Brachial Artery Flow Research Articles

Influence of oxygen enriched gases during decompression on bubble formation and endothelial function in self-contained underwater breathing apparatus diving: a randomized controlled study

AimTo assess the effect of air, gas mixture composed of 50% nitrogen and 50% oxygen (nitrox 50), or gas mixture composed of 1% nitrogen and 99% oxygen (nitrox 99) on bubble formation and vascular/endothelial function during decompression after self-contained underwater breathing apparatus diving.MethodsThis randomized controlled study, conducted in 2014, involved ten divers. Each diver performed three dives in a randomized protocol using three gases: air, nitrox 50, or nitrox 99 during ascent. The dives were performed on three different days limited to 45 m sea water (msw) depth with 20 min bottom time. Nitrogen bubbles formation was assessed by ultrasound detection after dive. Arterial/endothelial function was evaluated by brachial artery flow mediated dilatation (FMD) before and after dive.ResultsNitrox 99 significantly reduced bubble formation after cough compared with air and nitrox 50 (grade 1 vs 3 and vs 3, respectively, P = 0.026). Nitrox 50 significantly decreased post-dive FMD compared with pre-dive FMD (3.62 ± 5.57% vs 12.11 ± 6.82% P = 0.010), while nitrox 99 did not cause any significant change.ConclusionNitrox 99 reduced bubble formation, did not change post-dive FMD, and decreased total dive duration, indicating that it might better preserve endothelial function compared with air and nitrox 50 dive protocols.

Interwoven Nitinol Stents to Treat Radiocephalic Anastomotic Arteriovenous Fistula Stenosis

Purpose: To determine the clinical outcomes in hemodialysis patients after implantation of a Supera stent to treat juxta-anastomotic stenosis in radiocephalic arteriovenous fistulas (AVF). Materials and Methods: A single-center retrospective study was conducted of 42 consecutive patients (mean age 66.7 years, range 40–84; 26 men) who had a failing AVF due to juxta-anastomotic stenosis treated with the interwoven Supera stent between February 2014 and February 2018. A third of the patients had previous juxta-anastomotic intervention (either balloon angioplasty or open surgical revision). Results: The stent was inserted successfully in all patients. Overall mean follow-up was 12.2±8.2 months (range 3.8–38.3). Juxta-anastomotic segment primary patency estimates at 6 and 12 months were 92.5% and 59.8%, respectively, with assisted primary patency rates of 97.5% and 92.9%. Reintervention (elective drug-coated balloon angioplasty) occurred at a rate of 0.31 procedures/year. Two AVFs thrombosed during the 1-year follow-up and were revascularized using balloon angioplasty. Ultrasound measurements of brachial artery flow rates increased significantly from 543.5±96.72 mL/min (range 430–644) before intervention to 919.2±355.9 mL/min (range 200–1600) after intervention (p=0.047). Arterial pressures on hemodialysis improved from −142.3±24.9 mm Hg (range −100 to −180) to −123.4±21.9 mm Hg (range −100 to −184; p=0.051). No AVFs were lost or abandoned during the follow-up period. Conclusion: The interwoven Supera stent is a promising treatment for failing AVFs with juxta-anastomotic stenosis. Encouraging 1-year primary and assisted primary patency was demonstrated, with a low reintervention rate. This treatment facilitates long-term maintenance of AVF vascular accesses.

The role of enzyme and substrate dependence in NO‐mediated vascular dysfunction with aging

