Comparison of laser speckle contrast imaging with laser Doppler for assessing microvascular function

Objective: To compare the inter-day reproducibility of post-occlusive reactive hyperaemia (PORH) and sympathetic vasomotor reflexes assessed by single-point laser Doppler flowmetry (SP-LDF), integrating-probe LDF (IP-LDF) and laser speckle contrast imaging (LSCI), and the spatial variability of PORH assessed by IP-LDF and LSCI. We also evaluated the relationship between IP-LDF and LSCI perfusion values across a broad range of skin blood flows. Methods: Eighteen healthy adults (50% male, age 27 ± 4 years) participated in this study. Using SP-LDF, IP-LDF and LSCI, an index of skin blood flow was measured on the forearm during PORH (1-, 5- and 10-min occlusions) and on the finger pad during inspiratory gasp and cold pressor tests. These tests were repeated 3-7 days later. Data were converted to cutaneous vascular conductance (CVC; laser Doppler flow/mean arterial pressure) and expressed as absolute and relative changes from pre-stimulus CVC (ΔCVCABS and ΔCVCREL, respectively), as well as normalised to peak CVC for the PORH tests. Reproducibility was expressed as within-subjects coefficients of variation (CV, in %) and intraclass correlation coefficients. Results: The reproducibility of PORH on the forearm was poorer when assessed with SP-LDF and IP-LDF compared to LSCI (e.g., CV for 5-min PORH ΔCVCABS = 35, 27 and 19%, respectively), with no superior method of data expression. In contrast, the reproducibility of the inspiratory gasp and cold pressor test responses on the finger pad were better with SP-LDF and IP-LDF compared to LSCI (e.g., CV for inspiratory gasp ΔCVCREL = 13, 7 and 19%, respectively). The spatial variability of PORH responses was poorer with IP-LDF compared to LSCI (e.g., CV ranging 11-35% versus 3-16%, respectively). The association between simultaneous LSCI and IP-LDF perfusion values was non-linear. Conclusion: The reproducibility of cutaneous PORH was better when assessed with LSCI compared to SP-LDF and IP-LDF; probably due to measuring larger skin areas (lower inter-site variability). However, when measuring sympathetic vasomotor reflexes on the finger pad, reproducibility was better with SP-LDF and IP-LDF, perhaps due to the high sensitivity of LSCI to changes in skin blood flow at low levels

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Neuropeptide Y and neurovascular control in skeletal muscle and skin.

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered

WISE-2005: prolongation of left ventricular pre-ejection period with 56 days head-down bed rest in women

This study tested the hypothesis that prolonged physical deconditioning affects the coupling of left ventricular depolarization to its ejection (the pre-ejection period, PEPi) and that this effect is minimized by exercise countermeasures. Following assignment to non-exercise (Control) and exercise groups (Exercise), 14 females performed 56 days of continuous head-down tilt bed rest. Measurements of the electrocardiogram (ECG) and stroke volume (Doppler ultrasound) during supine rest were obtained at baseline prior to (Pre) and after (Post) the head-down tilt bed rest (HDBR) period. Compared with Pre, the PEPi was increased following head-down tilt bed rest (main effect, P \u3c 0.005). This effect was most dominant in the Control group [Pre = 0.038 ± 0.06 s (s.d.) versus Post = 0.054 ± 0.011 s; P \u3c 0.001]. In the Exercise group, PEPi was 0.032 ± 0.005 s Pre and 0.038 ± 0.018 s Post; P= 0.08. Neither the QRS interval nor cardiac afterload was modified by head-down tilt bed rest in Control or Exercise groups. Low-dose isoprenaline infusion reversed the head-down tilt bed rest-induced delay in the PEPi. These results suggest that head-down tilt bed rest leads to a delayed onset of systolic ejection following left ventricular depolarization in a manner that is affected little by the exercise countermeasure but is related to Β-adrenergic pathways. The delayed onset of systole following head-down tilt bed rest appears to be related to mechanism(s) affecting contraction of the left ventricle rather than its depolarization. © 2010 The Authors. Journal compilation © 2010 The Physiological Society

