Assessment of Endothelial Reactivity by Measurement of Vascular Material Response to Shear Stress: A Feasibility Study.

Flow-mediated dilation (FMD) evaluates the relative change in arterial diameter during hyperemia to assess the endothelial response due to a shear stimulus. However, conventional FMD measures diameter response alone and the alterations in the arterial wall's material properties during reactive hyperemia, which also influence dilation, go unaddressed. In this work, we examine the material response (MR) of the artery during reactive hyperemia using clinically relevant stiffness markers for the assessment of endothelial reactivity (ER). For this, we have developed an in-house brachial cuff control (BCC) system to continuously acquire brachial pressure which can be integrated with simultaneous measurement of brachial diameter and used to quantify the relative changes in wall property during hyperemia non-invasively. The assessment of endothelial reactivity using material response (ERAMR) was conducted on 20 healthy participants (12M/8F) and the results were compared with conventional FMD (FMD%). The mean pressure response gave an inverse trend to that of diameter response with varying magnitudes during reactive hyperemia (18.71% from baseline for diameter and 2.45% for pressure), there was a significant difference in the measurement of FMD and ERAMR (P < 0.05). The larger distribution of ERAMR compared to FMD% in box-plots further implies the inclusion of within-subject variations. Hence, ERAMR can be a potential estimate of ER, given the need for intensive validations in this line on larger cohorts.Clinical Relevance- This study demonstrates the independent role of arterial wall material properties to quantify endothelial reactivity in response to a shear stimulus.

Flow-mediated slowing shows poor repeatability compared with flow-mediated dilation in non-invasive assessment of brachial artery endothelial function.

Pulse wave velocity (PWV) deceleration to reactive hyperemia-flow-mediated slowing (FMS)-has been suggested as an alternative method to flow-mediated dilation (FMD) to evaluate brachial artery endothelial function. FMS is suggested to address major caveats of the FMD procedure including its suboptimal repeatability and high-operator dependency. However, the repeatability of FMS has not been thoroughly examined, especially given the plethora of methods claiming to measure PWV. We assessed and compared the intra- and inter-day repeatability of FMS as measured by piezoelectric pressure mechanotransducers placed in the carotid and radial arteries, and brachial artery FMD as measured by echo-tracking. Twenty-four healthy male participants aged 23-75 yr, were examined on three separate days to assess intra and inter-day repeatability. All FMD and FMS examinations were conducted simultaneously by the same researcher complying with standardized guidelines. Repeatability was examined with intraclass correlation coefficient (ICC; >0.80), coefficient of variation (CV; <15%), and limits of agreement (95% LOA). Relative (%) FMD and FMS were scaled for baseline brachial artery diameter and PWV, respectively. Intra- (ICC: 0.72; CV: 136%; 95% LOA: -19.38 to 29.19%) and Inter-day (ICC: 0.69; CV: 145%, 95% LOA: -49.50 to 46.08%) repeatability of %FMS was poor, whereas %FMD demonstrated moderate-to-good intra- (ICC: 0.93; CV: 18%, 95% LOA: -3.02 to 3.75%) and inter-day repeatability (ICC: 0.74; CV: 25%, 95% LOA: -9.16 to 7.04%). Scaling FMD reduced the intra-day CV (-5%), and the uncertainty of the 95% LOA (- 37.64 to 35.69%) estimates of FMS. Carotid-radial artery FMS showed poorer repeatability compared to FMD.

[The role of endothelial dysfunction for assessment of a rehab potential in the patients with acute stroke]. / Rol' endotelial'noi disfunktsii dlya otsenki reabilitatsionnogo potentsiala u patsientov v ostrom periode ishemicheskogo insul'ta.

OBJECTIVE: The analysis of the endothelial reactivity in the acute stroke by it severity and determination of rehab potential. MATERIALS AND METHODS: Twenty-three patients with ischemic stroke, aged 50 to 80 years, who were treated in the regional vascular center of Omsk region, were studied. The severity of stroke and stroke outcome was assessed by NIHSS and the modified Rankin scale. The test with reactive hyperemia was performed for all patients with measurement of the diameter of the brachial artery by ultrasonic diagnostics. RESULTS: Endothelial reaction that was investigated in the postischemic vasodilatation test depends on the severity of stroke and neurological deficiency. Moreover, endothelial dysfunction with bad outcome appears on the 7th day after stroke. CONCLUSION: The method can be used for evaluation of rehab potential.

