Brachial Artery Blood Flow Research Articles

Flow-mediated dilation analysis coupled with nitric oxide transport to enhance the assessment of endothelial function.

Flow-mediated dilation (FMD), mainly mediated by nitric oxide (NO), aims to assess the shear-induced endothelial function, which is widely quantified by the relative change in arterial diameter after dilation (FMD%). However, FMD% is affected by individual differences in blood pressure, blood flow, and arterial diameter. To reduce these differences and enhance the assessment of FMD to endothelial function, we continuously measured not only the brachial artery diameter and blood flow with ultrasound but also blood pressure with noninvasive monitor during standard FMD test. We further constructed an analytical model of FMD coupled with NO transport, blood flow, and arterial deformation. Combining the time-averaged and peak values of arterial diameter, blood flow, and pressure, and the modeling, we assumed the artery was completely healthy and calculated an ideally expected FMD% (eFMD%). Then, we expressed the fractional flow-mediated dilation (FFMD%) for the ratio of measured FMD% (mFMD%) to eFMD%. Furthermore, using the continuous waveforms of arterial diameter, blood flow, and pressure, the endothelial characteristic parameter (ϵ) was calculated, which describes the function of the endothelium to produce NO and ranges from 1 to 0 representing the endothelial function from healthiness to complete loss. We found that the mFMD% and eFMD% between the young age (n = 5, 21.2 ± 1.8 yr) and middle age group (n = 5, 34.0 ± 2.1 yr) have no significant difference (P = 0.222, P = 0.385). In contrast, the FFMD% (P = 0.008) and ϵ (P = 0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (ϵ) may have the potential for specifically diagnosing the endothelial function.NEW & NOTEWORTHY FMD% is affected by various factors, which limits its ability to assess the endothelial function. We developed an analytical model of FMD process coupled with nitric oxide based on the mathematical modeling and physiological measurements. Two model-derived indicators (FFMD% and ϵ) were introduced based on the modeling. Our results indicated that FFMD% and ϵ may have the potential to distinguish the endothelial function between the young- and middle age groups.

Comparison of various zero‐dimensional models to analyze the brachial artery blood flow of an arterio‐venous fistula during hemodialysis procedure

AbstractOne of the most recommended vascular accesses for hemodialysis is an autogenous arterio‐venous fistula (AVF), which is a surgically created conduit between an artery and a vein. AVFs can be compromised by stenosis‐induced arterial or venous thrombosis. An effective and efficient mathematical fluid mechanical model can provide insight into the mechanisms for stenosis and thrombosis. In an earlier paper, a laminar entry flow model (Shah) was applied to a fifth order lumped parameter zero dimensional (0D) model to predict the inlet flow rate in the brachial artery of an AVF. ODE45, a built in MATLAB ordinary differential equation (ODE) solver, was used to produce the solution. The Shah model showed closer correlation with a computational fluid dynamics model, performed in COMSOL, than did the Poiseuille flow model. In this study, an outlet flow rate in the brachial artery of an AVF is generated with third, fourth, and fifth order lumped parameter zero dimensional models with laminar and turbulent flow conditions within different arterial segments. Butcher's sixth order Runge‐Kutta (RK) method was used as an ODE solver and the results were compared with the MATLAB ODE solvers (ODE45 and ODE113). The lumped parameter model solved with Butcher's sixth order RK method generated less oscillation with a more stable and consistent outlet flow rate in comparison to the other solvers. Brachial artery blood flow, modeled with Shah's entry flow equation in the inlet segment and Blasius turbulent equation modeled at the outlet segment prior to the beginning of the anastomosis, generated an average outlet flow rate similar to that of clinical data. The dependence of brachial artery on the flow equations indicates the importance of wisely selecting flow resistance models and the effect of blood pressure and peripheral resistance on fistula maturation. The average and peak flow rate also depended on the ODE solver. Third and fourth order lumped parameter models generated results similar to the fifth order model only at normal peripheral resistance. Therefore, this study can help to understand the AVF performance in vitro and guide the application of an appropriate lumped parameter model for blood flow prediction.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial.

Introduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension.Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models.Clinical Trial Registration: www.Clinicaltrials.gov, identifier: NCT03722199.

Skeletal muscle anabolic and insulin sensitivity responses to a mixed meal in adult patients with active Crohn's disease.

