Flow-mediated Dilation Response Research Articles

Blood flow simulation during flow‐mediated dilation

AbstractEndothelial dysfunction is known to be the early stage of arteriosclerosis. The flow‐mediated dilation (FMD) test is the most commonly used method to diagnose the endothelial function. The test measures the maximum vasodilation (FMD response) on the brachial artery induced by the increases in blood flow after cuff deflation on the forearm. The vessel diameter must be captured clearly with the ultrasonic probe during the test. The vasodilation is induced in response to changes in the mechanical property of the vessel wall due to the blood flow stimulation. The changes are supposed to affect the pulsatile flow, but the influence of continuous behavior of vascular property on hemodynamics has not been clarified. In this study, in order to clarify the influence of the FMD response on hemodynamics, we propose a mathematical model that can simulate hemodynamics and vasomotor responses. As a result, it was shown that vessel wall dynamics affected the pulsatile flow. This result suggests that the endothelial function can be evaluated from blood flow.

Blood pressure predicts endothelial function and the effects of ethinyl estradiol exposure in young women.

Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18-35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78-91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95-113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18-31%, n = 8; obese: 38-59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not. NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.

Influence of fitness and age on the endothelial response to acute inflammation.

What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P<0.05). The YA (low fit, from 11.5±1.8 to 9.2±1.3%; moderately fit, from 11.9±0.8 to 9.0±0.8%) and moderately fit OA (from 7.5±1.0 to 3.9±0.8%) had similar reductions in FMD at 24h (P<0.05). Low-fit OA did not reduce FMD at 24h (from 5.5±0.4 to 5.2±0.5%, P>0.05). The reduction in FMD in YA was similar between fitness groups (P>0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. The augmentation index and carotid elastic modulus did not change during acute inflammation. In conclusion, in OA, higher fitness is associated with a greater decrease in endothelial function during acute inflammation, and this response is similar to that of young adults. This suggests that moderately fit OA may maintain vascular reactivity in response to stress, indicating preserved vascular function in moderately fit versus low-fit OA.

Brachial artery endothelial function is unchanged after acute sprint interval exercise in sedentary men and women.

What is the central question of this study? What is the acute brachial artery endothelial function response to sprint interval exercise and are there sex-based differences? What is the main finding and its importance? Brachial artery endothelial function did not change in either men or women following an acute session of SIT consisting of 3×20s 'all-out' cycling sprints. Our findings suggest this low-volume protocol may not be sufficient to induce functional changes in the brachial artery of sedentary, but otherwise healthy adults. Sprint interval training (SIT) is a potent metabolic stimulus, but studies examining its acute effects on brachial artery endothelial function are limited. The influence of oestradiol on the acute arterial response to this type of exercise is also unknown. We investigated the brachial artery endothelial function response to a single session of SIT in sedentary healthy men (n=8; 22±4years) and premenopausal women tested in the mid-follicular phase of the menstrual cycle (n=8; 21±3years). Participants performed 3×20s 'all-out' cycling sprints interspersed with 2min of active recovery. Brachial artery flow-mediated dilatation (FMD) and haemodynamic parameters were measured before and 1 and 24h post-exercise. Despite attenuations in some haemodynamic parameters at 1 h post-exercise, there were no changes in absolute (P=0.23), relative (P=0.23) or allometrically scaled FMD (P=0.38) following a single session of SIT. Resting and peak dilatory diameters did not change in men or women (P>0.05 for all) and there were no interactions between time and sex for any measure (P>0.05). Oestradiol was not correlated with relative FMD at baseline (r=-0.22, P=0.42) or with the change in relative FMD from baseline to 1h post-exercise (r=0.24, P=0.40). Overall, brachial artery FMD appears to be unchanged in men and women following an acute session of SIT, and the higher oestradiol concentrations in women do not augment the baseline or post-exercise FMD response. The 3×20s model of low-volume sprint interval exercise may not be sufficient to alter brachial artery endothelial function in healthy men and women.