A novel method for the noninvasive estimation of cardiac output with brachial oscillometric blood pressure measurements through an assessment of arterial compliance.

OBJECTIVE: To propose and validate a new method for estimating cardiac output based on the total arterial compliance (Ct) formula that does not need an arterial waveform and to apply it to brachial oscillometric blood pressure measurements (OBPMs). METHODS: One hundred subjects with normal heart anatomy and function were included. Reference values for cardiac output were measured with echocardiography, and Ct was calculated with a two-element Windkessel model. Then, a statistical model of arterial compliance (Ce) was used to estimate cardiac output. Finally, the measured and estimated cardiac output values were compared for accuracy and reproducibility. RESULTS: The model was derived from the data of 70 subjects and prospectively tested with the data from the remaining 30 individuals. The mean age of the whole group was 43.4 ± 12.8 years, with 46% women. The average blood pressure (BP) was 107.1/65.0 ± 15.0/9.6 mmHg and the average heart rate was 67.7 ± 11.4 beats/min. The average Ct was 1.39 ± 0.27 mL/mmHg and the average cardiac output was 5.5 ± 1.0 L/min. The mean difference in the cardiac output estimated by the proposed methodology vs. that measured by Doppler echocardiography was 0.022 L/min with an SD of 0.626 L/min. The intraclass correlation coefficient was 0.93, and the percentage error was 19%. CONCLUSION: Cardiac output could be reliably and noninvasively obtained with brachial OBPMs through a novel method for estimating Ct without the need for an arterial waveform. The new method could identify hemodynamic factors that explain BP values in an ambulatory care setting.

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.

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

BACKGROUND AND AIMS: Recent 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. METHODS: We 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). RESULTS: As 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). CONCLUSIONS: Our 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.

Improving the Assessment of Flow-Mediated Dilation Through Detection of Peak Time in Healthy Subjects and Subjects With Type 2 Diabetes.

The assessment of flow-mediated dilation (FMD) is widely used to quantify endothelial function. Historically, FMD was determined at 60 seconds post-cuff deflation. We investigated whether FMD would be more accurate if determined at maximum dilatory peak (MDP) than at 60 seconds in healthy subjects and subjects with type 2 diabetes mellitus (T2DM). We studied 95 healthy and 72 subjects with T2DM and assessed FMD at MDP, 60 and 90 seconds. Twenty-four healthy and 12 subjects with T2DM underwent a repeat FMD after 28 days. In healthy subjects, FMD at MDP was higher than at 60 and 90 seconds, with mean difference MDP versus 60 seconds 1.14% (95% CI: 0.6-1.7); P < .0001 and MDP versus 90 seconds 1.9% (95% CI: 1.3-2.5) with similar results in T2DM, that is, 1.0% (95% CI: 0.1-1.9) and 2.3% (95% CI: 1.3-3.2), respectively. Intraindividual variability was lowest with MDP compared with 60 and 90 seconds, that is, 15.0 versus 23.2% and 40.0%, respectively, resulting in a more than 2-fold reduction in necessary sample size. In healthy subjects and subjects with T2DM, assessment of FMD using MDP results in a more accurate and precise assessment leading to a substantial reduction in sample size.

Ultrasound Based Computational Fluid Dynamics Assessment of Brachial Artery Wall Shear Stress in Preeclamptic Pregnancy.