We have previously shown reduced protein balance in response to nutrition in paediatric Crohn's disease (CD) in remission, associated with reduced lean mass (sarcopenia) and reduced protein intake in males. We aim to compare skeletal muscle metabolic response to feeding in adult active CD and healthy volunteers. Eight CD participants with active disease (41.3±4.5yrs; BMI 26.9±1.5kg/m2) and eight matched healthy volunteers (Con) (41.2±4.3yrs; BMI 25.1±1.1kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialized hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20mins for 2hrs after the ingestion of a standardized mixed liquid meal. Net balance of branched chain amino acids (BCAA), glucose and free fatty acids across the forearm were derived. No differences in muscle BCAA, glucose or FFA net balance were found between CD and Con. Neither were differences in muscle mass and function, physical activity or diet found. CD did not differ from Con in whole body insulin and lipid responses, or in energy expenditure and fuel oxidation. Skeletal muscle mass, function, dietary protein intake and response to a test meal in an adult CD cohort with active disease is similar to that seen in healthy volunteers. Combining these results with our previous findings in paediatric patients suggests that age of onset and/or disease burden over time, as well as daily protein intake, may be significant in the development of sarcopenia in CD. Longitudinal studies investigating these factors are required.

Determinants of estimated failure load in the distal radius after stroke: An HR-pQCT study

Bone health is often compromised after stroke and the distal radius is a common site of fragility fractures. The macro- and mircoproperties of bone tissue after stroke and their clinical correlates are understudied. The objectives of the study were to use High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) to investigate the bone properties at the distal radius, and to identify the correlates of estimated failure load for the distal radius in people with chronic stroke. This was a cross-sectional study of 64 people with stroke (age: 60.8±7.7years, stroke duration: 5.7±3.9years) and 64 age- and sex-matched controls. Bilateral bone structural, densitometric, geometric and strength parameters of the distal radius were measured using HR-pQCT. The architecture, stiffness and echo intensity of the bilateral biceps brachii muscle and brachial artery blood flow were evaluated using diagnostic ultrasound. Other outcomes included the Fugl-Meyer Motor Assessment (FMA), Motor Activity Log (MAL), and Composite Spasticity Scale (CSS). The results revealed a significant side (paretic vs non-paretic for the stroke group, non-dominant vs dominant for controls) by group (stroke vs control) interaction effect for estimated failure load, cortical area, cortical thickness, trabecular number and trabecular separation, and all volumetric density parameters. Post-hoc analysis showed percent side-to-side differences in bone outcomes were greater in the stroke group than the control group, with the exception of trabecular thickness and intracortical porosity. Among the HR-pQCT variables, percent side-to-side difference in trabecular volumetric bone mineral density contributed the most to the percent side-to-side difference in estimated failure load in the stroke group (R2 change=0.334, β=1.106). Stroke-related impairments (FMA, MAL, CSS) were found to be significant determinants of the percent side-to-side difference in estimated failure load (R2 change=0.233, β=-0.480). This was the first study to examine bone microstructure post-stroke. We found that the paretic distal radius had compromised bone structural properties and lower estimated failure load compared to the non-paretic side. Motor impairment was a determinant of estimated bone strength at the distal radius and may be a potential intervention target for improving bone health post-stroke.

Relationship between vascular cell adhesion molecule-1 (VCAM-1), soluble receptor for advanced glycation end products (sRAGE) and functional hemodynamic parameters of arteriovenous fistula

The preferred vascular access for hemodialysis is represented by arteriovenous fistula (AVF) due to fewer complications and more prolonged survival. Considerable efforts have been made to identify biomarkers associated with AVF dysfunction, but results are conflicting. Vascular cell adhesion molecule (VCAM-1) and advanced glycation end products are involved in atherogenesis, vascular calcification, peripheral artery disease, and neointimal hyperplasia in renal and non-renal patients. The objective of this study was to evaluate whether there is an association between VCAM-1, soluble receptor for advanced glycation end products (sRAGE), NcarboxymethylLysine (CML), and arteriovenous fistula dysfunction (AVF). VCAM-1, sRAGE, and CML were performed using the ELISA technique in 88 HD patients. Ultrasound assessment of AVF reports brachial artery blood flow (Qa), brachial resistivity index (RI), presence of calcification, and the diameter. AVF dysfunction was defined as a brachial artery Qa ⩽ 500 ml/min or RI ⩾ 0.5. The median level of VCAM-1 [2676.5(2206.8-4203.9) versus 2613.2(1885.7-3161.8), p 0.026] was significantly higher in patients with AVF dysfunction compared to the rest of the patients. sRAGE and CML were higher in this group but without statistical significance. In patients with AVF dysfunction, significant positive correlations were found between VCAM-1and sRAGE (r = 0.417, p = 0.001), RI (r = 0.313, p = 0.046), dialysis vintage (r = 0.540, p < 0.001), AVF vintage (r = 0.336, p = 0.032), intima-media thickness (r = 0.423, p = 0.006) and C-reactive protein (r = 0.315, p = 0.045). VCAM-1 correlated inversely with cholesterol (r = -0.312, p = 0.047), triglycerides (r = -0.358, p = 0.021), body mass index (r = -0.388, p = 0.012). In multivariate regression analysis, VCAM-1 (p = 0.013) and sRAGE (p = 0.01) remained significant predictors of RI and Qa. Logistic regression disclosed calcification, VCAM-1, as risks factors for AVF dysfunction. The results we obtained showed that patients with AVF dysfunction had a significantly higher level of VCAM-l. A positive correlation between VCAM-1 and sRAGE was identified in this group.

