationship between simultaneously measured flux and SO2 was best fitted by a decaying exponential with R2 = 0.744. There was also coherence between low frequency oscillations in resting flux and SO2 across the endothelial (0.64(0.12)) and neurogenic (0.60(0.12)) power spectral density bands (mean(SD)). These data demonstrate an association between a simultaneous measure of microvascular blood flux and microvascular oxygenation. Further, our data confirm that spontaneously occurring low frequency oscillations associated with flow motion are present in a measure of microvascular oxygenation and are closely associated with those in the simultaneously measured blood flux.Supported by the EPSRC and Diabetes UK

Low‐dose intra‐nasal cocaine causes subclinical microvascular coronary ischemia in humans

We used myocardial contrast echocardiography (MCE) to test the hypothesis that cocaine, an indirect sympathomimetic, causes microvascular ischemia in the human heart. Measurements were performed at baseline and after low‐dose, non‐intoxicating, intranasal cocaine (2 mg/kg) in 10 healthy cocaine‐naïve men (median age 32 yrs). Destruction‐refill data on MCE were fit to the equation: y = A(1‐e− βt) to quantify functional capillary blood volume (A), flux rate (β) and myocardial blood flow (MBF) (Product of A and β). Heart rate (HR), mean arterial pressure (MAP), and left ventricular (LV) work (end‐systolic elastance × HR) were measured. Validation experiments included with‐in day reproducibility, control experiments using low‐dose dobutamine, and cross‐modality experiments comparing MCE with first‐pass magnetic resonance perfusion imaging. Cocaine caused a rise (p&lt;.05) in MAP (+14±2 mmHg), HR (+8±3 bpm), and LV work (+50±18%). Despite this significant rise in oxygen demand, MBF declined significantly (103.7±9.8 to 75.9±10.8 a.u.) due mainly to reductions in capillary blood volume (133.9±5.1 to 111.7±7.7 a.u., p&lt;.05) with no change in feed artery flow velocity (0.8±0.1 to 0.7±0.1 a.u.). We conclude that cocaine‐induced sympathoexcitation acts at the level of the coronary microvessels, to cause a mismatch between myocardial oxygen demand and MBF.

Quantification of microvascular cerebral blood flux and late‐stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI

Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size < 3 mm) when compared with healthy tissue. At a late developmental stage (tumor size > 3 mm), we observed a significant decrease in the cerebral blood flux inside the gliosarcoma (-33%, p < 0.01) and compartmentalization of the tumor (p < 0.05). FENSI flux maps delineated a low-flux tumor core (58 ± 17 μL/min/cm(2) ) and higher vascularized regions around the tumor periphery (85 ± 21 μL/min/cm(2) ). Histology was performed on 11 animals to finely probe the intratumor heterogeneity and microvessel density, and the results were compared with the information derived from FENSI flux maps. The hyper- and hypoperfused tumor regions revealed with FENSI at the late tumor developmental stage correlated well with the ratios of high and low blood vessel density (R(2) = 0.41) and fractional vascular surface (R(2) = 0.67) observed with fluorescence microscopy [cluster of differentiation 31 (CD31) staining].

Gestational Diabetes Mellitus and the Role of Adenosine in the Human Placental Endothelium and Central Nervous System

Diabetes mellitus is a syndrome that alters macro and microvascular reactivity as a result of endothelial dysfunction. This phenomenon occurs in vascular beds from different regions in the adult human body, as well as the developing fetus including the placenta and the brain vasculature. The human placenta is highly vascularized lacking of innervation, so that blood flux is governed by locally released vasoactive moleculles, including the endogenous nucleoside adenosine and the gas nitric oxide (NO). Altered adenosine uptake by the endothelium leads to increased synthesis of NO resulting in repression of equilibrative nucleoside membrane transporters isoforms 1 (hENT1) and 2 (hENT2). The latter result in higher extracellular adenosine and activation of adenosine receptors (ARs) sustaining tonic activation of NO synthesis in gestational diabetes mellitus (GDM). Similar alterations are apparent in the fetus brain. Because GDM associates with serious alterations in the CNS functions leading to abnormal higher cognitive functions, among others complications, it is proposed that altered adenosine metabolism, uptake and dynamics of ARs activation in the brain is a factor leading to these pathologies. We here summarize the findings available in the literature regarding these mechanisms in the human fetus brain with reference to that in the feto-placental circulation. We emphasize the possibility that adenosine plays a key role in the functional link established by astrocytes connecting neurons and the brain vasculature. This phenomenon is altered in the brain and the feto-placental vasculature, which could be crucial for understanding GDM deleterous effects in fetal growth and development, as well as CNS abnormal function in adulthood.

