Flow-mediated Dilation Test Research Articles

Exposure-response modeling of flow-mediated dilation provides an unbiased and informative measure of endothelial function

The brachial artery flow-mediated dilation (FMD) test is the most widely utilized method to evaluate endothelial function noninvasively in humans by calculating the percent change in diameter (FMD%). However, the underutilized velocity and diameter time course data, coupled with confounding influences in shear exposure, noise, and upward bias, make the FMD test less desirable. In this study, we developed an exposure-response, model-based approach that not only quantifies FMD based on the rich velocity and diameter data, it overcomes previously acknowledged challenges. FMD data were obtained from 15 apparently healthy participants, each exposed to four different cuff occlusion durations. The velocity response following cuff release was described by an exponential model with two parameters defining peak velocity and rate of decay. Shear exposure derived from velocity was used to drive the diameter response model, which consists of additive constriction and dilation terms. Three parameters describing distinct aspects of the vascular response to shear (magnitude of the initial constriction response, and magnitude and time constant of the dilation response) were estimated for both the individuals and population. These parameters are independent of shear exposure. Thus this approach produces identifiable and physiologically meaningful parameters that may provide additional information for comparing differences between experimental groups or over time, and provides a means to completely account for shear exposure.NEW & NOTEWORTHY While flow-mediated dilation (FMD) is a valuable tool for evaluating endothelial function, analytical challenges include confounding influences of shear exposure, upward bias, and underutilization of rich time course data collected during FMD testing. We have developed an exposure-response, model-based approach that quantifies endothelial function based on the velocity and diameter data and fully accounts for shear exposure. It produces physiologically meaningful parameters that may provide useful information for comparing differences between experimental groups or over time.

Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity

The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome.

In individuals with atherosclerotic risk factors, endothelial dysfunction (ED) appears as an early phase in the development of clinical symptoms. Recent studies indicate that adropin, a newly identified peptide, participates in cardiovascular health through the regulation of several metabolic events including angiogenesis and blood flow. In this study, we aimed to determine the relation of adropin with biochemical and radiologic parameters which reflect ED such as endothelial nitric oxide synthase (eNOS), endothelin 1 (ET-1), nitric oxide (NO) and flow-mediated dilatation (FMD) along with the routine biochemical measurements in patients recently diagnosed with metabolic syndrome (MetS). Fasting blood samples from 110 patients with MetS diagnosed according to the NCEP ATP III-2005 criteria were collected to measure the concentrations of adropin and other parameters including the lipid profile, insulin and glucose. Serum NOx concentrations were determined by measuring NO2 plus NO3. FMD test was performed by ultrasonography, and patients were stratified as FMD (+) or (-). Data were compared between these two subgroups and also with matching healthy controls (n=50). Biochemical data were evaluated using Student's t or Mann-Whitney U tests. Fifty-nine subjects had ED (+) and the remaining 101 subjects were ED (-). In the first group, adropin levels were significantly lower than the latter (2.13±1.05 vs. 3.41±1.63 ng/mL, respectively; p<0.001) and independently associated with FMD positivity as assessed by the logistic regression analysis. Low adropin level in circulation is related to ED and has a close association with FMD. Any alterations in its level may be of help in order to assess the development of ED before the occurrence of clinical symptoms in patients with metabolic syndrome.

Feed-forward active contour analysis for improved brachial artery reactivity testing.

The object of this study was to utilize a novel feed-forward active contour (FFAC) algorithm to find a reproducible technique for analysis of brachial artery reactivity. Flow-mediated dilation (FMD) is an important marker of vascular endothelial function but has not been adopted for widespread clinical use given its technical limitations, including inter-observer variability and differences in technique across clinical sites. We developed a novel FFAC algorithm with the goal of validating a more reliable standard. Forty-six healthy volunteers underwent FMD measurement according to the standard technique. Ultrasound videos lasting 5-10 seconds each were obtained pre-cuff inflation and at minutes 1 through 5 post-cuff deflation in longitudinal and transverse views. Automated segmentation using the FFAC algorithm with initial boundary definition from three different observers was used to analyze the images to measure diameter/cross-sectional area over the cardiac cycle. The %FMD was calculated for average, minimum, and maximum diameters/areas. Using the FFAC algorithm, the population-specific coefficient of variation (CV) at end-diastole was 3.24% for transverse compared to 9.96% for longitudinal measurements; the subject-specific CV was 15.03% compared to 57.41%, respectively. For longitudinal measurements made via the conventional method, the population-specific CV was 4.77% and subject-specific CV was 117.79%. The intraclass correlation coefficient (ICC) for transverse measurements was 0.97 (95% CI: 0.95-0.98) compared to 0.90 (95% CI: 0.84-0.94) for longitudinal measurements with FFAC and 0.72 (95% CI: 0.51-0.84) for conventional measurements. In conclusion, transverse views using the novel FFAC method provide less inter-observer variability than traditional longitudinal views. Improved reproducibility may allow adoption of FMD testing in a clinical setting. The FFAC algorithm is a robust technique that should be evaluated further for its ability to replace the more limited conventional technique for measurement of FMD.