PURPOSE: Preeclampsia (PE) is a pregnancy complication of abnormally elevated blood pressure and organ damage where endothelial function is impaired. Wall shear stress (WSS) strongly effects endothelial cell morphology and function but in PE the WSS values are unknown. WSS calculations from ultrasound inaccurately assume cylindrical arteries and patient specific computational fluid dynamics (CFD) typically require time-consuming 3D imaging such as CT or MRI. METHODS: Two-dimensional (2D) B-mode ultrasound images were lofted together to create simplified three-dimensional (3D) geometries of the brachial artery (BA) that incorporate artery curvature and non-circular cross sections. This process was efficient and on average took 120 ± 10 s. Patient specific CFD was then performed to quantify BA WSS for a small cohort of PE (n = 5) and normotensive pregnant patients (n = 5) and compared against WSS calculations assuming a cylindrical artery. RESULTS: For several WSS metrics (time averaged WSS (TAWSS), peak systolic WSS, oscillatory shear index (OSI), OSI/TAWSS and relative residence time) CFD on the simplified arterial geometries calculated large spatial differences in WSS that assuming a cylindrical artery cannot calculate. Bland-Altman and intra-class correlation (ICC) analyses found assuming a cylindrical artery both underestimated (p < 0.05) and had poor agreement (ICC < 0.5) with the maximum WSS values from CFD. WSS values that were abnormal compared to the normotensive patients (OSI = 0.014 ± 0.026) appear related to the pregnancy complications fetal growth restriction (n = 2, OSI = 0.14, 0.25) and gestational diabetes (n = 1, OSI = 0.23). CONCLUSION: Creating 3D artery geometries from 2D ultrasound images can be used for CFD simulations to calculate WSS from ultrasound without assuming cylindrical arteries. This approach requires minimal time for both medical imaging and CFD analysis.

Assessment of Atherosclerosis in Peripheral and Central Circulation in Adult ß Thalassemia Intermedia Patients by Color Doppler Ultrasound: Egyptian Experience.

BACKGROUND: Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in ß thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis. AIM: In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in ß TI patients. METHODS: For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries' (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls. RESULTS: Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV. CONCLUSION: More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients.

Assessment of intima-media thickness of the carotid artery and intraluminal diameter of the brachial artery as cardiovascular risk markers in Brazilian adolescents with overweight or obesity.

Background The intima-media thickness of the carotid artery (cIMT) and endothelial dysfunction are associated with cardiovascular (CV) disease. Objectives To evaluate the correlation between cIMT, brachial intraluminal diameter and flow-mediated vasodilation on the reactive hyperemia phase in adolescents with obesity with predictors of CV risk. Methods Seventy-three pubertal patients with overweight or obesity were evaluated (45 girls) with a mean (standard deviation [SD]) age of 12.9 (2.5) years. Patients underwent anthropometric measurements and had the lipid profile, oral glucose tolerance test (oGTT) and serum intercellular adhesion molecule-1 (sICAM-1) levels analyzed. The ratios of the waist circumference (WC)/height (WHtR) and triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), homeostatic model assessment of insulin resistance (HOMA-IR), the Matsuda index and insulin area under the curve (AUC) were calculated. All patients were evaluated for cIMT and arterial blood flow velocity of the brachial artery. Results 75.3% of the patients had high cIMT values. We found a positive correlation between WHtR and cIMT (r = 0.233; p = 0.050). There was a positive correlation between sICAM-1 and insulin AUC (r = 0.323; p = 0.012) and WHtR (r = 0.258; p = 0.047). Patients with abnormal arterial dilation had higher sICAM-1 values (p = 0.02) despite having smaller WHtR (p = 0.046). Conclusions These adolescents with obesity had high cIMT values. Insulin resistance was associated with sICAM-1. Endothelial dysfunction was positively correlated with sICAM-1. There is no consensus about what the best laboratorial approach to evaluate insulin resistance in adolescents is, and the cutoff values of each method are arbitrary. So, as we saw earlier, the association between anthropometric data (WHtR) and ultrasound findings could be useful to evaluate the CV risk of these adolescents with obesity, because of its practical, direct and low-cost value.

New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study.

INTRODUCTION: Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. OBJECTIVES: The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. METHODS: A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). RESULTS: APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. CONCLUSIONS: This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

Assessment of brachial artery mechanics using velocity vector imaging does not predict arteriovenous fistula failure; a feasibility study.