Special Issue Guest Editorial: Basic and Applied Physiology Research

In this issue, the Journal brings readers a special issue in Basic Science and Applied Physiology Research with 4 original research reports. This is the beginning of a new section in our journal dedicated to physical therapists performing research in Basic Sciences and Applied Physiology. Producing high-level basic and applied physiological research is an important way to move the physical therapy profession forward.1 Although there are several physical therapists producing high-level research in this area, they often publish findings in Basic Science or Applied Physiology journals that are normally beyond clinical areas. With this special issue and the new section in the journal, the journal is closing the gap of knowledge by bringing high-level basic and applied physiological research to clinicians so that together we can advance the profession to improve the health of society. In this issue, Wooten et al consider carbon dioxide expiration and respiratory buffering as 2 potential important factors for performance fatigability. As hypothesized, both carbon dioxide expiration and respiratory buffering, measured by a cardiopulmonary exercise test, are good predictors of the changes that aerobic exercise training produces in performance fatigability.2,3 In addition, Rogers-Bosh et al bring an interesting feasibility study to introduce High-Intensity Interval Training (HIIT) in stroke survivors. In this study, the authors used treadmill HIIT, twice weekly in 17 adults with chronic stroke. They found that participants had a great attendance and that an exercise training program of such characteristics is feasible.3 Finally, Gurovich et al5 provide a novel methodology to measure carotid and brachial artery blood flow during exercise in vivo using vascular ultrasound. The methods they describe are important because most studies investigating exercise-induced endothelial sheer stress (ESS) are conducted in vitro or using in vivo models that do not account for the normal pulsatile nature of blood flow. Their findings help add to our understanding of exercise-induced ESS that forms the basis for some of the physiological benefits of exercise on vascular and endothelial function. In addition, this issue features the launch of the official CPTJ video methods library. This online resource will provide brief video descriptions of techniques included in the methods section of accepted publications. This was created to help remove the “black box” of intervention studies and improve translation to clinical practice. More specific to the current issue and section, this library also provides readers with a clearer understanding of research methods that may be novel to them. It may also help readers gain an understanding of how data were produced and collected for a given study. Our hope is that this exposure may encourage readers to consider using techniques and methods featured in these videos for future scientific inquiries. The first 3 videos are on Pulse Wave Analysis, Flow-Mediated Dilation, and Cardiopulmonary Exercise Tests, which are featured in the publications for this issue. Future video resources will be submitted as supplements by authors of accepted publication following the review process described on the forthcoming CPTJ Video Methods Library webpage. The journal is very excited about this new special issue and section, especially because the reception from multiple institutions was very well received. There are several more original research reports in the pipeline to continue offering high-level Basic Sciences and Applied Physiology research to our readers.

Influence of prostaglandins and endothelial-derived hyperpolarizing factors on brachial and popliteal endothelial-dependent function in young adults.