100 Longitudinal follow-up of endothelial function in pregnant women with chronic hypertension and normal blood pressure

Chronic arterial hypertension (CAH) is a condition that directly affects the prognosis of pregnancy by compromising the utero-placental perfusion and by increasing the incidence of cardiovascular events and other complications of pregnancy, particularly preeclampsia. Endothelial dysfunction caused by CAH is considered as one of the causes of those complications. Flow-mediated dilation (FMD) of the braquial artery is a biophysical marker of endothelial dysfunction. Compare endothelial function in pregnant women with CAH and in normotensive patients at two diferent times during the second trimester of gestation. A total of 18 hypertense and 22 normotense pregnant women were submitted to FMD of the brachial artery. The first examination was held between 16 and 20 weeks of gestation and the second between 24 and 28 weeks. When compared to normotense patients, the group of pregnant women with CAH presented lower FMD results between 16 and 20 weeks (3.65% × 5.43%, p = 0.022) and between 24 and 28 weeks (4.12% × 6.95%, p = 0.008). Endothelial dysfunction can be clinically detected by FMD test in the second trimester of pregnancy in women with CAH. This finding may help to elucidate the higher incidence of preeclampsia in these group of patients.

Repeatability of vascular responsiveness measures derived from near-infrared spectroscopy.

Near‐infrared spectroscopy (NIRS)‐derived measures of tissue oxygen saturation (StO2) have been recently shown to significantly correlate with the widely used method for noninvasively assessing vascular endothelial function, flow‐mediated dilation (FMD). The purpose of this study was to examine the intraday and interday reliability of the reperfusion slope of StO2 (slope 2 StO2) and compare it to FMD. Ultrasound‐derived FMD was quantified following 5 min of distal cuff occlusion of the popliteal artery in nine healthy young men (26 ± 3 years). An FMD test was performed each of 4 days, with a fifth involving three tests. FMD was calculated as the greatest percent change in diameter from baseline (%FMD). StO2 was measured using NIRS throughout each test, with slope 2 StO2 being calculated as the upslope of 10‐sec following cuff release. Reliability was determined using repeatability, intraclass correlation coefficients (ICC), and coefficient of variation (CV). Repeatability of slope 2 StO2 was better than %FMD for both intraday (0.43 and 5.65, respectively) and interday (0.48 and 4.82, respectively) comparisons; approximately 30% of mean values for slope 2 StO2 could be attributed to measurement error, whereas 100% of mean FMD could be for both intraday and interday comparisons. Similarly, ICC and CV values indicated stronger reliability of slope 2 StO2 compared to %FMD for both intraday (ICC 0.92 and 0.36, respectively; CV 9 ± 4% and 44 ± 24%, respectively) and interday (ICC 0.94 and 0.25, respectively; CV 14 ± 5% and 40 ± 22%, respectively) comparisons. In conclusion, NIRS‐derived slope 2 StO2 can be used as a reliable measure of vascular reactivity.

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies. Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events. Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test.

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies. Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events. Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

Effects of Eccentric Exercise‐Induced Muscle Damage on Endothelial Function and Skeletal Muscle Microvascular Deoxygenation