The typical aging process results in arterial dysfunction, often attributed to a fall in nitric oxide (NO) bioavailability. The diminished efficacy of the enzyme responsible for NO production, endothelial nitric oxide synthase (eNOS), and the required substrate, extracellular L‐arginine, may play a role in age‐related vascular dysfunction. Supplementation of tetrahydrobiopterin (BH4), a cofactor which recouples eNOS, and chronic supplementation of L‐Citrulline (L‐Cit), which increases plasma L‐arginine, may both increase NO bioavailability. Therefore, this study sought to evaluate the role of increased eNOS activity or L‐arginine concentration alone, and the combination of both, in the NO‐mediated vascular dysfunction associated with advancing age. Eight old subjects (73 ± 6 yr) received BH4 (100 mg per kg wt) acutely and underwent a 7 day supplementation of L‐Citrulline (6 g per day). Vascular function was assessed with: brachial artery flow mediated dilation (FMD: %) and passive leg movement (PLM: blood flow ΔPeak and AUC). Assessments were performed with and without BH4, both before and after L‐Citrulline supplementation (Ctrl; BH4; L‐Cit; L‐Cit + BH4). PLM ΔPeak increased ≈35% and ≈27% in the BH4 and L‐Cit + BH4 conditions, respectively (p< 0.05). PLM AUC increased ≈114% (p< 0.05) in the L‐Cit + BH4 condition. No significant intervention‐induced changes in FMD were detected. Thus, age‐induced vascular dysfunction, as measured by PLM which is likely more NO mediated than FMD, appears to belimited to a greater degree by eNOS function than eNOS substrate. However, the combination of improved eNOS coupling with increased eNOS substrate results in the greatest enhancement in vascular function in this population.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P137: Impaired Microvascular and Endothelial Function Among African-Americans With Coronary Artery Disease

Background: African-Americans have disproportionately higher burden of mortality from coronary artery disease (CAD) compared to Caucasians even after adjusting for socioeconomic and cardiovascular risk factors. Racial differences in arterial stiffness have been described, but data on microcirculatory and endothelial vascular function are more limited and it is unknown whether they differ by race in CAD patients. Methods: We studied 313 patients with a recent history of myocardial infarction (MI). Microvascular function was assessed by digital pulse amplitude tonometry (EndoPAT) to determine reactive hyperemia index (RHI), and endothelial function as brachial artery flow mediated dilation (FMD) using ultrasound. Arterial stiffness was assessed using applanation tonometry (Sphygmocor) to determine pulse-wave velocity (PWV) and central augmentation index (C-AIx). Data on sociodemographics, cardiovascular risk factors, medication use, and CAD severity were collected. Multivariate linear regression models were used to assess the relationship between race and various vascular function measures with adjustment for risk factors. Measures of arterial stiffness were included as control factors in the adjusted model for FMD and RHI. Results: The mean age of this post-MI sample was 51 years (± 6.7 SD); 50% were African-Americans and 49% were female. Compared to Caucasians, African-Americans had worse microvascular function as indicated by lower mean (± SD) RHI (1.7±0.5 vs 2.0±0.6, p<0.0001) and worse endothelial function [FMD mean (3.4±2.4 vs 4.7±3.1, p=0.0002)]. African-Americans also had greater arterial stiffness, including a higher mean C-AIx (26.5±9.0 vs 23.0±9.3, p=0.0019) and PWV (7.7±2.0 vs 7.1±1.8, p<0.0267). After adjustment for cardiovascular risk factors, medications, CAD severity, and arterial stiffness (C-AIx and PWV), black race remained significantly associated with lower RHI (β=-0.30, p<0.001) and FMD (β=-1.06, p=0.004). Conclusion: African-Americans with CAD have impaired microvascular and endothelial vasodilatory function compared to Caucasians, independent of CAD risk factors and arterial stiffness. Racial differences in microcirculatory and endothelial function may contribute to worse outcomes among African-Americans with CAD.

Using CorMatrix for partial and complete (re)construction of arteriovenous fistulas in haemodialysis patients: (Re)construction of arteriovenous fistulas with CorMatrix.