Heterogeneous flow-mediated dilation (FMD) and low-flow-mediated constriction (L-FMC) responses have been reported between upper- and lower-limb arteries. Radial artery L-FMC, but not FMD, responses are blunted when endothelial-derived hyperpolarizing factors (EDHFs) or prostaglandin production is inhibited in young adults. However, it is unknown if these mechanisms similarly impact endothelial-dependent responses in the brachial (BA) and popliteal (POP) arteries. We tested whether BA- and POP-L-FMC and FMD would be influenced by independent EDHF and prostaglandin inhibition. Eighteen participants (23 ± 3 yr; 6♀) completed three randomized and double-blinded ultrasound assessments following ingestion of an opaque capsule containing maltodextrin (control), 150 mg of fluconazole (EDHF inhibition), or 500 mg of aspirin (prostaglandin inhibition). POP resting diameter was reduced following fluconazole administration (6.13 ± 0.63 mm vs. 6.19 ± 0.65 mm in control, P = 0.03). Compared with control, fluconazole also blunted the relative L-FMC responses in both the BA (-2.1 ± 0.8% vs. -0.8 ± 1.0%, P = 0.001) and POP (-1.7 ± 1.1% vs. -0.8 ± 0.9%, P = 0.009). In contrast, aspirin did not impact either the BA (-1.9 ± 0.7%) or POP-L-FMC (-1.3 ± 0.6%) responses (both, P > 0.35). The FMD response was unchanged following fluconazole or aspirin administration in either artery (both, P > 0.36). Our findings demonstrate that EDHF mediates L-FMC responses in both the brachial and popliteal arteries. Complementary to the nitric oxide-mediated FMD response, L-FMC appears to provide information regarding the EDHF pathway. Future research should uncover if these mechanisms impact older adults and/or patient populations characterized by vascular endothelial dysfunction associated with low aerobic fitness and habitual physical activity levels.NEW & NOTEWORTHY We compared changes in upper- and lower-limb artery endothelial-dependent vasodilatory and vasoconstrictor responses between control, prostaglandin inhibition, and endothelial-derived hyperpolarizing factor inhibition conditions. Neither prostaglandins nor endothelial-derived hyperpolarizing factor influenced flow-mediated dilation responses in either the brachial or popliteal artery. In contrast, endothelial-derived hyperpolarizing factor, but not prostaglandins, reduced resting brachial artery blood flow and shear rate and resting popliteal artery diameter, as well as low-flow-mediated constriction responses in both the popliteal and brachial arteries.

The impact of preconditioning exercise on the vascular response to an oral glucose challenge.

Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of 3 different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; aged 23 ± 3 years) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30min; 65% peak oxygen consumption), high-intensity interval cycling exercise (10 × 1 min at 90% peak heart rate), and lower-load higher-repetition resistance exercise (25-35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p< 0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p< 0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. Novelty: We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an OGTT. Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.

Antecubital Vein Cannula Position Impacts Assessment of Forearm Glucose Uptake During an Oral Glucose Challenge in Healthy Volunteers.

Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein ('perforating' visit) and, at the bifurcation of superficial and perforating veins ('bifurcation' visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). Following glucose ingestion, forearm glucose uptake area under the curve was greater for the 'perforating' than for the 'bifurcation' visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.

Rolling massage acutely improves skeletal muscle oxygenation and parameters associated with microvascular reactivity: The first evidence-based study

Although it has been claimed that rolling massage (RM), may lead to improvements in skeletal muscle oxygenation, metabolism, blood flow, and vascular function, scientific evidence has not yet been provided. Thus, the current study investigated the effects of 30 s and 2 min of RM on forearm muscle oxygenation, parameters associated with oxidative metabolism, and microvascular reactivity as well as brachial artery endothelial function. Forearm skeletal muscle parameters were assessed in 12 healthy young men (26 ± 6 yrs) using near-infrared spectroscopy (NIRS) combined with a 5-min vascular occlusion test. Additionally, brachial artery endothelial function was simultaneously assessed by measuring the relative change in brachial artery diameter normalized to the hyperemic blood flow (Normalized %FMD). These measurements were performed before and after the RM interventions performed on the anterior forearm muscles. Forearm muscle oxygenation increased after 30 s of RM (62 ± 7 to 71 ± 11%; p = 0.02) while there was no change from baseline to post-intervention after 2 min of RM. No change was observed for oxidative metabolism, however, the significant main effect (p = 0.02) for NIRS-derived reperfusion slope (%·s−1) indicated that microvascular function improved after both 30 s (2.30 ± 0.5 to 2.61 ± 0.70%·s−1) and 2 min of RM (2.33 ± 0.4 to 2.60 ± 0.85%·s−1). The lack of significant effects of RM on Normalized %FMD suggest that the RM did not acutely improve brachial artery endothelial function. These findings provide, for the first time, evidence that RM improves skeletal muscle oxygenation and parameters associated with microvascular reactivity. Additionally, RM increased brachial artery blood flow, but not upstream brachial artery endothelial function.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Old cells die hard - sympatholysis and the ageing erythrocyte.