Unaccustomed eccentric exercise has been shown to result in muscle damage (EIMD) and to decrease maximal aerobic exercise capacity (VO2max). Central and peripheral cardiovascular function mediates VO2 max, but it is unclear whether alterations in endothelial and skeletal muscle microvascular function play a role in the reduced VO2 max seen after EIMD. We tested the hypotheses that EIMD of the knee extensors would: 1) decrease local (femoral artery) and systemic (brachial artery) endothelial‐dependent flow‐mediated dilation (FMD), 2) alter the near‐infrared spectroscopy (NIRS)‐derived muscle microvascular deoxygenation (Δ[HHb]) response during incremental cycling exercise, which reflects the balance between muscle O2 delivery and O2 utilization, and 3) decrease VO2max. To date, five of a planned fifteen participants have completed a brachial and femoral artery FMD test, an index of endothelial‐dependent dilation, followed by an incremental exercise test to exhaustion on a cycle ergometer during which pulmonary VO2 and changes in NIRS‐derived Δ[HHb] were measured. Δ[HHb] was measured in the m. vastus lateralis, was normalized to the total response, and was then expressed as a function of relative work rate and fit using a sigmoid function. Each test was performed prior to (Pre) and 48‐hr after a bout of knee extensor eccentric exercise designed to elicit localized muscle damage (Post). Pre brachial artery FMD was 9.7 ± 8.9% and Post brachial artery FMD was 3.6 ± 7.3% (P = 0.1, Effect size (ES) = 0.3). Pre femoral artery FMD was 7.9 ± 7.4% compared to a Post FMD of 1.0 ± 4.4% (P = 0.1, ES = 1.1). During exercise the sigmoid slope was 35.4 ± 25.6 %/% Pre and 37.9 ± 22.1 %/% Post (P = 0.8, ES = .1) Similarly, the c/d value (i.e., 50% of the amplitude of the Δ[HHb] response was 46.7 ± 102.0 % Pre compared to 36.6 ± 46.7 % Post (P = 0.7, ES = 0.1). Pre VO2max was 3.3 ± 0.64 l·min−1 while Post VO2max was 3.1 ± 0.76 l·min−1 (P = 0.1, ES = 0.3). To date this study is under powered (0.08) and additional participants will be tested and included in the final analysis. The findings from this study will provide insight into macro‐ and microvascular function following EIMD and their association with changes in VO2max.

Impaired handgrip exercise-induced brachial artery flow-mediated dilation in young obese males.

Flow mediated dilation (FMD) stimulated by different shear stress stimulus profiles may recruit distinct transduction mechanisms, and provide distinct information regarding endothelial function. The purpose of this study was to determine whether obesity influences brachial artery FMD differently depending on the shear stress profile used for FMD assessment. The FMD response to a brief, intermediate, and sustained shear stress profile was assessed in obese (n = 9) and lean (n = 19) young men as follows: brief stimulus, standard reactive hyperemia (RH) following a 5 min forearm occlusion (5 min RH); intermediate stimulus, RH following a 15 min forearm occlusion (15 min RH); sustained stimulus, 10 min of handgrip exercise (HGEX). Brachial artery diameter and mean shear stress were assessed using echo and Doppler ultrasound, respectively, during each FMD test. There was no group difference in HGEX shear stress (p = 0.390); however, the obese group had a lower HGEX-FMD (5.2 ± 3.0% versus 11.5 ± 4.4%, p < 0.001). There was no group difference in 5 min RH-FMD (p = 0.466) or 15 min RH-FMD (p = 0.181); however, the shear stress stimulus was larger in the obese group. After normalization to the stimulus the 15 min RH-FMD (p = 0.002), but not the 5 min RH-FMD (p = 0.118) was lower in the obese group. These data suggest that obesity may have a more pronounced impact on the endothelium's ability to respond to prolonged increases in shear stress.

Vascular responsiveness determined by near-infrared spectroscopy measures of oxygen saturation.

Vascular impairments at the macro- and microcirculatory levels are associated with increased risk for cardiovascular disease. Flow-mediated dilation (FMD) is currently the most widely used method for non-invasive assessment of vascular endothelial function. Recently, near-infrared spectroscopy (NIRS)-derived measures of tissue oxygen saturation (StO2) have been used to characterize the dynamic response of local tissue perfusion to a brief period of ischaemia. The purpose of the present study was to establish correlations between the reperfusion rate of StO2 and FMD. Ultrasound-derived FMD was quantified after 5 min of distal cuff occlusion of the popliteal artery in 20 healthy young men (26 ± 3 years old). Triplicate measurements of end-diastolic arterial diameter were made every 15 s after cuff release, and FMD response was calculated as the greatest percentage change in diameter from baseline (%FMD). The StO2 was measured using NIRS throughout the duration of each test. Two consecutive FMD tests were performed, separated by 30 min of rest, and were averaged for %FMD and StO2. The %FMD was significantly correlated with the reperfusion slope of StO2 after cuff release (slope 2 StO2; r = 0.63, P = 0.003). In conclusion, the present study established a correlation between slope 2 StO2 and %FMD in healthy young men. These data suggest that NIRS-derived slope 2 StO2 can be used as a measure of vascular endothelial function.

