Peripheral Vascular Function Research Articles

The acute and postprandial effects of sugar moiety on vascular and metabolic health outcomes in adolescents.

This study explored the cardiometabolic responses to sugar moieties acutely, and following a subsequent mixed meal tolerance test (MMTT). Twenty-one healthy adolescents (N= 10 female, 14.3± 0.4 years) completed 3 experimental and 1 control condition, in a counterbalanced order. These consisted of different drinks to compare the effect of 300mL of water (control), or 300mL of water mixed with 60g of glucose, fructose or sucrose, on vascular function (flow-mediated dilation (FMD), microvascular reactivity (total hyperaemic response; TRH), and cerebrovascular reactivity (CVR)), and blood samples for uric acid, glucose, triglycerides and lactate concentrations. FMD increased 1h after glucose and sucrose (P< 0.001, ES≥ 0.92) but was unchanged following fructose and water (P≥ 0.19, ES≥ 0.09). CVR and TRH were unchanged 1h following all conditions (P> 0.57, effect size (ES)> 0.02). Following the MMTT, FMD was impaired in all conditions (P< 0.001, ES> 0.40) with no differences between conditions (P> 0.13, ES< 0.39). Microvascular TRH was increased in all conditions (P= 0.001, ES= 0.88), and CVR was preserved in all conditions after MMTT (P= 0.87, ES= 0.02). Blood uric acid concentration was elevated following fructose consumption and the MMTT (P< 0.01, ES> 0.40). Consumption of a sugar sweetened beverage did not result in vascular dysfunction in healthy adolescents; however, the vascular and metabolic responses were dependent on sugar moiety. Novelty: Glucose consumption acutely increases peripheral vascular function in healthy adolescents. Acute sugar sweetened beverage consumption (sucrose) does not result in adverse vascular outcomes. Elevations in uric acid are observed with fructose consumption, which may have implications over repeated exposure.

Neurobiological Pathways Linking Acute Mental Stress to Impairments in Executive Function in Individuals with Coronary Artery Disease.

Background:Individuals with coronary artery disease (CAD) have worse executive function compared to the general population but the mechanisms are unknown.Objective:To investigate the role of acute mental stress (MS) on the executive function of patients with CAD.Methods:Participants with stable CAD underwent acute MS testing with simultaneous peripheral vascular function measurements and brain imaging using high resolution-positron emission tomography. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during MS/baseline was calculated as a measure of microvascular constriction during MS. Plasma levels of catecholamine and interleukin-6 were assessed at baseline and after MS. Executive function was assessed both at baseline and at 2 years follow-up using the Trail Making Test parts A and B.Results:We studied 389 individuals with brain data available for 148 participants. Of this population follow-up cognitive assessments were performed in 226 individuals (121 with brain imaging). After multivariable adjustment for baseline demographics, risk factors, and medication use, a lower sPAT, indicating greater vasoconstriction, a higher inferior frontal lobe activation with MS, and increases in norepinephrine and IL-6 levels with MS were all independently associated with greater time to complete Trail B test.-38.4ptConclusion:In response to acute MS, greater peripheral vasoconstriction, higher inferior frontal lobe brain activation, and increases in the levels of norepinephrine and IL-6 are associated with worse executive function.

Can exercise training enhance the repeated remote ischaemic preconditioning stimulus on peripheral and cerebrovascular function in high-risk individuals?