Vascular And Blood Flow Responses To Upper Limb Exercise In Individuals With Posttraumatic Stress Disorder

The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. Peripheral vascular dysfunction may be a mechanism by which PTSD increases CVD risk. PURPOSE: This study sought to determine if blood flow regulation and peripheral vascular function are altered during exercise in individuals PTSD when compared to age-matched controls. METHODS: Sixteen individuals with PTSD (10 women, 6 men; age 24 ± 4 years), and twenty-four age, and sex-matched healthy controls (CTRL); 15 women, 9 men, 24 ± 4 years), participated in the study. Upper limb vascular function and blood flow was assessed during rhythmic, progressive handgrip exercise (at rest, 3 and 6 kilograms (kg)) with Doppler ultrasonography. Exercise-induced changes in mean arterial pressure (MAP), brachial artery (BA) flow mediated dilation (normalized for BA shear rate), BA blood flow, and arm vascular conductance (VC) were quantified at each workload. RESULTS: Although no significance was noted in MAP, BA flow mediated dilation, or blood flow between groups, the PTSD group reported significantly lower VC at the highest exercise workload (6 kg - PTSD: 2.04 ± 0.9; CTRL: 2.87 ± 1.0 mL·min−1·mmHg−1; p = 0.008), when compared to the CTRL group. CONCLUSION: This study revealed that individuals with PTSD reported lower vascular conductance during upper limb arm exercise when compared to healthy controls. Further research is needed to determine if this finding translates to larger muscle mass exercise, potentially leading to exercise intolerance, as well as the potential mechanisms may be driving this dysfunction in individuals with PTSD, such augmented sympathetic activity during exercise and/or microvascular dysfunction.

696-P: Vasodilatory Response of the Muscular Artery Was Improved to Sheer Stress, but Paradoxically Decreased to Endothelium-Dependent Vasodilator in Diet and Aerobic Exercise in Type 2 Diabetes

The aims of this study were to investigate whether the stiffness of large elastic artery such as aorta and the muscular artery such as brachial artery improves through lifestyle modifications in type 2 diabetes. Total 82 overweight women with type 2 diabetes (age 55.0±7.6 years) were randomly assigned to control (C), diet (D), aerobic exercise (AE) and resistance exercise (RE) and completed the weight loss program for 12 weeks. We assessed BMI, augmentation index (AI) of aorta and also the flow-mediated dilation (FMD), the right brachial artery blood flow responses to an endothelium-independent vasodilator(ED), acetylcholine,, and an endothelium-dependent vasodilator(EID), isosorbide dinitrate, adiponectin/leptin ratio(ALR), free fatty acid(FFA), hsCRP, and insulin sensitivity (KITT) at baseline, and 12 week. There was no change in AI despite significant decreases in BMI in all intervention groups. FMD increased only in D and AE, but ED decreased in all 3 groups. EID increased only in D. The vascular function to sheer stress improved in muscular artery, not in large elastic artery with lifestyle changes. The response to isosorbide dinitrate was not consistent with FMD. Disclosure K. Han: None. B. Yang: None. K. Min: None.

P1315PREDICTABILITY OF SONOGRAPHICALLY DETERMINED IMMEDIATE POST-OPERATIVE BLOODFLOW AND VEIN DIAMETER ON PRIMARY RADIOCEPHALIC FISTULA SHORT AND LONGTERM OUTCOMES