CorMatrix is an acellular extracellular matrix that acts as a biological scaffold and remodels into site-specific tissue. We used it for the (re)construction of arteriovenous fistulas. In this prospective pilot case study, we used CorMatrix in six patients. We included patients who required vascular access reconstruction due to thrombosis of unsalvageable arteriovenous fistulas, patients with high-flow arteriovenous fistulas and patients with microvasculature in which autologous arteriovenous fistulas did not mature, requiring reconstruction with a graft. We sutured the CorMatrix plate into a tubular shape and then constructed arterial and venous anastomoses. There were no periprocedural complications, CorMatrix-related infections, bleeding or limb swelling after the procedures. CorMatrix was first punctured after 8-10 weeks. In five patients, a percutaneous angioplasty due to CorMatrix stenosis was performed; in one patient, a stent was placed due to refractory stenosis. We observed eight thromboses during the observation period (four in one patient). Perianastomotic stenosis of CorMatrix and interdialytic hypotension were the causes of the thrombosis in five patients, cephalic arch stenosis in two patients and thromboembolism to the brachial artery and arteriovenous fistula in one patient. Thrombendarteriectomy was successful in 87.5% of patients, and one patient required arteriovenous fistula reconstruction. After a median observation period of 12.5 (range 4-23) months, all arteriovenous fistulas were patent, with a median brachial artery flow of 1450 (range 700-1700) mL/min. Arteriovenous fistula (re)construction with CorMatrix seems to be feasible and safe, with a relatively high incidence of neointimal hyperplasia, predominantly at venous anastomoses, but additional clinical studies are needed.

Abstract 60: Ischemic Conditioning Improves Brachial Artery Flow Mediated Dilation in Chronic Stroke Survivors

Introduction: Brachial artery flow mediated dilation (FMD) is a well-established measure of vascular endothelial health and is pathologically low in chronic stroke survivors. Ischemic conditioning (IC) is a cardioprotective stimulus and has been shown to improve FMD and enhance motor function in healthy humans. We recently showed that IC can improve paretic muscle strength and increase self-selected walking speed in stroke survivors. These improvements could be, in part, mediated by improved peripheral vascular function and increased blood flow to the exercising muscle. The effects of IC on vascular endothelial function post-stroke have not been investigated. Hypothesis: Two weeks of IC on the paretic leg of chronic stroke survivors will improve FMD in the non-paretic brachial artery. Methods: This was a prospective, randomized, blinded and controlled pilot study. Twenty chronic stroke survivors (>1-year post-stroke) received either IC (cuff inflation on the paretic leg for five minutes to 225 mmHg) or Sham IC (cuff inflation to 10 mmHg) every other day for two weeks (five on-off cycles per session). Brachial artery FMD was assessed using ultrasonography within 48 hours of the beginning and end of the intervention period. Results: Eight men and twelve women participated in this study. The mean age was 59 ± 16 years and the mean time post-stroke was 9 ± 9 years. Brachial artery FMD increased in the IC group from 6.2 ± 4.9% to 8.9 ± 3.9% (n=10; p=0.023, 2-way Repeated Measures ANOVA) while no change was observed in the Sham IC group (pre- vs. post = 3.8 ± 3.9% vs. 2.7 ± 3.1%, respectively; p=0.32, n=10). Expressed as the mean change in FMD, IC increased FMD by 2.8 ± 3.7% while no change was observed in the Sham IC group (delta FMD = -1.1 ± 3.4%; p=0.024 IC vs. IC Sham, unpaired t-test). Conclusions: Two weeks of IC increases brachial artery FMD in chronic stroke survivors. Taken together with our previous work that shows IC increases paretic muscle strength and walking speed in chronic stroke survivors, IC has the potential to improve both motor and cardiovascular function post-stroke. Future larger studies are needed to evaluate the efficacy of IC to improve stroke recovery and to identify the pathways involved which confer benefit to both the nervous and cardiovascular systems.

Continuous Simultaneous Recording of Brachial Artery Distension and Wall Shear Rate: A New Boost for Flow-Mediated Vasodilation.