Baseline Surface Radiation Network (BSRN): structure and data description (1992–2017)

Small changes in the radiation budget at the earth's surface can lead to large climatological responses when persistent over time. With the increasing debate on anthropogenic influences on climatic processes during the 1980s the need for accurate radiometric measurements with higher temporal resolution was identified, and it was determined that the existing measurement networks did not have the resolution or accuracy required to meet this need. In 1988 the WMO therefore proposed the establishment of a new international Baseline Surface Radiation Network (BSRN), which should collect and centrally archive high-quality ground-based radiation measurements in 1 min resolution. BSRN began its work in 1992 with 9 stations; currently (status 2018-01-01), the network comprises 59 stations (delivering data to the archive) and 9 candidates (stations recently accepted into the network with data forthcoming to the archive) distributed over all continents and oceanic environments. The BSRN database is the World Radiation Monitoring Center (WRMC). It is hosted at the Alfred Wegener Institute (AWI) in Bremerhaven, Germany, and now offers more than 10 300 months of data from the years 1992 to 2017. All data are available at https://doi.org/10.1594/PANGAEA.880000 free of charge

Comparison of different wheelchair seating on thermoregulation and perceptual responses in thermoneutral and hot conditions in children

We examined the effects of 4 different wheelchair seatings on physiological and perceptual measures in 21 healthy, pre-pubertal children (9 ± 2 years). Participants were able-bodied and did not regularly use a wheelchair. Participants sat for 2 h in Neutral (∼22.5 °C, ∼40%RH) and Hot (∼35 °C, ∼37%RH) conditions. Four seating technologies were: standard incontinent cover and cushion (SEAT1); standard incontinent cover with new cushion (SEAT2) were tested in Neutral and Hot; new non-incontinent cover with new cushion (SEAT3); new incontinent cover and new cushion (SEAT4) were tested in Neutral only. Measurements included skin blood flow (SkBF), sweating rate (SR) and leg skin temperature (TlegB) on the bottom of the leg (i.e. skin-seat interface), heart rate (HR), mean skin temperature, tympanic temperature, thermal comfort, and thermal sensation. During Neutral, SkBF and TlegB were lower (∼50% and ∼1 °C, respectively) and SR higher (∼0.5 mg cm−2·min−1) (p  0.05). During Hot, HR and temperatures were higher than in Neutral but there were no differences (p > 0.05) between SEATs. New cover and cushion improved thermoregulatory responses during Neutral but not Hot. An impermeable incontinent cover negated improvements from cushion design. Seat cover appears more important than seat cushion during typical room conditions

Voluntary Exercise Reduces Alzheimer’s-like Pathology After Inflammation in Mice

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has previously shown that 7 consecutive peripheral injections of a bacterial mimetic led to systemic inflammation, increased levels of Ab in the brain, and cognitive dysfunction (Kahn et al., 2012; Weintraub et al., 2013). Currently there are very few effective treatments that diminish AD symptomology. One documented way to decrease inflammation without the use of pharmaceuticals is through regular physical exercise (Cho et al., 2003; Cotman & Berchtold, 2002; Cotman et al., 2007). The present study tested the hypothesis that voluntary exercise would decrease the level of brain Ab following inflammation. Interestingly, we found that two weeks of voluntary wheel running after inflammation led to a reduction of Ab when compared to sedentary recovery. These results indicate that exercise may be an effective modality to reduce AD-like pathology, and that these effects appear to be facilitated by higher versus lower levels of exercise, as measured by total distance run

Skin blood flow responses to acetylcholine and local heating at rest and 60%V O2max, and associated nitric oxide contribution, in boys vs. girl