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.

Lattice Boltzmann Simulation of Effect of Rolling Manipulation of Traditional Chinese Massage on Blood Flow

A 2D Lattice Boltzmann model for a blood vesssel under rolling manipulation(RM) was presented. The influence of rolling frequency and stenosis coefficient on blood flux, wall shear stress and flow velocity was given by the numerical simulation based on lattice Boltzmann method . It is found that increasing RM frequency can not always increase the flux. There is a proper RM frequency for maximum flux.When the maximum stenosis coefficient increases,the change range of flux and wall shear stress will increase. The rolling massage can also change flow velocity in different sections of blood vessel.

Involvement of cytochrome epoxygenase metabolites in cutaneous postocclusive hyperemia in humans

Several mediators contribute to postocclusive reactive hyperemia (PORH) of the skin, including sensory nerves and endothelium-derived hyperpolarizing factors. The main objective of our study was to investigate the specific contribution of epoxyeicosatrienoic acids in human skin PORH. Eight healthy volunteers were enrolled in two placebo-controlled experiments. In the first experiment we studied the separate and combined effects of 6.5 mM fluconazole, infused through microdialysis fibers, and lidocaine/prilocaine cream on skin PORH following 5 min arterial occlusion. In the second experiment we studied the separate and combined effects of 6.5 mM fluconazole and 10 mM N(G)-monomethyl-l-arginine (l-NMMA). Skin blood flux was recorded using two-dimensional laser speckle contrast imaging. Maximal cutaneous vascular conductance (CVC(max)) was obtained following 29 mM sodium nitroprusside perfusion. The PORH peak at the placebo site averaged 66 ± 11%CVC(max). Compared with the placebo site, the peak was significantly lower at the fluconazole (47 ± 10%CVC(max); P < 0.001), lidocaine (29 ± 10%CVC(max); P < 0.001), and fluconazole + lidocaine (30 ± 10%CVC(max); P < 0.001) sites. The effect of fluconazole on the area under the curve was more pronounced. In the second experiment, the PORH peak was significantly lower at the fluconazole site, but not at the l-NMMA or combination site, compared with the placebo site. In addition to sensory nerves cytochrome epoxygenase metabolites, putatively epoxyeicosatrienoic acids, play a major role in healthy skin PORH, their role being more important in the time course rather than the peak.

Increasing acclimation period improves the reproducibility of short-heating local thermal hyperemia

ObjectivesThe axon reflex (AR) can be induced by the activation of afferent C-fibers during local skin heating. The previously used long-heating local thermal hyperemia (LTH) protocols tested AR flare by normalizing to endothelial-mediated maximal vasodilatation to adjust capillary heterogeneity when the recording sites were randomly selected. The AR flare induced by short local heating can be reproducible without using the data from subsequent longer heating for normalization when the recording sites were fixed with holders in the same session. The aim of this study was to investigate the effect of acclimation period on the intersession reproducibility of short-heating LTH when the recording sites were relocated after a longer interval of 1–3days. MethodsAfter 30 or 60min acclimation, LTH with 5min heating was assessed on bilateral human forearms using single-point laser Doppler flowmetry. The test was repeated at the same recording sites again at the same time 1–3days later. Baseline and heating blood flux were analyzed and the data were expressed as different forms. Reproducibility of two tests was assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC) statistics. ResultsThe intersession reproducibility of peak cutaneous vascular conductance (CVC) (CV=18.38%, ICC=0.82), peak CVC change (CV=20.38%, ICC=0.83) and 4min area-under-the-curve (AUC) (CV=18.66%, ICC=0.75) of the right forearm and time to peak (CV=16.84%, ICC=0.52) of the left forearm were acceptable after 30min acclimation. When the acclimation period was increased to 60min, all of these data except 4min AUC of both sides reached an acceptable level. ConclusionsThe AR flare induced by short local heating is reproducible when the recording sites are relocated by a predefined rule. The reproducibility of LTH on right forearm is different from that on left forearm, and increasing acclimation period improves the reproducibility.