Vascular ultrasound has been extensively applied in the clinical setting to noninvasively assess the endothelial function by means of the so-called brachial artery flow mediated dilation (FMD). Despite the usefulness in large-scale epidemiological studies, this approach has revealed some pitfalls for assessing vascular physiology and health in individual subjects. Mainly, a reliable FMD examination should be based on the simultaneous and reliable measurement of both the stimulus, i.e., the wall shear rate (WSR), and the response, i.e., the diameter change. However, multiple technical, practical, and methodological challenges must be faced to meet this goal. In this work, we present the technical developments needed to implement a system to enable the extensive and reliable clinical ultrasound FMD examination. It integrates both a hardware part, i.e., an upgraded version of the ultrasound advanced open platform (ULA-OP), and a software part, i.e., a signal processing and data analysis platform. The system was applied for a two-center pilot clinical study on 35 young and healthy volunteers. Therefore, we present here the results of a statistical analysis on magnitude, time-course, and kinetic parameters of WSR and diameter trends that allowed us to accurately explore the vasodilatory response to the dynamic WSR changes. Our observations demonstrate that a direct and accurate estimation of WSR stimulus by multigate spectral Doppler allows understanding brachial artery vasodilatory response to reactive hyperemia. Drawing inferences on WSR stimulus from the diameter response along with an inaccurate estimation of WSR may cause further uncertainties for the accurate interpretation of the FMD response.

Application of ultrasonography in monitoring the complications of autologous arteriovenous fistula in hemodialysis patients.

This study aims to evaluate the application of color Doppler ultrasound in monitoring the complications of autologous arteriovenous fistula in hemodialysis patients.Patients with maintenance hemodialysis who underwent autologous arteriovenous fistula were enrolled in this cross-sectional study. Ultrasound was used to detect fistula complications (stenosis and thrombosis), brachial artery diameter, and hemodynamic parameters. The ultrasound parameters were analyzed and screened to identify the most important indicator for monitoring complications.In all, 89 patients were included. Ultrasound showed 72 cases (80.90%) had normal fistula structure, and 17 cases (19.10%) had complications. The diameter, time-averaged mean velocity, flow volume, and diastolic peak velocity of brachial artery in complication group were significantly lower than those of noncomplication group (P < .05). The brachial artery pulsatility index and resistance index of complication group were significantly higher than those of noncomplication group (P < .05). There was no significant difference in peak flow velocity between complication and noncomplication group (P > .05). Indicators showed statistical significance were grouped based on quantiles. The incidence of complications was higher when the brachial artery diameter was ≤5.40 mm, or brachial artery flow was ≤460 mL/ min, or brachial artery pulsatility index was >1.04, or brachial artery resistance index was >0.60.Ultrasound monitoring of brachial artery diameter and hemodynamic parameters can help early detection of fistula complications. When the brachial artery diameter was ≤5.40 mm, or brachial artery flow was ≤460 mL/min, or brachial artery pulsatility index was >1.04, or brachial artery resistance index >0.60, stenosis or thrombosis should be checked to prevent fistula failure.

DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition.

DPP (dipeptidyl peptidase)-4 inhibitors are antidiabetic drugs that may increase heart failure in high-risk patients. NPY (neuropeptide Y) is coreleased with norepinephrine, causes vasoconstriction via the Y1 receptor, and is degraded by DPP4 to NPY (3-36) in vitro. NPY (3-36) decreases release of norepinephrine via the Y2 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the vasoconstrictor effect of NPY. Eighteen nonsmokers (12 healthy controls and 6 with type 2 diabetes mellitus) participated in 1 of 2 randomized, double-blind, placebo-controlled crossover studies. First, subjects were randomized to order of treatment with sitagliptin 100 mg/d versus placebo for 7 days separated by 4-week washout. On the last day of treatment, NPY was infused by brachial artery and forearm blood flow was measured using plethysmography. Blood samples were collected after each dose. NPY infusions were repeated after 90-minute washout and intra-arterial enalaprilat. Second, 5 healthy subjects were randomized to crossover treatment with sitagliptin 100 mg/d plus valsartan 160 mg/d versus placebo plus valsartan. NPY infusions were performed on the seventh day of treatment. NPY caused dose-dependent vasoconstriction. During enalaprilat, sitagliptin significantly potentiated NPY-induced vasoconstriction in controls and diabetics ( P≤0.02 for forearm blood flow in either group). Baseline norepinephrine release was increased during sitagliptin and enalaprilat, but not further by NPY. Sitagliptin increased the ratio of NPY to NPY (3-36). During valsartan, sitagliptin also significantly potentiated NPY-induced vasoconstriction ( P=0.009 for forearm blood flow). Potentiation of endogenous NPY could contribute to cardiovascular effects of DPP4 inhibitors in patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