Brachial Artery FMD Responses To Steady-State Moderate-Intensity And High-Intensity Interval Exercise In Mid-Spectrum Chronic Kidney Disease

Brachial artery flow-mediated dilation (FMD) is a nitric oxide-dependent measure of conduit artery endothelial function that is transiently potentiated by moderate-intensity steady-state exercise (SSE) in healthy adults. Whether exercise imparts similar effects in adults with Stage 3 or 4 chronic kidney disease (CKD) has not been reported. Moreover, a comparison of SSE and high-intensity interval exercise (HIIE) may add to clinically-relevant findings for improving vascular function in mid-spectrum CKD. PURPOSE: To determine the influence of SSE and a comparable amount of HIIE on post-exercise brachial artery FMD in patients diagnosed with secondary Stage 3 or 4 CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Ultrasound measurements of brachial artery FMD were obtained by the same technician under standardized conditions just before, 1 hr and 24 hrs after exercise. FMD responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs. RESULTS: Brachial artery FMD responses were augmented 1 hr after exercise in both exercise conditions (p < 0.005 versus pre-exercise FMD). SSE (pre-exercise = 11.5 + 1.3; 1 hr = 17.2* + 1.8; 24 hr = 14.0* + 1.1%) HIIE (pre-exercise = 12.5 + 1.3; 1 hr = 15.6* + 1.5; 24 hr = 15.8* + 1.2%) SUMMARY: We report for the first time that brachial artery FMD can be augmented by a single episode of exercise in mid-spectrum CKD. SSE and HIIE, averaging ~65% of VO2reserve, is equally effective at transiently improving conduit artery vascular function in this clinical population.

Influence of Sex and Exercise Intensity on Acute Flow‐Mediated Dilation Response to Aerobic Exercise in Healthy Young Adults

Brachial artery flow‐mediated dilation (FMD), a measure of endothelial function, is an independent predictor of future cardiovascular events. Sex and exercise intensity influence the acute FMD response to aerobic exercise in older adults, but in young adults this has not been investigated. Therefore, the purpose of this study was to compare the acute FMD response to a single bout of high‐intensity interval training (HIIT), moderate‐intensity continuous training (MICT) and low‐intensity continuous training (LICT) in young men vs. women. Twenty‐eight healthy young adults (14 men and 14 premenopausal women, 21.2±0.3 vs. 21.5±0.8 years of age, means ± SE, P =0.7) participated in this randomized crossover study. Brachial artery FMD was measured in response to reactive hyperemia following 5‐min forearm occlusion using high resolution ultrasonography. FMD measures were obtained prior to exercise, at the end of a single bout of HIIT (40 min, 4 × 4‐min intervals at 90% peak heart rate (HRpeak), MICT (47 min, 70% HRpeak) and LICT (47 min, 50% HRpeak) on the treadmill and following 60‐min recovery from exercise. The acute FMD response was influenced by exercise intensity but not sex (P=0.006 for exercise intensity × time and P=0.9 for sex × exercise intensity × time), thus the results are presented for men and women combined. FMD was attenuated by 20.7% following the end of HIIT (6.96±0.51 vs. 5.47±0.48%, pre‐ vs. end of exercise; P=0.001) and returned to pre‐exercise levels following 60‐min recovery (P&gt;0.99). However, FMD did not change in response to MICT(7.10±0.53 vs. 6.32±0.57 vs. 7.26±0.37%; P≥0.3) and LICT (7.14±0.41 vs. 7.46±0.56 vs. 7.15±0.43%; P&gt;0.99). In conclusion, exercise intensity, but not sex, significantly impacts the acute FMD response to aerobic exercise in young adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein

To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58), p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = - 7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5, p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.

Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction

ABSTRACTEndothelial dysfunction is a surrogate marker of cardiovascular risk. Resveratrol is known to improve endothelial function in animals, however, clinical trials are limited. We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction. Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a randomized, cross-over, double-blind, placebo-controlled trial. Individuals received either a single dose of trans-resveratrol (300 mg) or placebo and were crossed-over after a one-week washout period. Blood pressure (BP) measurements, aortic systolic blood pressure (SBP) and brachial flow-mediated dilation (FMD) were performed before and 1.5 hours after the intervention. FMD was significantly increased in women (4.2 ± 0.5 vs 7.1 ± 1.3%, p = 0.026) but not in men (4.4 ± 0.9 vs 4.9 ± 0.8%, p = 0.588) in the trans-resveratrol group. There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP. Patients with higher low-density lipoprotein (LDL) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol (7.4 ± 1.2 vs 4.3 ± 1.0%, p = 0.004). Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function, especially in women and those with higher LDL-cholesterol, despite no changes in BP.List of Abbreviation: Aix: augmentation index; AP: augmentation pressure; BP: blood pressure; BMI: body Mass Index; CVD: cardiovascular disease; FMD: flow-mediated dilation; FRS: Framingham Risk Score; HDL: high-density lipoprotein; LDL: low-density lipoprotein; NO: nitric oxide; SPSS: Statistical Package for Social Sciences; ROS: reactive oxygen species; SBP: systolic blood pressure; TG: triglycerides.