BackgroundRepeated exposure to remote ischaemic preconditioning (rIPC; short bouts of non-lethal ischaemia) enhances peripheral vascular function within 1 week; whereas, longer periods of rIPC (~ 1 year) may improve cerebral perfusion. Increasing the ‘dose’ of rIPC may lead to superior effects. Given the similarities between exercise and rIPC, we examined whether adding exercise to the rIPC stimulus leads to greater adaptation in systemic vascular function.MethodsNineteen individuals with increased risk for cardiovascular disease (CVD) were randomly allocated to either 8 weeks of rIPC (n = 9) or 8 weeks of rIPC + exercise (rIPC + Ex) (n = 10). rIPC was applied three times per week in both conditions, and exercise consisted of 50 min (70% heart rate max) of cycling 3 times per week. Peripheral endothelial function was assessed using flow-mediated dilation (FMD) before and after ischaemia–reperfusion (IR). Cerebrovascular function was assessed by dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR), and cardio-respiratory fitness (VO2peak) using a maximal aerobic capacity test.ResultsFMD% increased by 1.6% (95% CI, 0.4, 2.8) following rIPC + Ex and by 0.3% (− 1.1, 1.5) in the only rIPC but this did not reach statistical significance (P = 0.65). Neither intervention evoked a change in dCA or in CVR (P > 0.05). VO2peak increased by 2.8 ml/kg/min (1.7, 3.9) following the rIPC + Ex and by 0.1 ml/kg/min (− 1.0, 1.4) following the rIPC only intervention (P = 0.69).ConclusionCombining exercise with rIPC across an 8-week intervention does not lead to superior effects in cerebrovascular and peripheral vascular function compared to a repeated rIPC intervention in individuals at risk of CVD.

Non-Invasive Assessment of Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterised by an increased pressure in the pulmonary arterial circulation, resulting in the elevation of pulmonary vascular resistance. Pulmonary endothelial dysfunction and inflammation, triggered by shear stress and hypoxia, constitute the hallmarks of pulmonary vasculopathy by promoting endothelial and smooth muscle cells proliferation, vasoconstriction, and thrombosis. While research was predominantly focused on pulmonary vasculature, the investigation of peripheral endothelial damage in different vascular beds has attracted the interest over the last years. As a result, effective non-invasive methods that can assess the endothelial function and the architectural integrity have been utilized for the evaluation of pulmonary and peripheral vasculature. Non-invasive plethysmography, pulmonary flow reserve, nailfold videocapillaroscopy, near-infrared spectroscopy, and imaging techniques such as magnetic resonance angiography and perfusion imaging coupled by a number of biomarkers can be used for the assessment of peripheral vascular function in PAH individuals. In this review, we summarise and critically approach the current evidence of more systemic derangement of vascular function in PAH defined by novel, non-invasive methods employed for functional and morphological assessment of endothelium and microcirculation.

Comprehensive assessment of cardiovascular structure and function and disease risk in middle-aged ultra-endurance athletes

Background and aimsRecent studies suggest that long-term endurance training may be damaging to the heart, thus increasing cardiovascular disease (CVD) risk. However, studies utilizing cardiac imaging are conflicting and lack measures of central and peripheral vascular structure and function, which are also independently predictive of CVD events. MethodsWe performed a comprehensive assessment of cardiovascular structure and function in long-term (≥ 10 years) ultra-endurance athletes (ATH, 14 M/11 F, 50 ± 1 y) and physically active controls (CON, 9 M/9 F, 49 ± 2 y). ResultsAs expected, left ventricular mass and end-diastolic volume (echocardiography) were greater in ATH vs CON, whereas there was no difference in cardiac function at rest. Coronary artery calcium scores (computed tomography) were not statistically different between groups. There was no evidence of myocardial fibrosis (contrast magnetic resonance imaging) in any subject. Aortic stiffness (carotid-femoral pulse wave velocity) was lower in ATH vs CON (6.2 ± 0.2 vs 6.9 ± 0.2 m/s, p < 0.05), whereas carotid intima-media thickness (ultrasound) was not different between groups. Peripheral vascular endothelial function (flow-mediated vasodilation of the brachial artery) and microvascular function (peak blood velocity) in response to 5 min of forearm ischemia were not different between groups. Furthermore, there was no difference in 10-year coronary heart disease risk (ATH; 2.3 ± 0.5 vs CON; 1.6 ± 0.2%, p > 0.05). ConclusionsOur data indicate that middle-aged ultra-endurance ATH do not have marked signs of widespread cardiovascular dysfunction or elevated CHD risk compared to CON meeting physical activity guidelines.