From sodium intake restriction to nitrate supplementation: Different measures with converging mechanistic pathways?

Endothelial nitric oxide synthase is at the centre of endothelial physiology producing nitric oxide which dilates blood vessels, inhibits platelet aggregation and smooth muscle cell proliferation and reduces adhesion molecule production. The laminar shear stress is a common test used usually as the flow mediated dilatation test (FMD) which is sensitive to saturated fat, sodium and potassium although with the latter ion it is possible potassium has direct effects on ion channels in the smooth muscle cell as well as the endothelial cell. High blood pressure and blood cholesterol both reduce nitric oxide production, the latter probably by increasing caveolin-1 which binds nitric oxide synthase. Saturated fat reduces nitric oxide by elevating LDL cholesterol and caveolin-1 while insulin stimulates nitric oxide synthase activity by serine phosphorylation. Polyphenols from tea, coffee and cocoa and virgin olive oil enhance FMD and eNOS activity is essential for this activity. Wine polyphenols produce mixed results and it is not clear at present that they are beneficial. Blackberries and other polyphenol-rich fruit also enhance FMD.Dietary nitrate from beetroot and green leafy vegetables is converted to nitrite by salivary microbes and then to nitric oxide and this acts directly on the smooth muscle to lower blood pressure particularly in a low oxygen environment. Dietary nitrate also improves work efficiency and improves flow mediated dilatation.

Flow mediated dilation with photoplethysmography as a substitute for ultrasonic imaging

Flow mediated dilation (FMD) is a non-invasive method for endothelial function assessment providing an index extracted from ultrasonic B-mode images. Although utilized in the research community, the difficulty of its application and high cost of ultrasonic devices prevent it from being widely used in clinical settings. In this study we show that substituting the ultrasonic device with more easily handled and low cost photoplethysmography and electrocardiography is possible. We introduce new indices based on the photoplethysmogram (PPG) and electrocardiogram (ECG) and show that they are correlated with the ultrasound-based FMD Index. To this end, a conventional ultrasound FMD test was carried out whereas PPG and ECG were simultaneously recorded from 20 healthy volunteers (13 M, 7 F) in the age range of 23–32 years. Our results show a significant correlation between our proposed index and ultrasound FMD when using the ECG in conjunction with the PPG (R = 0.77, p < 0.000 01). Using the PPG alone produces a lower correlation (R = 0.72, p < 0.0001). Compared to conventional FMD, the proposed method is low cost and does not require any special operator skills. Hence it may be easily utilized as a screening tool in locations deprived of high-end ultrasound imaging devices.

Carotid Artery IMT, Blood Pressure, and Fasted Glucose and Cholesterol Levels in Males and Females

Previous studies have investigated carotid artery intima‐media thickness (IMT) and blood pressure (BP) and found a direct correlation between the two. Also, studies have examined IMT and blood glucose and cholesterol levels. It is known that young adult females have better cardiovascular health than males. To the best of our knowledge, no prior study has investigated the carotid artery IMT, BP, and blood glucose/cholesterol levels in relation to gender differences in young healthy adults. On three separate days, 37 adults (25.35 ±10.9yrs; 22M, 15F) underwent carotid IMT ultrasound, flow‐mediated dilation (FMD), fasted glucose and cholesterol test, 24hr ambulatory BP monitoring, VO2max test, and body composition measurement (bioelectrical impedance). We found that females have lower systolic BP, lower LDL/HDL ratios, lower body mass index and a higher HDL count than males (p &lt; 0.01 for all), all of which are markers of increased cardiovascular health. However, we found no gender differences in vascular health measures, IMT and FMD (p &gt;0.05) Our results suggest that while adult females have better cardiovascular health than males, endothelial function may not yet be affected in the young adult years.

The effects of menstrual phase on brachial artery endothelial function after mental stress in young women

The changes in ovarian hormones throughout the menstrual cycle have direct actions on endothelial function. However, very limited human data are available regarding the alterations in endothelial function at baseline or after mental stress during the discrete phases of the menstrual cycle. We examined whether the menstrual cycle influences the endothelial function after mental stress in young women. Female university students were tested during three phases of a normal menstrual cycle. Delineation of the three phases occurred as follows: (1) the early follicular phase; (2) the late follicular phase; (3) the middle luteal phase. Non-invasive measurement of peripheral endothelial function was determined by flow-mediated dilation (FMD) testing in the brachial artery during reactive hyperemia using echo and Doppler ultrasound. After the measurements of basal levels, they were subjected to mental stress evoked by the modified Stroop Color Word Test (CWT) in 10 min. The CWT induced arterial pressure and heart rate (HR) elevations, and a slight vasoconstriction of brachial artery. The measurements of flow-mediated dilation (FMD) and maximal blood flow (%) were repeated at 5 min and 30 min after the CWT. Basal FMD and FMD after the CWT tended to vary during the three phases cyclically.These findings suggest the importance of menstrual phase in the interpretation of data on endothelial function.