Strain measurements by US have been suggested as a method of assessing arterial elasticity prior to arterio venous fistula creation. This pilot study sought to develop an imaging protocol to measure strain in the brachial artery via velocity vector imaging (VVI) and determine if differences in strain could be observed between a healthy group and a group with end-stage renal disease (ESRD), and if VVI measurements were associated with arterio-venous fistula malfunction. 40 healthy volunteers and 33 patients with ESRD were included in this study. All participants underwent US assessment of brachial artery strain via VVI. Peak velocity, strain, strain-rate and velocity were assessed. Patients with and without AVF failure at 3-months were assessed for differences in VVI measurement. Mean VVI measurements between the patient and volunteer groups were similar, and no significant differences were observed. Measurements were reproducible. No significant differences were observed in patients with or without AVF dysfunction. The results from this pilot study suggest VVI measurements of brachial artery mechanics are feasible and that VVI measurements may be used to assess age related changes of the brachial artery.

Shear-thinning behaviour of blood in response to active hyperaemia: Implications for the assessment of arterial shear stress-mediated dilatation.

NEW FINDINGS: What is the central question of this study? Quantitative values of shear rate-specific blood viscosity and shear stress in the human macrovasculature in response to exercise hyperaemia are unknown. What is the main finding and its importance? Using the handgrip exercise model, we showed that an increase in brachial artery shear rate led to a decrease in blood viscosity, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in brachial artery shear stress based on shear rate prediction. Our data yield new insights into the magnitude and regulation of macrovascular blood viscosity and shear stress in physiological conditions of elevated metabolic demand and blood flow in humans. ABSTRACT: Blood viscosity is a well-known determinant of shear stress and vascular resistance; however, accurate quantitative assessments of shear rate-specific blood viscosity in the macrovasculature in conditions of elevated blood flow are inherently difficult, owing to the shear-thinning behaviour of blood. Herein, 12 men performed graded rhythmic handgrip exercise at 20, 40, 60 and 80% of their maximal workload. Brachial artery shear rate and diameter were measured via high-resolution Duplex ultrasound. Blood was sampled serially from an i.v. cannula in the exercising arm for the assessment of blood viscosity (cone-plates viscometer). We measured ex vivo blood viscosity at 10 discrete shear rates within the physiological range documented for the brachial artery in basal and exercise conditions. Subsequently, the blood viscosity data were fitted with a two-phase exponential decay, facilitating interpolation of blood viscosity values corresponding to the ultrasound-derived shear rate. Brachial artery shear rate and shear stress increased in a stepwise manner with increasing exercise intensity, reaching peak values of 940 ± 245 s-1 and 3.68 ± 0.92 Pa, respectively. Conversely, brachial artery shear rate-specific blood viscosity decreased with respect to baseline values throughout all exercise intensities by ∼6-11%, reaching a minimal value of 3.92 ± 0.35 mPa s, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in shear stress based on shear rate prediction. Consequently, the use of shear stress yielded a higher slope for the brachial artery stimulus versus dilatation relationship than shear rate. Collectively, our data refute the use of shear rate to infer arterial shear stress-mediated processes.

Non-invasive vascular assessment in people with type 2 diabetes: Diagnostic performance of Plethysmographic-and-Doppler derived ankle brachial index, toe brachial index, and pulse volume wave analysis for detection of peripheral arterial disease.

OBJECTIVE: There is evidence that standard assessment techniques for detecting PAD might be of less diagnostic accuracy in people with type 2 diabetes. The aim of this study was to examine diagnostic performance of Plethysmographic-and-Doppler derived ankle brachial index, toe brachial index, and Pulse volume waveform analysis for detecting PAD in people with T2DM. METHODS: In this cross-sectional study 303 patients with T2DM were included in the study. The participants underwent ABI measurement, applying both Plethysmographic and Doppler derived devices, as well as TBI, PVW was also recorded for each patient. Diagnostic performance of each test for detecting PAD, applying ultrasound Doppler scan as the reference standard, was measured. Moreover, the best cut-off point for each method to detect PAD was determined. RESULTS: PVW showed the highest sensitivity (81.8%) for detecting PAD, followed by ABIDOP (72.7%), and ABIPLE (20%). However, all devices showed an excellent specificity for detecting PAD. The optimal cut-off point for diagnosis of PAD was 0.9 for ABIDOP, 1.2 for ABIPLE, and 0.38 for TBI. CONCLUSION: Within this population of patients with T2DM, TBI less than 0.38 provided the best sensitivity for detection of PAD followed by PVW, ABIDOP≤0.9, and ABIPLE<1.2.