The Effect of Exercise During Pregnancy on Maternal and Offspring Vascular Outcomes: a Pilot Study

The aim of this pilot study is to obtain estimates for the change in maternal cerebrovascular (primary) and offspring vascular structure (secondary) during healthy pregnancy that includes structured exercise. Eighteen pregnant women self-assigned to a moderate-intensity aerobic exercise intervention or a control group. Maternal cerebral blood flow (CBF) at the middle cerebral artery, cerebro- and peripheral-vascular function was assessed at the end of each trimester. Offspring carotid artery intima-media thickness (IMT) was measured within 12 weeks of birth. For exploratory purposes, we performed statistical analysis to provide estimates of the change for primary and secondary outcome variables. Maternal CBF reduced (− 8 cm s−1 [− 14 to − 2]) with evidence of change to cerebral autoregulation (normalised gain: 0.12 %cm s−1% mmHg−1mmHg/% [− 0.18 to 0.40]) during pregnancy. Offspring carotid IMT was smaller in the exercise group (− 0.04 mm [− 0.12–0.03]) compared with controls. Based upon this data, a sample size of 33 and 57 in each group is required for low-frequency normalised gain and offspring IMT, respectively. This would provide 90% power to detect statistically significant (P < 0.05) between group differences in a randomised controlled trial. CBF is reduced in pregnancy, possibly due to reduced vascular resistance and altered maternal cerebral autoregulation. Maternal exercise had negligible effects on cerebrovascular adaptation to pregnancy, but we observed lower offspring carotid artery wall thickness following maternal exercise. Our directional findings and sample size estimations should be explored in a fully powered randomised control trial.Clinical trial registration: The trial was registered on March 14th at https://register.clinicaltrials.gov (NCT03079258). Participant enrolment began on 3rd April 2016.

Hourly staircase sprinting exercise "snacks" improve femoral artery shear patterns but not flow-mediated dilation or cerebrovascular regulation: a pilot study.

Healthy males (n = 10; age: 24 ± 4 years; body mass index: 24 ± 2 kg·m-2) completed 2 randomized conditions separated by ≥48 h involving 6-8.5 h of sitting with ("stair snacks") and without (sedentary) hourly staircase sprint interval exercise (∼14-20 s each). Resting blood flow and shear rates were measured in the femoral artery, internal carotid artery, and vertebral artery (Duplex ultrasound). Flow-mediated dilation (FMD) was quantified as an index of peripheral endothelial function in the femoral artery. Neurovascular coupling (NVC; regional blood flow response to local increases in cerebral metabolism) was assessed in the posterior cerebral artery (transcranial Doppler ultrasound). Femoral artery hemodynamics were higher following the active trial with no change in the sedentary trial, including blood flow (+32 ± 23% vs. -10 ± 28%; P = 0.015 and P = 0.253, respectively), vascular conductance (+32 ± 27% vs. -15 ± 26%; P = 0.012 and P = 0.098, respectively), and mean shear rate (+17 ± 8% vs. -8 ± 28%; P = 0.004 and P = 0.310, respectively). The change in FMD was not different within or between conditions (P = 0.184). Global cerebral blood flow (CBF), conductance, shear patterns, and NVC were not different within or between conditions (all P > 0.05). Overall, exercise "stair snacks" improve femoral artery blood flow and shear patterns but not peripheral (e.g., FMD) or cerebral (e.g., CBF and NVC) vascular function following prolonged sitting. The study was registered at ClinicalTrials.gov (NCT03374436). Novelty: Breaking up 8.5 h of sitting with hourly staircase sprinting exercise "snacks" improves resting femoral artery shear patterns but not FMD. Cerebral blood flow and neurovascular coupling were unaltered following 6 h of sitting with and without hourly exercise breaks.

Influence of hormonal contraceptives on peripheral vascular function and structure in premenopausal females: a review.