Correlation analysis of age with endothelial function and oxidative stress in the healthy population

Objective To evaluate the vascular endothelial function and oxidative stress level in the healthy population, and to provide evidence for preliminary nursing care regarding abnormal endothelial function in healthy people. Methods A total of 296 healthy people who had physical examination in Beijing Hospital from March to October 2016 were selected in this study using convenience sampling. The participants were divided into the youth group (30-44 years old) , middle-aged group (45-59 years old) and elderly group (60-79 years old) . The routine biochemical indexes, blood nitric oxide (NO) , blood endothelin (ET-1) , blood malondialdehyde (MDA) , blood superoxide dismutase (SOD) , and brachial artery flow mediated endothelium dependent vasodilatation function (FMEDD) were measured for the participants. Results There were significant differences in FMEDD, NO and SOD among different age groups (P<0.05) . The age was negatively correlated with fasting FMEDD, NO and SOD (r=-0.767 8, -0.465 2, -0.625 0; P<0.05) . However, a positive correlation was found between age and ET-1 and MDA (r= 0.112 6, 0.095 7; P<0.05) . Conclusions The vascular endothelial function and antioxidant stress index decrease with age in the healthy population. The decline of vascular endothelial function in the elderly over 60 years old should be concerned. The elderly people should strictly control their blood pressure, blood glucose, blood lipid and other risk factors for vascular endothelial function to prevent endothelial dysfunction in the early stage, especially in people who have no history of hypertension, diabetes, or hyperlipidemia. Key words: Age groups; Vascular endothelial function; Oxidative stress

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease.

BackgroundEndothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.Methods and ResultsWe analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow–mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post–kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow–mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.ConclusionThe alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD‐associated vascular disease.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.

Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people.

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.

Endocan Levels and Endothelial Dysfunction in Patients With Sarcoidosis.

A systemic inflammatory reaction is a common feature of both sarcoidosis and atherosclerosis. Endothelial-cell specific molecule 1 (endocan) is a marker of vascular pathology which also shows a correlation with inflammation, endothelial dysfunction, and atherosclerosis. The objective of this study was to evaluate the vascular involvement in sarcoidosis using serum endocan levels and brachial artery flow-mediated dilation (FMD), a marker of endothelial dysfunction. We included 53 patients with sarcoidosis without conventional cardiovascular risk factors and 40 healthy controls. Endothelial function was assessed using FMD. Endocan concentrations were measured using a commercially available enzyme-linked immunoassay. Patients with sarcoidosis had significantly higher endocan levels (306 [68] ng/mL vs 269 [73] ng/mL; P = .039) and lower FMD (2.7% [2.3%-3.2%] vs 8% [5%-13%]; P < .001) compared with the healthy group. A negative correlation was found between endocan levels and FMD in the sarcoidosis group ( r = -.325, P < .007). We conclude that sarcoidosis is associated with high levels of endocan and lower FMD values, which may indicate endothelial dysfunction and an early stage of atherosclerosis.

Endothelial Function Correlates With Aerobic Fitness In Adults With Fasting Hyperglycemia Plus Impaired Glucose Tolerance