Assessment of endothelial function is reproducible in patients with cystic fibrosis.

BACKGROUND: New treatments have improved life-expectancy in patients with cystic fibrosis (CF); however, cardiovascular health remains an area of concern in this population. Flow-mediated dilation (FMD), a non-invasive assessment of vascular endothelial function that predicts future cardiovascular disease and events, is attenuated in patients with CF compared to controls. The reproducibility of FMD in CF; however, has yet to be evaluated. Thus, this study sought to examine the within-day, between-day, and between-month reproducibility of FMD in patients with CF. METHODS: Pulmonary function, baseline diameter (cm), peak diameter (cm), and FMD(%) were assessed 5 times (sessions A-E) over four visits in 13 patients with CF (six males, seven females, age range: 13-43 years old; mean forced expiratory volume in 1 s = 71% predicted). Sessions A and B (within-day), C (between-day), and D and E (between-month) were separated by 3 h, at least 10 days, and ~3 months, respectively. Reproducibility was assessed by: (1) paired t-tests, (2) coefficients of variation (CV), (3) CV prime, (4) Pearson's correlation (r), (5) intra-class correlation coefficient, and (6) Bland-Altman plots. Five acceptable parameters were required to determine reproducibility. RESULTS: Pulmonary function was stable throughout all visits. FMD(%) and baseline diameter (cm) satisfied all six reproducibility criteria for within-day, while peak diameter (cm) met five of six criteria. All six reproducibility criteria were met for all between-day and between-month assessments. CONCLUSION: The present study provides evidence that endothelial function assessed by FMD is reproducible in patients with CF not only within-day, but also between-day and between-month.

The association between near-infrared spectroscopy-derived and flow-mediated dilation assessment of vascular responsiveness in the arm.

INTRODUCTION: Following a period of blood flow occlusion, the near-infrared spectroscopy (NIRS)-derived reperfusion slope of the oxygen saturation signal (StO2) is a measure of microvascular responsiveness that has been shown to be positively correlated with flow-mediated dilation (FMD) assessment of conduit artery function in the lower limb vasculature. Given that previously established differences in structure and function of the vessels in the upper compared to the lower limbs may change this relationship, investigating whether this correlation between the reperfusion slope of the StO2 and the FMD response is maintained in upper limbs is important. Accordingly, this study investigated the correlation between the reperfusion slope of the StO2 and FMD in the arm vasculature. METHODS: 18 physically active individuals were submitted to a vascular occlusion test (VOT). Microvascular responsiveness was calculated as the NIRS-derived reperfusion slope assessed in a forearm muscle. Macrovascular responsiveness was assessed at the brachial artery and calculated as a percent of change in FMD (%FMD). RESULTS: A statistically significant correlation (r = 0.66; P = 0.001) was found between the reperfusion slope and %FMD response. CONCLUSION: The significant correlation between the reperfusion slope in the forearm muscle and %FMD in the brachial artery, reinforces the relationship between downstream and upstream vascular reactivity in healthy human limbs.

New assessment of endothelial function measured by short time flow-mediated vasodilation: Comparison with conventional flow-mediated vasodilation measurement.

BACKGROUND: Measurement of flow-mediated vasodilation (FMD) is an established method for assessing endothelial function. Measurement of FMD is useful for showing the relationship between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implications including effects of interventions and cardiovascular events. To shorten and simplify the measurement of FMD, we have developed a novel technique named short time FMD (stFMD). We investigated the validity of stFMD for assessment of endothelial function compared with conventional FMD. METHODS AND RESULTS: We evaluated stFMD and conventional FMD in 82 subjects including patients with atherosclerotic risk factors and cardiovascular disease (66 men and 16 women, 57 ±â€¯16 years). Both stFMD and conventional FMD were significantly correlated with age, systolic blood pressure, diastolic blood pressure and baseline brachial artery diameter. In addition, stFMD was significantly correlated with conventional FMD (r = 0.76, P < 0.001). Bland-Altman plot analysis showed good agreement b etween stFMD and conventional FMD. Moreover, stFMD in the at risk group and that in the cardiovascular disease group were significantly lower than that in the no risk group (4.6 ±â€¯2.3% and 4.4 ±â€¯2.2% vs. 7.3 ±â€¯1.9%, P < 0.001, respectively). Optimal cutoff value of stFMD for diagnosing atherosclerosis was 7.0% (sensitivity of 71.0% and specificity of 85.0%). CONCLUSIONS: These findings suggest that measurement of stFMD, a novel and simple method, is useful for assessing endothelial function. Measurement of stFMD may be suitable for screening of atherosclerosis when repeated measurements of vascular function are required and when performing a clinical trial using a large population. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000025458.