Abstract Background and Aims Vascular access (VA) guidelines recommend radio-cephalic (RC) over upper arm autogenous arteriovenous fistulas (AVF) as first line VA for hemodialysis in end stage renal disease (ESRD) patients. RCAVFs generally have inferior maturation and patency rates predicated on a lower feeding arterial blood flow (BF) and outflow vein calibre (VC). However studies on postoperative BF and VC as predictors of AVF outcomes, so far are confounded by their focus on early outcomes only, heterogeneity of AVFs studied, variable timing of assessment and use of non-standardised outcome definitions. Our aim was therefore to assess the accuracy and influence of immediate post-operative BF and VC on both early and longterm outcomes in a homogenous cohort of primary RCAVFs using standardised definitions and outcome measures as mandated by VA guidelines. Method This was a prospective study conducted in multi-ethnic Asian ESRD patients who had their primary RCAVFs created between October 2013 and October 2014 under regional anesthesia at Khoo Teck Puat hospital Singapore. All AVFs were assessed immediately after surgery for brachial artery BF and outflow VC using doppler ultrasound. A 10MHz linear probe and GE Logic e R7 machine were used exclusively by a single operator. Receiver operating characteristic (ROC) curves were generated to determine the optimal BF and VC cut-off for AVF maturation. Maturation was defined as BF&amp;gt;600mL/min, VC&amp;gt;6mm and vein depth &amp;lt;6mm at 6 weeks post-op. An area under the curve (AUC)&amp;gt; 0.7 was considered clinically significant. Kaplan–Meier analysis was used to evaluate the AVF primary and secondary patency based on best BF and VC cut-offs. Cox regression statistics was used to determine AVF hazard factors. Results Fifty-seven primary RCAVFs were created and included in the study. The baseline characteristics are shown in Table 1. Sonography- based non-assisted maturation at 6 weeks was 56%. ROC identified 410 mL/min and 42mm as the best BF and VC cut-off respectively to most accurately predict 6-week maturation. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 61%, 44% and 86% for BF at 410 mL/min and 69%, 61%, 41% and 83% for VC at 42mm respectively. Survival analysis (Fig. 1 and 2) showed that AVFs with VC≥42 mm compared to &amp;lt;42mm had significantly greater 6 months, 1-year, 2-year and 4-year primary and secondary patency rates. There was no significant difference in patency rates between AVFs with BF≥410 and &amp;lt;410mL/min. Cox proportional regression hazard analysis showed that diabetes (HR 2.26, CI 1.02-4.99, p= 0.04) and maturation (HR 0.47, 95% CJ 0.24-0.89, p=0.02) as significant contributed to the variability of primary patency. Only VC (HR 0.28, 95% CI 0.13-0.063, p=0.002) impacted significantly towards secondary patency. Conclusion An immediate post-op BF≥410mL/min and VC≥42mm can predict early RCAVF outcome in the form of nonassisted maturation, but only VC accurately impact on longterm AVF survival. VA surveillance efforts should therefore target RCAVFs with post-op VC &amp;lt;42mm for timely intervention and maintenance of longterm patency.

New Zealand Blackcurrant Extract Enhances Muscle Oxygenation During Forearm Exercise in Intermediate-Level Rock Climbers

The delivery to and utilization of oxygenated hemoglobin to the forearm muscles are key determinants of rock-climbing performance. Anthocyanin-rich New Zealand blackcurrant (NZBC) has been suggested to improve blood flow and may enhance forearm endurance performance. As such, a double-blind, randomized crossover design study with 12 participants performed submaximal intermittent contractions (at 40% maximal voluntary contraction) to failure after a 7-day intake of 600mg/day NZBC extract or placebo. Minimum tissue saturation index (TSI%) was assessed during the contractions. During recovery, time to half recovery of TSI% and brachial artery blood flow were assessed. There was no difference in time to exhaustion between NZBC and placebo. Minimum TSI% was lower with NZBC extract (43 ± 8 vs. 50 ± 11 TSI%; p = .007; Cohen's d = 1.01). During recovery, there was no effect on brachial artery blood flow. However, time to half recovery was faster with NZBC (26 ± 17 vs. 42 ± 26s; p = .001; Cohen's d = 1.3) following exhaustive contractions. Seven days of NZBC extract appears to improve muscle oxygenation during and following contractions with no change in either arterial blood flow or forearm endurance performance.

Effect of sinusoidal leg cycling exercise period on brachial artery blood flow dynamics in humans

PurposeTo quantify the dynamics of blood flow in brachial artery (BF-BA) in response to sinusoidal work rate (WR) leg cycling exercises of 2-, 4-, and 6-min periods and to examine their relationship with the forearm skin blood flow (SBF).MethodsSeven healthy young male subjects performed upright leg ergometer exercise with a constant WR (mean sinusoidal WR) for 30 min followed by sinusoidal WR exercise of three different periods (number of repetitions): 2 min (7), 4 min (4), and 6 min (3). The WR fluctuated from 20 W to a peak WR corresponding to 60% peak oxygen uptake (VO2). We continuously measured pulmonary gas exchange, heart rate (HR), blood velocity and cross-sectional area of BA, and forearm SBF and sweating rate (SR).ResultsAll variables were followed by the sinusoidal WR. The phases of the variables for gas exchange and central circulation, such as VO2 and HR with WR forcing were similar (e.g., phase shift (θ) in HR [°]: 2 min, 60 ± 7; 4 min, 45 ± 10; 6 min, 37 ± 8; mean ± SD) to previous study results, that is, a longer period showed a shorter θ and larger amplitude of responses. Contrarily, the BF-BA response showed anti-phase (approximately 180°) regardless of the period, whereas the θ of forearm SBF and SR were similar to gas exchange and central circulation.ConclusionsInactive limb BF-BA during sinusoidal leg cycling exercise was out of phase relative to the regulation of O2-delivery to active muscles and thermoregulation. The response of BF-BA seems to not always reflect the response of forearm SBF in the downstream area.