Hormonal contraceptives are one of the most widely used prescriptions for premenopausal women worldwide. Although the risk of venous and arterial cardiovascular events (e.g., deep vein thrombosis, arterial clotting) with hormonal contraceptives, specifically oral contraceptive pills, has been established, the literature on early risk indicators, such as peripheral vascular structure and function has yet to be consolidated. The purpose of this review is to summarize literature examining the impact of different hormonal contraceptives on vascular function and structure, including consideration of phasic differences within a contraceptive cycle, and to propose future directions for research. It is evident that hormonal contraceptive use appears to impact both macrovascular and microvascular endothelial function, with phasic differences in some contraceptive types dependent on progestin type, the ratio of ethinyl estradiol-to-progestin, and route of administration. However, hormonal contraceptives do not appear to impact smooth muscle function in the macrovasculature or microvasculature, arterial stiffness, or vascular structure. Underlying mechanisms for observed impacts and areas of future research are discussed. This review provides timely consolidation of research examining hormonal contraceptives and peripheral vascular function and structure and provides guidance on considerations for hormonal contraceptive use in study design.

Age alters peripheral vascular endothelial function without affecting coronary flow reserve in healthy volunteers

Abstract Background Age is a key risk factor contributing to vascular endothelial dysfunction. Whether the impact of ageing is uniform on various vascular beds is unknown. Endothelial function is classically evaluated by the brachial flow mediated dilatation (FMD) after a brief occlusion which mainly involves nitric oxide (NO) production. However, FMD measurement, requiring highly trained technicians, has been shown to be associated with a high degree of variability. Endothelial function could be also assessed by cutaneous iontophoresis combined with Laser Doppler. By contrast to FMD, this method is easily done by nurses and shows less variability. In parallel, myocardial imaging allows measurement of coronary flow reserve (CFR) coupled with an adenosine challenge leading to both a NO release and a modulation of potassium channels. Purpose The aim of this study was to determine the impact of ageing on vasodilation of peripheral (cutaneous) and coronary blood vessels in healthy volunteers. Methods This prospective single German center study enrolled 75 healthy non-smoking normotensive volunteers, taking no medication. They were divided into three age-subgroups (n=25/group): 18–30, 50–59, and 60–70 years (women: 54, 27 and 23%, respectively). All subjects underwent clinical and laboratory evaluation. Peripheral endothelial function, expressed in cutaneous blood flow (delta CBF), was assessed through cutaneous microcirculation dilation by the non-invasive method using Laser Doppler Speckle Contrast Imaging (LSCI, Perimed) coupled with iontophoresis to locally deliver 125 nmoles of acetylcholine (Ach). The CFR was determined by cardiac magnetic resonance (CMR) coupling with an intravenous infusion of adenosine at 140 μg/kg/min for at least 3 minutes. Results Age was associated with a 23% reduction of peripheral endothelial function (delta CBF, p=0.005) in the elderly group (60–70y) vs. the younger one (18–30y) (median: 56.4 vs. 73.6). By contrast, calculated CFR was unchanged (median: 4.1 vs. 4.2, p=0.38). No relationship was observed between peripheral endothelial function (delta CBF) and CFR (r=0.01, p&amp;gt;0.97) in healthy volunteers. Conclusion In healthy volunteers, ageing is associated with a progressive peripheral but not with a coronary vascular dysfunction. This suggests that the impact of age on endothelial dysfunction depends on different vascular beds. Peripheral endothelial function assessment does not predict coronary vascular function in healthy volunteers. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Servier

SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.

BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe.MethodsSTZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV).FindingsSP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice.InterpretationOur work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN.FundingPlease see funding sources.

Impact of the menstrual cycle on peripheral vascular function in premenopausal women: systematic review and meta-analysis.