To determine sex-related differences in the skin-blood-flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children. Additionally, the contribution of nitric oxide (NO) was examined. Methods: Forearm SkBF during local heating (44˚C), ACh iontophoresis, and exercise (30 min cycling, 60% OV 2max) was assessed, using Laser-Doppler fluxmetry, in 12 boys and 12 girls (7–13 yrs old), with and without NO synthase inhibition, using Nω-nitro-L-arginine methyl ester (L-NAME) iontophoresis. Results: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (Local heating: 1445±900% and 1432±582% of baseline, , p=.57; ACh: 673±434% and 558±405% of baseline, respectively, p=0.18). Exercise-induced increase in SkBF was greater in boys than girls (528±290 and 374±192% of baseline, respectively, p=0.03). L-NAME blunted the SkBF response to ACh and during exercise (p<0.001), with no difference between sexes. Summary: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of NO was not different between boys and girls. It is suggested that the greater SkBF response in the boys during exercise is related to greater relative heat production and dissipation needs during this exercise intensity. The response to body-size-related workload should be further examined

Increased Blood Pressure and Hyperdynamic Cardiovascular Responses in Carriers of a Common Hyperfunctional Variant of Adenylyl Cyclase 6

ABSTRACT Adenylyl cyclase (ADCY) is a critical regulator of metabolic and cardiovascular function. We have identified a genetic variant (A674S) in ADCY isoform 6 (ADCY6). Subsequent studies demonstrated that the expression of this ADCY6 variant paralleled an increase in adenylyl cyclase-mediated functions. However, the impact of this hyperfunctional variant on cardiovascular function is unknown. Therefore, we evaluated the hemodynamic profile of carriers of ADCY6 A674S. The association of ADCY6 A674S with anthropometric and hemodynamic parameters was assessed in 364 healthy white subjects. The allele encoding this variant was present in 6.9% of the subjects, and those individuals had increased blood pressure. To determine the hemodynamic basis for increased blood pressure in carriers of ADCY6 A674S, we assessed forearm blood flow (FBF) and cardiac output at rest, during handgrip exercise (to test vasodilator responsiveness), and with lower body negative pressure [to test forearm vasoconstrictor and heart rate (HR) responsiveness] in a subsample of 21 subjects. At rest, cardiac output and blood pressure were higher in carriers of ADCY6 A674S. This was paralleled by an increase in plasma renin activity, but not in plasma norepinephrine. During handgrip exercise, FBF and vasodilator responses were greater in carriers of ADCY6 A674S. Responses to reactive hyperemia were not different between genotypes. With lower body negative pressure, the HR response to this orthostatic stress was markedly higher in carriers of ADCY6 A674S. These data indicate that the relatively common hyperfunctional ADCY6 A674S variant underlies a hyperdynamic cardiovascular response and increased blood pressure

Re-examining the consumption-wealth relationship : the role of model uncertainty

This paper discusses the consumption-wealth relationship. Following the recent influential workof Lettau and Ludvigson [e.g. Lettau and Ludvigson (2001), (2004)], we use data on consumption, assets andlabor income and a vector error correction framework. Key …ndings of their work are that consumption doesrespond to permanent changes in wealth in the expected manner, but that most changes in wealth are transitoryand have no e¤ect on consumption. We investigate the robustness of these results to model uncertainty andargue for the use of Bayesian model averaging. We …nd that there is model uncertainty with regards to thenumber of cointegrating vectors, the form of deterministic components, lag length and whether the cointegratingresiduals a¤ect consumption and income directly. Whether this uncertainty has important empirical implicationsdepends on the researcher's attitude towards the economic theory used by Lettau and Ludvigson. If we workwith their model, our findings are very similar to theirs. However, if we work with a broader set of models andlet the data speak, we obtain somewhat di¤erent results. In the latter case, we …nd that the exact magnitudeof the role of permanent shocks is hard to estimate precisely. Thus, although some support exists for the viewthat their role is small, we cannot rule out the possibility that they have a substantive role to play