BACKGROUND: Impaired glucose tolerance (IGT) elevates type 2 diabetes and cardiovascular disease (CVD) risk above and beyond impaired fasting glucose (IFG) alone. Endothelial dysfunction and arterial stiffness have been implicated in chronic disease and linked to reduced aerobic fitness. However, it is unknown if the presence of IGT attenuates vascular function in people with IFG. We tested the hypothesis that adults with IFG+IGT have endothelial dysfunction and arterial stiffness in relation to low aerobic fitness when compared with IFG counterparts. METHODS: Middle-aged, obese adults with IFG (n=11, 58.3±10yrs; 34.0±7.4 kg/m2; (FBG: 105.6±6.1mg/dl, 2-hr glc: 120.7±28.1mg/dl) and IFG+IGT (n=14, 61±8.1yrs; 33.1±3.3 kg/m2; FBG: 104.2±10.5mg/dl, 2 hour glc: 165.4±2mg/dl) were compared in this cross-sectional study following a 75g OGTT screening based on ADA criteria. Aerobic fitness (VO2peak) was assessed with a cycle ergometer via indirect calorimetry, and body fat was determined by BIA (InBody®). After an overnight fast, brachial artery flow mediated dilation (FMD) was used to assess endothelial function by ultrasound and arterial stiffness was determined via augmentation index (AI) and pulse wave velocity (PWV) via applanation tomography. A 180-min OGTT was also performed to assess glucose tolerance. RESULTS: Although there was no significant difference between IFG and IFG+IGT for body fat (P=0.94), VO2peak (P=0.46), FMD (P=0.42), AI (P=0.71), or PWV (P=0.95), elevated VO2peak was strongly correlated with a higher FMD in people with IFG+IGT (r=0.57, P=0.04), but not IFG (r=0.1, P=0.99). Moreover, elevated postprandial blood glucose at 180 min was associated with lower VO2peak (r=-0.51, P=0.06) and FMD (r=-0.54, P=0.05) in IFG+IGT, but not IFG (r=-0.19, P=0.57; r=-0.22, P=0.52, respectively). CONCLUSION: Endothelial function was significantly related to aerobic fitness in adults with IFG+IGT but not IFG. These data highlight that post-prandial hyperglycemia may modify vascular function and training adaptation uniquely between prediabetes phenotypes. Additional research is needed to determine the effect of training across exercise doses on skeletal muscle vascular glucose regulation to optimize diabetes and/or CVD prevention.

Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.

Cardiovascular outcomes of Nephrotic syndrome in childhood (CVONS) study: a protocol for prospective cohort study

BackgroundNephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. Atherosclerosis in childhood is mostly subclinical and endothelial dysfunction is known to precede this. Evidence for screening for endothelial dysfunction and cardiovascular risk factors and early identification of premature onset of atherosclerosis in childhood NS remains tenuous in the absence of well-designed prospective studies addressing cardiovascular comorbidity in NS. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls.MethodsIn a multi-centric prospective cohort study, 70 Steroid Resistant NS (SRNS), 70 Steroid Sensitive (SSNS) patients along with 70 Healthy Controls are being recruited. After a baseline assessment of functional and structural status of heart (2D Echocardiography), arteries (Carotid Doppler and Intima Media Thickness measurements) and microcirculation [a combination of 2D Echocardiography, Laser Doppler Flowmetry (LDF) and Brachial Artery Flow mediated dilation (FMD) and Nail Fold Capillaroscopy (NFC)], the patients are being investigated for endothelial dysfunction. Venous blood sample (15 ml) is being collected for routine investigations and assay of biochemical endothelial markers through Flow Cytometry. The patients will be followed up at 12 months and 24 months after the recruitment to look for any change from baseline period.DiscussionThis study will able to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS. Findings on characterization of prevalence of endothelial dysfunction and subclinical markers may be used to design future randomized controlled trials for evaluating the efficacy of preventive and therapeutic interventions in reducing the incidence of cardiovascular disease.