Fluctuations in endogenous hormones estrogen and progesterone during the menstrual cycle may offer vasoprotection for endothelial and smooth muscle (VSM) function. While numerous studies have been published, the results are conflicting, leaving our understanding of the impact of the menstrual cycle on vascular function unclear. The purpose of this systematic review and meta-analysis was to consolidate available research exploring the role of the menstrual cycle on peripheral vascular function. A systematic search of MEDLINE, Web of Science, and EMBASE was performed for articles evaluating peripheral endothelial and VSM function across the natural menstrual cycle: early follicular (EF) phase versus late follicular (LF), early luteal, mid luteal, or late luteal. A meta-analysis examined the effect of the menstrual cycle on the standardized mean difference (SMD) of the outcome measures. Analysis from 30 studies (n = 1,363 women) observed a "very low" certainty of evidence that endothelial function increased in the LF phase (SMD: 0.45, P = 0.0001), with differences observed in the macrovasculature but not in the microvasculature (SMD: 0.57, P = 0.0003, I2 = 84%; SMD: 0.21, P = 0.17, I2 = 34%, respectively). However, these results are partially explained by differences in flow-mediated dilation [e.g., discrete (SMD: 0.86, P = 0.001) vs. continuous peak diameter assessment (SMD: 0.25, P = 0.30)] and/or menstrual cycle phase methodologies. There was a "very low" certainty that endothelial function was largely unchanged in the luteal phases, and VSM was unchanged across the cycle. The menstrual cycle appears to have a small effect on macrovascular endothelial function but not on microvascular or VSM function; however, these results can be partially attributed to methodological differences.

Brain imaging factors associated with progression of subcortical hyperintensities in CADASIL over 2-year follow-up.

Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebral small vessel disease manifesting with stroke, migraine and dementia in adults. The disease displays significant phenotypic variability that is incompletely explained. Early abnormalities in vascular function have been shown in animal models. We postulated that studying changes in vascular function may offer insights into disease progression. Twenty-two subjects with CADASIL [50% female, 50 (±11) years] from 19 pedigrees were included in a longitudinal multimodality study using brain magnetic resonance imaging (MRI), clinical measures, neuropsychology and measures of peripheral vascular function. MRI studies included measurement of structural brain changes, cerebral blood flow (CBF) and cerebrovascular reactivity by arterial spin labelling and a CO2 respiratory challenge. Over 2years, new stroke or transient ischaemic attack (TIA) occurred in five (23%) subjects and new significant disability in one (5%). There were significant increases in number of lacunes, subcortical hyperintensity volume and microbleeds, and a decrease in brain volume. CBF declined by 3.2 (±4.5)ml/100g/min over 2years. CBF and carotid-femoral pulse wave velocity at baseline predicted change in subcortical hyperintensity volume at follow-up. Carotid intima-media thickness and age predicted brain atrophy. Baseline CBF was lower in subjects who showed a decline in attention and working memory. Cerebral blood flow predicts radiological progression of hyperintensities and thus is a potential biomarker of disease progression in CADASIL. Over 2years, there were changes in several relevant imaging biomarkers (CBF, brain volume, lacunes, microbleeds and hyperintensity volume). Future studies in CADASIL should consider assessment of CBF as prognostic factor.

A high salt meal does not impair cerebrovascular reactivity in healthy young adults.

A high sodium (Na+) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty‐seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross‐over study. Participants were given a low Na+ meal (LSM; 138 mg Na+) and a high Na+ meal (HSM; 1,495 mg Na+) separated by ≥ one week. Serum Na+, beat‐to‐beat BP, middle cerebral artery velocity (transcranial Doppler), and end‐tidal carbon dioxide (PETCO2) were measured pre‐ (baseline) and 60 min post‐prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow‐mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p < .01). Cerebrovascular reactivity to hypercapnia (meal effect: p = .41) and to hypocapnia (meal effect: p = .65) were not affected by the HSM. Contrary with previous findings, FMD was not reduced following the HSM (meal effect: p = .74). These data suggest that a single high Na+ meal does not acutely impair cerebrovascular reactivity, and suggests that despite prior findings, a single high Na+ meal does not impair peripheral vascular function in healthy adults.