Brachial flow-mediated dilatation response to acute different upper body training postures in lean inactive vs. lean active men

BackgroundResistance training postures trigger different results on endothelial function: however, the acute effect of resistance training on upper body muscle in active and inactive persons is inconclusive. The present study aimed to investigate the acute effects of 2 different types of upper body training (bench press training and lat pull down training) on flow-mediated dilation (FMD), and to compare the effects between lean inactive men (LI) and lean active men (LA). MethodsLI (n = 16) and LA (n = 16) men undertook 2 upper body training postures at 60% of 1 repetition maximum (RM), 15 repetitions a set for 3 sets. Before and after immediate training, the biological data, FMD data, and blood pressure data were collected. ResultsBoth the LI and LA groups showed similar results at the baseline of biological data, including carotid intima media thickness data (P > 0.05), while the higher muscular strength was observed in the LA group. Significantly higher shear rate and blood pressure after training were observed in both groups (P < 0.05); however the magnitude of increment in blood pressure was greater in LI group. FMD was significantly increased in the LA group following bench press training while it decreased in the LI group following lat pull down training (P < 0.05). ConclusionHigher fitness status can acutely protect against the undesirable effects on vascular function following resistance training. In active persons, we suggest performing both the bench press and lat pull down trainings, without any limitations. In contrast for inactive persons, the bench press is recommended at the beginning of training for protection against decreased FMD. After vascular adaptation, lat pull down training might be added in order to strengthen upper body muscles.

The impact of menstrual phase on brachial artery flow-mediated dilatation during handgrip exercise in healthy premenopausal women.

What is the central question of this study? The aim of this study was to determine the influence of menstrual phase on flow-mediated dilatation in response to sustained, exercise-induced increases in shear stress. What is the main finding and its importance? We showed, for the first time, that in healthy, premenopausal women the flow-mediated dilatation stimulated by exercise-induced increases in shear stress did not fluctuate across two phases of the menstrual cycle, despite significant fluctuations in oestrogen. This suggests that endothelial function is not consistently augmented in the high-oestrogen phase. Flow-mediated dilatation (FMD) in response to a sustained shear-stress stimulus (e.g. via handgrip exercise; HGEX) is emerging as a useful tool for assessing endothelial function; however, the impact of menstrual phase on HGEX-FMD is unknown. The purpose of this study was to determine whether HGEX-FMD fluctuates with cyclical changes in oestrogen concentrations over two discrete phases (low and high oestrogen) of the menstrual cycle. Brachial artery (BA) diameter and blood velocity were assessed with two-dimesional and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR=BA blood velocity/BA diameter). Participants (12 healthy, regularly cycling women, 21±2years of age) completed two experimental visits: (i) low oestrogen (early follicular, EF); and (ii) high oestrogen (late follicular, LF). Reactive hyperaemia-stimulated FMD (RH-FMD) and HGEX-FMD (6min of handgrip exercise) were assessed during each visit. Results are mean values±SD. Oestrogen increased from the EF to LF phase (EF, 33±9pgml-1 ; LF, 161±113pgml-1 , P=0.003). However, neither the SR stimuli (HGEX, P=0.501; RH, P=0.173) nor the FMD responses differed between phases (EF versus LF: HGEX-FMD, 4.8±2.8 versus 4.6±2.2%, P=0.601; RH-FMD, 7.9±4.3 versus 6.4±3.1%, P=0.071). These results extend existing RH-FMD findings indicating that not all women experience fluctuations in FMD with the menstrual cycle. Further research is needed to investigate the mechanisms that underlie variability in the impact of menstrual phase on FMD.

Acute glucoregulatory and vascular outcomes of three strategies for interrupting prolonged sitting time in postmenopausal women: A pilot, laboratory-based, randomized, controlled, 4-condition, 4-period crossover trial.

BackgroundProlonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear.MethodsIn preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size.ResultsNine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033).ConclusionThis study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed.Trial registrationClinicalTrials.gov NCT02743286.

Effects of acute exercise on endothelial function in patients with abdominal aortic aneurysm.