Sildenafil Improves Flow‐Mediated Dilation in Adults with Cystic Fibrosis

Our group has provided evidence that endothelial function, assessed by the flow‐mediated dilation (FMD) test, is attenuated in patients with Cystic Fibrosis (CF) compared to healthy controls. The mechanisms for the dysfunction; however, have yet to be elucidated. Phosphodiesterase type 5 (PDE5) inhibitors have been shown to improve endothelial function in different patient populations, thus this study sought to determine if treatment with sildenafil improves FMD in patients with CF. To date we have recruited 4 adult patients with CF (2 men and 2 women; 35±4 years, mean FEV1 67±10 % predicted), 3 of whom have completed the protocol. Brachial artery FMD was performed at baseline and 4 weeks following treatment with sildenafil (20 mg, 3 x daily). Baseline brachial artery diameter increased (p=0.09) following 4 weeks of sildenafil (0.287 ± 0.04 cm to 0.296 ± 0.03 cm, respectively). FMD expressed as absolute change in diameter was significantly (p=0.04) improved from baseline (0.019 ±0.005 cm) to 4 weeks (0.026±0.006 cm), whereas relative FMD(%) was improved (p=0.09) following treatment (6.1±1.2% to 8.4±0.9%, respectively). No differences in shear rate (p=0.413) or time to peak dilation (p=0.463) were observed following treatment. Although the study has just begun, provocative preliminary findings suggest that 4 weeks of sildenafil can improve endothelial function in patients with cystic fibrosis. PDE5 inhibition may represent an adjunctive therapy to improve endothelial function in patients with CF. Supported by NIH/NIDDK R21DK100783 (RAH).

Alterations in endothelial function and fractional O2 extraction in long‐term cancer survivors treated with chemotherapy and radiation

Chemotherapy and radiation cancer therapeutics increase arterial stiffness and decrease aerobic exercise capacity. During exercise, the profile of microvascular fractional O2 extraction measured via near‐infrared spectroscopy (NIRS) derived muscle deoxygenation (Δdeoxy‐[Hb+Mb]) provides information on the dynamic matching of O2 delivery‐to‐O2 utilization. We tested the hypothesis that cancer survivors would have an altered profile of Δdeoxy‐[Hb+Mb] during exercise that would be related to decreases in endothelial function. To date, 2 cancer survivors (CS) and 1 healthy control (HC) completed a brachial artery flow‐mediated dilation test (FMD) and ramp exercise test on a cycle ergometer. During exercise Δdeoxy‐[Hb+Mb] of the vastus lateralis and rectus femoris was measured, normalized from baseline (0%) to the gas exchange threshold (GET) (100%). The power output at GET (POGET) was lower in CS compared to HC. CS had a smaller shear rate normalized FMD compared to HC (1.07 × 10‐5 vs. 3.54 × 10‐5 %Δ/s‐1 s, respectively). Both groups displayed a linear increase in %Δdeoxy‐[Hb+Mb]. The %Δdeoxy‐[Hb+Mb] slope of the vastus lateralis was greater in CS compared to HC when plotted as a function of POGET (2.04 vs. 0.80 % W‐1, respectively) and %POGET (1.84 vs. 1.17 % %W‐1, respectively). A greater %Δdeoxy‐[Hb+Mb] slope of the rectus femoris was also observed in CS compared to HC (1.29 vs. 0.74 % W‐1 and 1.17 vs. 1.09 % %W‐1, respectively). In conclusion, the greater reliance on fractional O2 extraction in CS during exercise suggests an impaired matching of O2 delivery‐to‐O2 utilization relationship during exercise compared to HC, which may be the result of decreased endothelial function.