Vascular Function after Sauna Bathing in Healthy Older Adults

Repeated heat exposure by immersion in warm water improves vascular function in healthy young adults. This observation could explain the health benefits of sauna bathing reported in population‐based studies, in which regular sauna sessions lasting more than 19 minutes were shown to significantly decrease the risk of cardiovascular mortality. However, it is unknown if such sauna durations improve vascular function in older adults. The purpose of this study was to determine if 20 min of sauna bathing acutely improves vascular function in healthy older adults.Six older adults (4 women) without cardiovascular disease and risk factors (age range: 57–71 yrs) underwent a sauna bathing session consisting of 2 bouts of 10 min in a dry Finnish sauna (80°C) separated by 10 min of seated rest outside the sauna. Prior to and following sauna bathing, flow‐mediated dilation (FMD) of the brachial artery in response to reactive hyperemia induced by 5 min of forearm ischemia was assessed by Doppler ultrasound after a minimum of 30 min rest in the supine position in a quiet and thermoneutral environment. The percent change in artery diameter from baseline to peak was used as an index of macrovascular function, whereas post‐occlusive reactive hyperemia (PORH), estimated by the brachial artery flow area‐under‐the‐curve above baseline during the 3 min following ischemia, was used to evaluate microvascular function. Heart rate (HR), mean arterial pressure (MAP), oral temperature (Toral) and mean skin temperature (Tsk) were monitored throughout the study.Sauna caused an increase in HR (55 ± 8 to 86 ± 10 bpm, P&lt;0.01), mean Tsk (33.0 ± 0.5 to 40.7 ± 0.7°C, P&lt;0.01) and Toral (36.7 ± 0.3 to 37.4 ± 0.2°C, P=0.025) while changes in MAP were not statistically different (100 ± 8 to 90 ± 4 mmHg, p=0.137). At the time of FMD assessment, HR (53 ± 5 and 52 ± 5 bpm, P=0.56), MAP (92 ± 6 and 90 ± 5 mmHg, P=0.59) and Toral (36.8 ± 0.3 and 36.9 ± 0.1 °C, P=0.27) were similar before and after sauna bathing, whereas mean Tsk was elevated prior to the post‐sauna FMD assessment (34.3 ± 0.4 vs. 32.9 ± 0.5°C, P&lt;0.01). FMD was similar before and after sauna bathing (4.79 ± 2.21% vs. 4.86 ± 2.73%, P=0.93). PORH was also similar before and after sauna bathing (286 ± 198 vs. 380 ± 168 ml, P=0.18).These preliminary results indicate that macro‐ and microvascular functions are unaffected by two 10 min bouts of sauna bathing at 80°C in healthy older adults.Support or Funding InformationFunded by Fondation de l'Institut de cardiologie de Montréal and by Fonds de Recherche du Québec – Santé.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Blood Pressure and Vascular Function in Hypertensive Individuals: Partitioning cause and effect

IntroductionVascular dysfunction is a hallmark of hypertension and contributes to an increased risk of cardiovascular disease. Pharmacological interventions to treat hypertension generally result in improved blood pressure status and concomitant improvements in vascular function. However, recent findings have challenged this notion as vascular dysfunction appears to persist despite blood pressure control with antihypertensive medications. Importantly, medications differ in their vasoactive properties and may have direct effects on the vasculature independent of their impact on blood pressure. Therefore, it is difficult to discern if the potential improvements in vascular function are associated with lower blood pressure or a direct effect on vascular function. Utilizing the dietary approach of salt restriction this study examined the impact of reducing blood pressure on vascular function and peripheral hemodynamics in individuals with essential hypertension.MethodsHypertensive adults (male n=14, female n=8, 50±10 yr) completed two dietary phases: liberal sodium (LS) (200 mmol/d) followed by restricted sodium (RS) (10 mmol/day) diet for five days, respectively. Antihypertensive medications were withdrawn 2 weeks before the first intervention. Following each dietary phase, measurements of systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), arterial diameter and blood velocity (Doppler ultrasound) were assessed at rest, during brachial artery (BA) flow mediated dilation (FMD), and during progressive handgrip (HG) exercise performed at 15, 30 and 45% of maximal voluntary contraction (MVC).ResultsRS significantly lowered SBP (LS: 140±3, RS: 123±3 mmHg), DBP (LS: 85±2, RS: 79±2 mmHg) and MAP (LS: 103±2, RS: 94±2 mmHg) (all p&lt;0.05). Despite improvements in blood pressure, conduit artery function, as measured by FMD, was similar between conditions (LS: 4.6±0.4%; RS: 5.1±0.5%). Similarly, the hyperemic response during FMD, an assessment of microvascular function, was not different between conditions (LS: 548±43; RS: 615±44 ml). During HG exercise, MAP was lower at all exercise intensities during RS compared to LS (15% MVC; LS: 109±2 vs. RS: 102±2 mmHg; 30% MVC; LS: 113±2 vs. RS: 105±2 mmHg; 45% MVC; LS: 122±3 vs. RS: 112±3 mmHg) while vascular conductance and BA vasodilation were not different between LS and RS (p&gt;0.05).ConclusionDespite improvements in blood pressure at rest and during exercise, both conduit artery and microvascular function measured during FMD and HG exercise‐induced vasodilation were not improved. These findings support recent evidence that vascular dysfunction persists in individuals with hypertension independent of blood pressure status.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Diameter of inflow as a predictor of radiocephalic fistula flow.