Non-invasive ventilation improves exercise tolerance and peripheral vascular function after high-intensity exercise in COPD-HF patients

AimEvaluate the acute effects of non-invasive positive pressure ventilation (NiPPV) during high-intensity exercise on endothelial function in patients with coexisting chronic obstructive pulmonary disease (COPD) and heart failure (HF). MethodsThis is a randomized, double blinded, sham-controlled study involving 14 COPD-HF patients, who underwent a lung function test and Doppler echocardiography. On two different days, patients performed incremental cardiopulmonary exercise testing (CPET) and two constant-work rate tests (80% of CPET peak) receiving Sham or NiPPV (bilevel mode - Astral 150) in a random order until the limit of tolerance (Tlim). Endothelial function was evaluated by flow mediated vasodilation (FMD) at three time points: 1) Baseline; 2) immediately post-exercise with NiPPV; and 3) immediately post-exercise with Sham. ResultsOur patients had a mean age of 70 ± 7 years, FEV1 1.9 ± 0.7 L and LVEF 41 ± 9%. NIPPV resulted in an increased Tlim (NiPPV: 130 ± 29s vs Sham: 98 ± 29s p = 0.015) and SpO2 (NiPPV: 94.7 ± 3.5% vs Sham: 92.7 ± 5.2% p = 0.03). Also, NiPPV was able to produce a significant increase in FMD (%) (NiPPV: 9.2 ± 3.1 vs Sham: 3.6 ± 0.7, p < 0.05), FMD (mm) (NiPPV: 0.41 ± 0.18 vs Sham: 0.20 ± 0.11, p < 0.05), Blood flow velocity (NiPPV: 33 ± 18 vs Baseline: 20 ± 14, p < 0.05) and Shear Stress (SS) (NiPPV: 72 ± 38 vs Baseline: 43 ± 25, p < 0.05). We found correlation between Tlim vs. ΔSS (p = 0.03; r = 0.57). Univariate-regression analysis revealed that increased SS influenced 32% of Tlim during exercise with NiPPV. ConclusionNiPPV applied during high-intensity exercise can acutely modulate endothelial function and improve exercise tolerance in COPD-HF patients. In addition, the increase of SS positively influences exercise tolerance.

Sleep duration regularity, but not sleep duration, is associated with microvascular function in college students.

Vascular dysfunction is a hypothesized mechanism linking poor sleep habits to an increased incidence of cardiovascular diseases (CVDs). However, the vascular profile associated with free-living sleep duration and sleep regularity has not been well elucidated, particularly in young adults. Thus, this study aimed to evaluate the associations between mean sleep duration, regularity in sleep duration, and peripheral vascular function in young adult college students. Fifty-one healthy undergraduate students (20 ± 1 years) completed 14 days of 24-hour wrist actigraphy and subsequent vascular assessments. Macrovascular function was measured using brachial artery flow-mediated dilation (FMD) while microvascular function was measured via passive leg movement (PLM). Mean sleep duration was unrelated to FMD and PLM. Conversely, more irregular sleep duration (14-day sleep duration standard deviation [SD]) was unfavorably associated with all three measures of PLM-induced hyperemia (peak leg blood flow [LBF], p = 0.01; change in LBF from baseline to peak, p < 0.01; LBF area under the curve, p < 0.01), and remained significant in regression models which adjusted for sex, body mass index, blood pressure, physical activity, alcohol and caffeine consumption, and sleep duration (all p < 0.05). When using a median split to dichotomize "low" and "high" sleep duration SD groups, those demonstrating high variability in sleep duration exhibited ~45% lower PLM responses compared with those demonstrating low variability. Irregular sleep duration is associated with poorer microvascular function as early as young adulthood. These findings support the growing body of evidence that irregular sleep patterns may be an independent and modifiable risk factor for CVD.

Long-Term and Acute Benefits of Reduced Sitting on Vascular Flow and Function.