Endothelial dysfunction is observed in patients with abdominal aortic aneurysm (AAA), who have increased risk of cardiovascular events and mortality. This study aimed to assess the acute effects of moderate- and higher-intensity exercise on endothelial function, as assessed by flow-mediated dilation (FMD), in AAA patients (74 ± 6 yr old, n = 22) and healthy adults (72 ± 5 yr old, n = 22). Participants undertook three randomized visits, including moderate-intensity continuous exercise [40% peak power output (PPO)], higher-intensity interval exercise (70% PPO), and a no-exercise control. Brachial artery FMD was assessed at baseline and at 10 and 60 min after each condition. Baseline FMD was lower [by 1.10% (95% confidence interval: 0.72-.81), P = 0.044] in AAA patients than in healthy adults. There were no group differences in FMD responses after each condition ( P = 0.397). FMD did not change after no-exercise control but increased by 1.21% (95% confidence interval: 0.69-1.73, P < 0.001) 10 min after moderate-intensity continuous exercise in both groups and returned to baseline after 60 min. Conversely, FMD decreased by 0.93% (95% confidence interval: 0.41-1.44, P < 0.001) 10 min after higher-intensity interval exercise in both groups and remained decreased after 60 min. We found that the acute response of endothelial function to exercise is intensity-dependent and similar between AAA patients and healthy adults. Our findings provide evidence that regular exercise may improve vascular function in AAA patients, as it does in healthy adults. Improved FMD after moderate-intensity exercise may provide short-term benefit. Whether the decrease in FMD after higher-intensity exercise represents an additional risk and/or a greater stimulus for vascular adaptation remains to be elucidated. NEW & NOTEWORTHY Abdominal aortic aneurysm patients have vascular dysfunction. We observed a short-term increase in vascular function after moderate-intensity exercise. Conversely, higher-intensity exercise induced a prolonged reduction in vascular function, which may be associated with both short-term increases in cardiovascular risk and signaling for longer-term vascular adaptation in abdominal aortic aneurysm patients.

PP.20.01] REPRODUCIBILITY OF DIFFERENT MEASURES OF ENDOTHELIAL FUNCTION

Objective: Brachial artery flow-mediated dilatation (FMD) to determine endothelial function is an investigator-demanding method. Impaired endothelial function as measured by FMD is known to be associated with cardiovascular risk factors. Local thermal hyperaemia (LTH) of the skin measured with a laser Doppler flow imager is less demanding and may serve as an alternative. We investigated the reproducibility of LTH and its correlation with FMD. In addition, the association of FMD with post-occlusive dermal hyperaemia (PORH), a widely used measure of microvascular function, was assessed. Design and method: FMD, LTH and PORH were measured in 27 healthy men (8 smokers) on two occasions, one week apart, at the same time of the day. FMD, measured with ultra-sound, was expressed as the maximal percentage increase in brachial artery diameter during reactive hyperaemia. LTH peak was defined as the maximal dermal blood flow (DBF) response within the first ten minutes and LTH plateau as the average DBF response during the last five minutes of 35 heating in arbitrary units (a.u.), measured with a laser Doppler flow imager. PORH Peak and AUC were measured at the volar site of the left forearm just under the pressure cuff, using a laser speckle imager. Results: Coefficients of variation (n = 27) of the LTH peak and plateau response were 18% and 21%, of the PORH peak and area under the curve (AUC) response both 13% and of the FMD response 21%. The LTH peak and plateau response and FMD response were not correlated, whereas the PORH AUC was correlated with FMD (r = 0.46, p < 0.05) and PORH Peak correlated with LTH Plateau (r = 0.58, p < 0.05). Conclusions: The reproducibility of the LTH plateau response and FMD response were almost equal in this study. In addition, as LTH and FMD did not correlate, these responses appear to provide different information. PORH, however, correlated partly with both LTH and FMD and should be further investigated as a possible alternative for FMD in long-term outcome studies.

Impaired flow-mediated dilation response and carotid intima-media thickness in patients with type 1 diabetes mellitus with a mean disease duration of 4.1 years.

This study aimed at assessing the endothelial function in patients with Type 1 diabetes (T1DM) using flow-mediated dilation (FMD) response and carotid artery intima-media thickness (CIMT). This study enrolled 32 T1DM patients (mean disease duration 4.1 years) and 28 age-matched controls (CTL Group). Endothelial function and CIMT were assessed with high-resolution ultrasound using standardized offline measurements. FMD was significantly lower in patients in the T1DM Group (8.9 ± 3.2%) compared with those in the CTL Group (13.3 ± 4.3%; P-value < 0.0001). Similarly, CIMT differed significantly between T1DM patients (0.525 ± 0.03 mm) and controls (0.508 ± 0.03 mm; P-value = 0.041). Even though, the values are within the normal range for age. Patients with T1DM have impaired endothelial function characterized by reduced FMD when compared to controls. However, vascular remodeling as seen by increases in CIMT was not found in this study.