Standardized Protocol for Hemodialysis Vascular Access Assessment: The Role of Ultrasound and ColorDoppler.

INTRODUCTION: Ultrasound and colorDoppler technique, which is relatively inexpensive, rapid, non-invasive and repeatable is a powerful tool used for early diagnosis of vascular access (VA) complications in hemodialysis patients. To date a standard and widely comprehensible echocolorDoppler (ECD) protocol is not available. MATERIALS AND METHODS: A simple step-by-step protocol based on anatomical and hemodynamic parameters of VA has been developed during a 3-years VA ECD follow-up. It consists of an ECD study scheme. The algorithm created involves the calculation of brachial artery flow, description of artero-venous and/or graft-vascular anastomosis and efferent vessel and/or graft. RESULTS: The algorithm allows to formulate a medical report that takes into account both anatomic and hemodynamic parameters of the VA. Reduction of complications and the prevention of chronic complications as well as the early detection of acute problems were achieved. DISCUSSION AND CONCLUSION: The creation of a step-by-step protocol may simplify the multidisciplinary management of VA, its monitoring and the early diagnosis of its complications.

Brachial Artery Wall Stiffness Assessment by Shear Wave Elastography: A Promising New Diagnostic Tool for Endothelial Dysfunction Detection.

OBJECTIVES: This study was designed to measure the changes in brachial artery wall stiffness by shear wave elastography (SWE) and evaluate the accuracy of SWE changes for detection of endothelial dysfunction. METHODS: Sixty-five consecutive participants (19 patients with atherosclerosis proven by coronary angiography, 16 healthy young adults, 15 patients with cardiovascular risk factors, and 15 healthy older adults between 50 and 60 years) were prospectively included in this study. They were examined in the same week by SWE, and flow-mediated dilatation was evaluated for each patient. RESULTS: The mean flow-mediated dilatation values ± 2 SDs after forearm occlusion were 8.54% ± 1.4% in healthy young adults, 7.61% ± 1.4% in healthy older adults, 5.83% ± 0.7% in patients with risk factors (P < .001), and 3.81% ± 2.4% in patients with atherosclerosis (P < .001, with respect to the risk factor group). There was a significant decrease in stiffness measurements in parallel with the increase in flow-mediated dilatation: 19.9% ± 6.3% in healthy young adults, 16.3% ± 5.1% in healthy older adults, 9.8% ± 5.4% in patients with risk factors (P < .05 with respect to the group with no risk factors), and 7.8% ± 6.4% in patients with atherosclerosis (P < .001 with respect to the healthy older adults). CONCLUSIONS: Shear wave elastography in combination with flow-mediated dilatation could be a promising, widely available noninvasive diagnostic tool for detecting endothelial dysfunction.

Reproducibility and agreement of different non-invasive methods of endothelial function assessment.

Flow-mediated dilatation (FMD) is an established, but investigator-demanding method, used to non-invasively determine nitric oxide (NO)-dependent endothelial function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a less demanding alternative of FMD. We investigated the reproducibility of the different measures of vascular function, their interrelationship and the NO-dependency of LTH. Measurements were performed twice in 27 healthy men (8 smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA) by means of iontophoresis was used to determine the NO-dependency of LTH. Using L-NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and 65% (<0.001), respectively. For all measurements the coefficient of variation (CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was 12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response 14% and of PORH area under the curve response 11%. FMD correlated weakly with the PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas the LTH-plateau response correlated with the PORH peak response (r = 0.68, p < .01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated to FMD. Furthermore, despite easy to perform the LTH responses are not more reproducible than FMD. Given the weak associations, the different methods of vascular function assessment are not interchangeable.