Limb blood flow and muscle oxygenation responses to rhythmic exercise below and above critical force

This study aimed to determine brachial artery blood flow (Q̇BA) and microvascular oxygen delivery responses to rhythmic exercise above and below critical force (CF; the isometric analog of critical power). We hypothesized that Q̇BA, deoxygenated‐heme (deoxy‐[heme]; an estimate of microvascular fractional oxygen extraction), and total‐heme concentrations (total‐[heme]; an estimate of changes in microvascular hematocrit) would demonstrate physiological maximums above CF despite increases in exercise intensity. 13 healthy subjects performed 1) a 5‐min rhythmic isometric‐handgrip maximal‐effort test (MET) to determine CF and 2) constant target‐force tests above (severe‐intensity; S1 and S2) and below (heavy‐intensity; H1 and H2) CF. CF was 189.3 ± 16.7 N (29.7 ± 1.6 %MVC). At end‐exercise, Q̇BA was greater during S1 (418 ± 147 mL/min) and S2 (403 ± 137 mL/min) than during H1 (287 ± 97 mL/min) and H2 (340 ± 116 mL/min; p &lt; 0.05) but was not different between S1 and S2. Further, Q̇BA for S1 and S2 were not significantly different from the Q̇BA estimated for CF (392 ± 37 mL/min). At end‐exercise, deoxy‐[heme] was not different between S1 (150 ± 50 μM) and S2 (155 ± 57 μM), but was greater during S1 and S2 than during H1 (101 ± 24 μM) and H2 (111 ± 21 μM; p &lt; 0.05). Total‐[heme] was not different between S1 (404 ± 58 μM) and S2 (397 ± 73 μM), but was greater during S1 and S2 than H1 (352 ± 58 μM; p &lt; 0.01) but not H2 (371 ± 57 μM). These data suggest limb blood flow limitations and maximal levels of muscle microvascular oxygen delivery and extraction during exercise above, but not below, CF.End‐exercise brachial artery blood flow (Q̇BA) values. Q̇BA at end‐exercise below (● H1 and ○ H2) and above (▼ S1 and Δ S2) critical force (CF), and Q̇BA predicted at CF by linear regression (♦). * Significantly greater than Q̇BA at end‐exercise during H1 (p &lt; 0.05). ** Significantly greater than Q̇BA at end‐exercise during H2 (p &lt; 0.05). Note no differences among end‐exercise Q̇BA values at (estimated) and above CF, suggesting a maximal response in the severe‐intensity domain.Figure 1Frequency‐domain near‐infrared spectroscopy (FD‐NIRS) measurements of muscle oxygenation during exercise below (● H1 and ○ H2) and above (▼ S1 and Δ S2) critical force (CF). Dashed lines indicate average endexercise values of respective FD‐NIRS signals during the maximal‐effort test (MET). * Significantly different from end‐exercise during H1 and H2 (p &lt; 0.05). ** Significantly greater than total‐[heme] at end‐exercise during H2 (p &lt; 0.05).Figure 2