Peripheral vascular response to inspiratory breath hold in paediatric homozygous sickle cell disease

New Findings• What is the central question of this study?Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS- mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger-tip cutaneous micovasculature.• What is the main finding and its importance?We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG.This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.There is increasing evidence that autonomic dysfunction in adults with homozygous sickle cell (haemoglobin SS) disease is associated with enhanced autonomic nervous system-mediated control of microvascular perfusion. However, it is unclear whether such differences are detectable in children with SS disease. We studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range 5.1–10.6) years] and 20 control children without symptoms of SS disease [8 boys; 8.7 (5.5–10.8) years] and recorded mean arterial blood pressure (ABP) and daytime haemoglobin oxygen saturation (). Cutaneous blood flux at rest (RBF) and during the sympathetically activated vasoconstrictor response to inspiratory breath hold (IBH) were measured in the finger pulp of the non-dominant hand using laser Doppler fluximetry. Local factors mediating flow motion were assessed by power spectral density analysis of the oscillatory components of the laser Doppler signal. The RBF measured across the two study groups was negatively associated with age (r=−0.25, P < 0.0001), ABP (r=−0.27, P= 0.02) and daytime (r=−0.30, P= 0.005). Children with SS disease had a higher RBF (P= 0.005) and enhanced vasoconstrictor response to IBH (P= 0.002) compared with control children. In children with SS disease, higher RBF was associated with an increase in the sympathetic interval (r=−0.28, P= 0.022). The SS disease status, daytime and age explained 22% of the variance in vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood flow and blood flow responses in the skin of young African children with SS disease differ from those of healthy control children, with increased resting peripheral blood flow and increased sympathetic stimulation from a young age in SS disease. They further suggest that the laser Doppler flowmetry technique with inspiratory breath hold manoeuvre appears to be robust for use in young children with SS disease, to explore interactions between , ABP and autonomic function with clinical complications, e.g. skin ulceration.

Role of specific T-type calcium channel blocker R(−) efonidipine in the regulation of renal medullary circulation

Blockade of the T-type calcium channel (TCC), which is expressed in the renal efferent arterioles of the juxtamedullary nephron and vasa recta, has been shown to protect against renal injury. Studies were designed to determine the effects of a specific TCC blocker, R(-) efonidipine [R(-)EFO], on the regulation of renal circulation. Renal medullary blood flux (MBF) and cortical blood flux (CBF) were simultaneously monitored using laser-Doppler flowmetry in Sprague-Dawley rats. Responses were also determined in rats with angiotensin II (AngII) induced renal ischemia. Intravenous (i.v.) or renal interstitial (r.i.) infusion of R(-)EFO (0.25 mg/h, i.v. or r.i.) significantly increased MBF by 24.0 ± 7.0 and 21.0 ± 4.4%, respectively, but without changing CBF or mean arterial pressure. The nitric oxide (NO) synthase inhibitor NG-nitro-L-argininemethylester (L-NAME, 1 μg/kg per min, i.v. or r.i.) significantly attenuated R(-)EFO-induced increase in MBF. R(-)EFO inhibited the AngII-mediated (50 ng/kg per min, i.v.) reduction of MBF (28.4 ± 1.7%), which was associated with increased urinary NO(2) + NO(3) excretion and decreased urinary hydrogen peroxide (H(2)O(2)) excretion. Intracellular H(2)O(2) fluorescence (real-time fluorescence imaging) in the epithelial cells of isolated medullary thick ascending limb (mTAL) significantly increased following AngII stimulation (1 μmol/L, 235 ± 52 units), which was significantly inhibited by pre and coincubation with R(-)EFO. R(-)EFO stimulation also increased the intracellular NO concentration in the epithelial cells of mTAL (220 ± 62 units). These results suggest that TCC blockade with R(-)EFO selectively increases MBF, an effect that appears to be mediated by changes in renal NO and oxidative stress balance, which may protect against ischemic renal injury in the renal medullary region.