The optimal method for vascular access surveillance is largely unknown. A previous case-control study suggested a simplified anatomical measure obtained by Doppler ultrasound-the narrowest segment of the circuit or "minimal luminal diameter" may identify patients with a dysfunctional radiocephalic arteriovenous fistula. The relationship between minimal luminal diameter and access flow (Qa) in the radiocephalic arteriovenous fistula has not previously been studied. Patients undergoing Doppler ultrasound of a radiocephalic arteriovenous fistula over an 8-month period were identified retrospectively. Minimal luminal diameter was identified and demographic and clinical data were collected. Qa was estimated by Doppler estimation of brachial artery flow. The relationship between minimal luminal diameter and Qa was examined by correlation and using different levels of minimal luminal diameter as a simplified measure to detect or exclude low Qa (<600 mL/min). A total of 81 Doppler ultrasound scans were performed. In all, 26 scans demonstrated brachial artery flow <600 mL/min. Simple logistic regression indicated a weak statistical relationship between the minimal luminal diameter and Qa (R2 = 0.27, p < 0.01). Minimal luminal diameter performed poorly as a marker of low Qa with low specificity, however, showed high negative predictive value for ruling out low Qa at a minimal luminal diameter of 3.2 mm or higher (94%). Qa estimated by brachial artery flow correlated well with Qa estimated by indicator dilution (R2 = 0.83, p < 0.01) without significant mean difference or proportional bias. Minimal luminal diameter correlates weakly with Qa. Low minimal luminal diameter values should not be used in isolation to determine low Qa for a radiocephalic arteriovenous fistula. Conversely, minimal luminal diameter >3.2 mm largely excludes a low-flow radiocephalic arteriovenous fistula in this cohort. Brachial artery flow is a reasonable measure of Qa in comparison with indicator dilution.

Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes

BackgroundPeople with type 2 diabetes (T2D) have impaired exercise capacity, even in the absence of complications, which is predictive of their increased cardiovascular mortality. Cardiovascular dysfunction is one potential cause of this exercise defect. Acute infusion of vitamin C has been separately shown to improve diastolic and endothelial function in prior studies. We hypothesized that acute vitamin C infusion would improve exercise capacity and that these improvements would be associated with improved cardiovascular function.MethodsAdults with T2D (n = 31, 7 female, 24 male, body mass index (BMI): 31.5 ± 0.8 kg/m2) and BMI-similar healthy adults (n = 21, 11 female, 10 male, BMI: 30.4 ± 0.7 kg/m2) completed two randomly ordered visits: IV infusion of vitamin C (7.5 g) and a volume-matched saline infusion. During each visit peak oxygen uptake (VO2peak), brachial artery flow mediated dilation (FMD), reactive hyperemia (RH; plethysmography), and cardiac echocardiography were measured. General linear mixed models were utilized to assess the differences in all study variables.ResultsAcute vitamin C infusion improved diastolic function, assessed by lateral and septal E:E’ (P < 0.01), but did not change RH (P = 0.92), or VO2peak (P = 0.33) in any participants.ConclusionAcute vitamin C infusion improved diastolic function but did not change FMD, forearm reactive hyperemia, or peak exercise capacity. Future studies should further clarify the role of endothelial function as well as other possible physiological causes of exercise impairment in order to provide potential therapeutic targets.Trial registration NCT00786019. Prospectively registered May 2008