Sedentary behavior increases the risk for cardiovascular and cerebrovascular disease. To understand potential benefits and underlying mechanisms, we examined the acute and long-term effect of reduced sitting intervention on vascular and cerebrovascular function. This prospective study included 24 individuals with increased cardiovascular risk (65 ± 5 yr, 29.8 ± 3.9 kg·m-2). Before and after 16-wk reduced sitting, using a mobile health device with vibrotactile feedback, we examined (i) vascular function (flow-mediated dilation [FMD]), (ii) cerebral blood flow velocity (CBFv, transcranial Doppler), and (iii) cerebrovascular function (cerebral autoregulation [CA] and cerebral vasomotor reactivity [CVMR]). To better understand potential underlying mechanisms, before and after intervention, we evaluated the effects of 3 h sitting with and without light-intensity physical activity breaks (every 30 min). The first wave of participants showed no change in sedentary time (n = 9, 10.3 ± 0.5 to 10.2 ± 0.5 h·d-1, P = 0.87). Upon intervention optimization by participants' feedback, the subsequent participants (n = 15) decreased sedentary time (10.2 ± 0.4 to 9.2 ± 0.3 h·d-1, P < 0.01). This resulted in significant increases in FMD (3.1% ± 0.3% to 3.8% ± 0.4%, P = 0.02) and CBFv (48.4 ± 2.6 to 51.4. ±2.6 cm·s-1, P = 0.02), without altering CA or CVMR. Before and after the 16-wk intervention, 3-h exposure to uninterrupted sitting decreased FMD and CBFv, whereas physical activity breaks prevented a decrease (both P < 0.05). CA and CVMR did not change (P > 0.20). Long-term reduction in sedentary behavior improves peripheral vascular function and cerebral blood flow and acutely prevents impaired vascular function and decreased cerebral blood flow. These results highlight the potential benefits of reducing sedentary behavior to acutely and chronically improve cardio- or cerebrovascular risk.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Exercise training improves vascular function in patients with Alzheimer\u2019s disease

PurposeVascular dysfunction has been demonstrated in patients with Alzheimer’s disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD.MethodsThirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate–high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session.ResultsEX group has increased FMD% (+ 3.725%, p < 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p < 0.05; SR + 134%, p < 0.05), but not during CTRL treatment.ConclusionExercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population.

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Peripheral And Cerebral Vascular Function With Advancing Age: Evidence Of A Link

Peripheral vascular dysfunction has been documented to progress with advancing age, and age itself is the greatest risk factor for developing dementia. However, the likely link between peripheral and cerebral vascular function with aging has yet to be clearly investigated. PURPOSE: Therefore, the purpose of this study was to assess peripheral and cerebral vascular function in both young and old healthy adults and examine the relationship between the responsiveness of these vascular beds. METHODS: Peripheral vascular function was assessed with passive leg movement (PLM: blood flow ∆ peak and AUC), and cerebral vascular function was assessed by the breath hold acceleration index (BHAI) in 11 healthy adult males (7 old: 68±3 yr; 4 young: 23±3 yr). Doppler ultrasound was used to measure both common femoral artery blood flow and middle cerebral artery velocity. RESULTS: Peripheral vascular function was significantly attenuated in the old adults compared to the young (PLM AUC: 116±83 vs. 424±118 ml, p=0.001; PLM ∆ peak: 378±124 vs. 950±64 ml/min, p<0.001). Cerebral vascular function tended to be lower in the old compared to the young with a large effect size (BHAI: 1.36 ±67 vs. 2.4±1.4; d=0.95, p=0.132). However, even with a relatively limited sample size, there was a significant positive relationship between PLM AUC and BHAI (r=0.65, p=0.03). CONCLUSIONS: The identification of a relationship between the function of the peripheral and cerebral vascular beds (leg and brain) is an important step toward a better understanding of the global mechanisms of aging on the vasculature and likely age-related dementia.