Autoantibody Subtype does not Impact Peripheral Endothelial Function and Hemodynamics in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular dysfunction that leads to vasculopathy and fibrosis. Autoantibody assessment is included as part of the diagnostic criteria and has implications for organ‐involvement and disease. The purpose of this study was to assess peripheral endothelial function and hemodynamics across a range of autoantibody subtypes among patients with SSc. We hypothesized that endothelial function would differ between autoantibody subtypes, with greater dysfunction in the more severe autoantibody subtype (i.e., topoisomerase; SCL70). To our knowledge, this is the first study with an adequate sample size with endothelial function measurements in several autoantibody subtypes. Patients that met ACR/EULAR SSc classification criteria were enrolled at a single center. Endothelial function was assessed in study subjects with the flow‐mediated dilation (FMD) technique using a 5‐min suprasystolic occlusion period and following published guidelines. A blood pressure cuff was placed on the right arm, distal to the ultrasound Doppler probe on the brachial artery. Simultaneous measurements of brachial artery vessel diameter and blood velocity were performed using a linear array transducer operating in duplex mode. The brachial artery was insonated approximately midway between the antecubital and axillary regions, and measurements of diameter and blood velocity were obtained continuously at rest and for 2 minutes after cuff deflation. To determine autoantibody status, patient blood samples were collected, and an antigen‐specific enzyme‐linked immunosorbent assay (ELISA) was performed. One‐way ANOVA was used to determine the variance between groups. Patients with SSc (n=139) were matched for age and disease duration, then grouped by autoantibody status (centromere, topoisomerase, RNA polymerase III, other SSc‐associated autoantibodies, and anti‐nuclear antibody positive, but with no known autoantibody present). In this cohort of patients with SSc, basic clinical characteristics did not differ between autoantibody groups (p&gt;0.05). Baseline brachial artery diameter and blood flow were similar across autoantibody groups (p=0.43 and p=0.82, respectively). Post‐ischemic peak reactive hyperemia and total hyperemia were not different between autoantibody groups (p=0.84 and p=0.99, respectively). There was no difference in absolute % FMD (p=0.11), and this similarity persisted with normalization to the shear rate at peak dilation (p=0.34). We observed no difference in peripheral endothelial function or hemodynamics (i.e., hyperemia and shear) based on autoantibody status. Thus, these data suggest that autoantibody status does not differentially affect peripheral endothelial function and hemodynamics in patients with SSc.Support or Funding InformationFunding Information: Funded in part by NIH R01 AG048366, R01 AG050238, R01 AG060395, K99 AT010017, US Department of Veteran Affairs I01 CX001183

Improved Vascular Function Following 7 days of L‐Citrulline Administration in Heart Failure with Preserved Ejection Fraction

BackgroundThere is increasing evidence to support the presence of peripheral vascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF), which may be due, at least in part, to disease‐related changes in nitric oxide (NO) signaling. L‐Arginine (L‐Arg) is the sole substrate for NO synthesis, but is susceptible to intestinal and hepatic degradation via arginase when administered orally. L‐Citrulline (L‐Cit) is catabolized to L‐Arg at the tissue level and is not a substrate for arginase, and therefore enteral L‐Cit administration has emerged as an effective approach for increasing NO substrate bioavailability.PurposeThe present investigation sought to determine whether oral L‐Cit administration (6g/day for 7 days) would improve vascular function in patients with HFpEF.MethodsIn 13 patients NYHA Class II (n=9) and III (n=4) with HFpEF (2M/11F, 69±10y, EF: 66±7%), flow mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit artery and microvascular function, respectively. FMD was expressed as % change in brachial artery diameter (%FMD) and % change corrected for shear rate (%FMD/shear), and RH was calculated as area‐under‐the‐curve for brachial artery blood flow. Plasma L‐Cit and L‐Arg concentrations were assessed to confirm absorption and evaluate circulating NO substrate, and the ratio of L‐Arg to plasma asymmetric dimethylarginine (ADMA) was calculated as a biomarker of NO bioavailability.ResultsCompared to baseline, L‐Cit administration improved FMD (0d: 2.5 ± 0.5%, 7d: 4.7 ± 0.9%), FMD/shear (0d: 0.07 ± 0.02, 7d: 0.12 ± 0.01AU) and RH (0d: 450 ± 46ml, 7d: 574 ± 62ml). L‐Cit (0d: 42 ± 3μM/L, 7d: 370 ± 60 μM/L), L‐Arg (0d: 65 ± 8μM/L, 7d: 257 ± 25μM/L), and L‐Arg:ADMA (0d: 136 ± 14AU, 7d: 481 ± 50AU) all increased following L‐Cit administration.ConclusionsThis study has identified the efficacy of a 7d administration of L‐Cit to improve NO substrate bioavailability, the L‐Arg/ADMA ratio, and both conduit artery and microvascular function in patients with HFpEF. These results provide new insight into the mechanisms that govern peripheral vascular dysfunction in this patient group, and demonstrate a promising plasticity in the peripheral vasculature among patients with this chronic disease.Support or Funding InformationSupport or Funding Information: This project is funded in part by the National Institutes of Health (HL118313; D.W.W., R56AG057584; R.S.R., T32HL139451 R.S.R) and the U.S. Department of Veterans Affairs (I01RX001311; D.W.W., I01RX001697; R.S.R., I01RX002323; R.S.R., I21RX001433; R.S.R., I01RX000182; R.S.R.) and the American Heart Association (18POST33960192; K.B.).