Day‐to‐day Variability in Arterial Diameter and Brachial Artery Flow‐Mediated Dilation in Sedentary Young Men and Women

Brachial artery flow‐mediated dilation (FMD), an index of endothelial function, is predictive of cardiovascular disease risk. A wide range of FMD day‐to‐day variability has been reported, but whether this variability differs between men and women is unknown. We examined potential sex‐based differences in FMD and its day‐to‐day variability. Sedentary but otherwise healthy men (N=10, age: 22±3 years) and women (N=7, age: 21±2 years) completed two brachial FMD tests 24 hours apart. Women were tested during the mid‐follicular phase of their menstrual cycle (days 7‐12). Baseline arterial diameter (ADBL) and maximum reactive hyperemia diameter (ADRH) were determined, and relative FMD was calculated as FMD% = (ADRH–ADBL)/ADBL. Day 1 measures and between‐day differences were assessed with independent t‐tests. Day‐to‐day variability was assessed with the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Compared to men, women had smaller arterial diameters (p&lt;0.05), but a similar FMD response (p=0.828). No sex‐differences were observed in between‐day differences for any measures (p&gt;0.05). Day‐to‐day variability was low for AD in both sexes (CV of 3‐5%), but high for FMD (men: 43%, women: 55%). Similarly, ICCs were substantial to almost perfect for AD in both sexes (ICC of 0.77‐0.92), but poor for FMD (men: 0.01, women: 0.07). These findings suggest that arterial diameter exhibits better day‐to‐day repeatability than relative FMD in both men and women. Despite women having greater FMD variability than men, between‐day differences were not statistically significant. A larger sample size may be required to detect potential sex‐differences.Funded by NSERC, OGS and GSSI.

Impaired brachial artery endothelial function in young healthy women following an acute painful stimulus

Impaired endothelial function has been observed during and immediately following an acutely painful stimulus. However, the extent to which this persists following pain dissipation is unclear. To determine whether painful ischemic handgrip exercise (pain task) causes impaired flow-mediated dilation (FMD) after the sensation of pain and hemodynamic responses have abated. A second purpose was to determine whether the response to pain differed with a predisposition to magnify, ruminate, and feel helpless about pain (pain catastrophizing status). Brachial artery FMD stimulated by reactive hyperemia was assessed via ultrasound in 18 (9 high catastrophizing) healthy, women (20 ± 1 years) before and 15 min after a 3 min pain task. The shear stress stimulus for FMD was estimated as shear rate (blood velocity/brachial artery diameter). RESULTS (MEAN ± SD): None of the variables were significantly impacted by pain catastrophizing status and are presented pooled across group. The pain task increased pain ratings [1 ± 1-6 ± 3 (0-10 scale) (p < 0.001)], mean arterial pressure (MAP) (p < 0.001) and heart rate (HR) (p < 0.001), all returning to pre-pain levels ≤2-min post-pain task (pre-pain vs. 2-min post-pain: pain rating p = 1.000; MAP p = 0.142; HR p = 0.992). The shear rate stimulus was not different between pre- and post-pain task FMD tests (p = 0.200). FMD decreased post-pain task (10.8 ± 4.6 vs. 7.0 ± 2.7 %, p < 0.001). These results indicate that, regardless of pain catastrophizing status, painful ischemic handgrip exercise has a deleterious impact on endothelial function that persists after the pain sensation and hemodynamic responses have abated.

Differences in angiotensin (1–7) between men and women

In experimental animal models of hypertension, angiotensin (1-7) [ANG-(1-7)] is higher in females compared with males; however, it is less clear whether the same applies to humans. Therefore, this study sought to compare circulating concentrations of ANG-(1-7) in apparently healthy men and women under normal physiological conditions. With the use of a cross-sectional experimental design, blood was collected in EDTA anticoagulant from 42 volunteers (21 men and 21 women; and age range, 19-48 yr) for analysis of plasma concentrations of ANG-(1-7) and ANG II. Blood pressure was measured and vascular endothelial function was determined (n = 25) using the brachial artery flow-mediated dilation (FMD) test. As a result, women exhibited a higher circulating concentration of ANG-(1-7) (P = 0.04) compared with men, whereas values of ANG II were similar between groups. Baseline arterial diameter, peak diameter, and shear rate were significantly greater (P < 0.02) in men compared with women. No significant differences in FMD, FMD normalized for shear, or time to peak dilation were observed between men and women. In addition, a positive correlation between ANG-(1-7) and FMD (P = 0.04) and negative association between ANG-(1-7) with ANG II (P = 0.01) were only identified in men, whereas a positive relationship between ANG-(1-7) and diastolic blood pressure (P = 0.03) was observed in women. , women exhibit significantly higher plasma concentrations of ANG-(1-7) compared with men. In addition, this study describes a relationship between ANG-(1-7), vascular function, and diastolic blood pressure that appears to be sex dependent.