The influence of vitamin C on the interaction between acute mental stress and endothelial function.

To determine whether orally administered vitamin C attenuates expected mental stress-induced reductions in brachial artery endothelial function as measured by flow-mediated dilation (FMD). Fifteen men (21±2years) were given 1000mg of vitamin C or placebo over two visits in a randomized, double-blinded, within-subject design. Acute mental stress was induced using the Trier Social Stress Test (TSST). Saliva samples for cortisol determination and FMD measures were obtained at baseline, pre-TSST, and 30 and 90-min post-TSST. An additional saliva sample was obtained immediately post-TSST. Cardiovascular stress reactivity was characterized by changes in heart rate (HR) and mean arterial pressure (MAP). A significant stress response was elicited by the TSST in both conditions [MAP, HR, and salivary cortisol increased (p<0.001)]. Overall FMD did not differ pre- vs. post-stress (time: p=0.631) and there was no effect of vitamin C (condition: p=0.792) (interaction between time and condition, p=0.573). However, there was a correlation between cortisol reactivity and changes in FMD from pre- to post-stress in the placebo condition (r 2=0.66, p<0.001) that was abolished in the vitamin C condition (r 2=0.02, p=0.612). Acute mental stress did not impair endothelial function, and vitamin C disrupted the relationship between cortisol reactivity and changes in FMD post-stress. This suggests that acute mental stress does not universally impair endothelial function and that reactive oxygen species signaling may influence the interaction between FMD and stress responses.

Reduced reactive hyperemia may explain impaired flow-mediated dilation after on-pump cardiac surgery.

In previous studies, Flow Mediated Dilation (FMD) was used to study the effect of cardiac surgery on endothelial function. This study investigated the effect of on‐pump cardiac surgery on FMD and reactive hyperemia. The FMD‐response and reactive hyperemia were measured in 25 patients the morning before‐ and the first morning after cardiac surgery. Brachial artery diameter and blood flow were measured with ultrasound at baseline before 5 min occlusion of the blood flow to the forearm, and continuously for 3 min after release of the occlusion. An exponential wash‐out model was fitted to the blood flow over time. Nineteen patients remained for final data analysis. Data are mean ± SEM. The FMD response was reduced after surgery from 3.3 ± 0.5% to 1.4 ± 0.6% (P = 0.02). Max blood flow after cuff release was reduced from 342 ± 30 mL preoperatively to 305 ± 30 mL postoperatively (P < 0.00) and fell toward baseline significantly quicker; preoperative half‐life was 36 ± 2.4 sec. versus 29 ± 1.9 sec postoperatively (P < 0.00). Resting blood flow was reduced from 84 ± 9 mL/min to 66 ± 9 mL/min, (P < 0.00). Brachial artery baseline diameter was unaffected by coronary artery bypass surgery (P = 0.3). The observed reduction in brachial artery FMD after surgery, by previous authors taken to represent endothelial dysfunction, may at least partly be due to reduced hyperemic flow postoperatively. In studies where FMD is measured on multiple occasions, flow data should also be included. Reduced postoperative blood flow to the arm may indicate regional differences in vascular resistance after cardiac surgery.

Effects of Prior Aerobic Exercise on Flow Mediated Dilation Responses to Prolonged Sitting in Healthy Men

Effects of Prior Aerobic Exercise on Flow Mediated Dilation Responses to Prolonged Sitting in Healthy Men

Assessment of flow-mediated dilatation in the superficial femoral artery using a sustained shear stress stimulus via calf plantar-flexion exercise.

What is the central question of this study? The aim was to establish the ability of a newly designed leg exercise technique to produce sustained elevations in shear rate that stimulate flow-mediated dilatation (FMD) in the superficial femoral artery and to determine the repeat trial stability of the FMD response. What is the main finding and its importance? Calf plantar-flexion exercise can be used to increase shear stress and stimulate FMD in the superficial femoral artery. However, the magnitude of FMD varied systematically when multiple trials were repeated in short succession. The superficial femoral artery (SFA) is susceptible to vascular disease, and a technique to assess flow-mediated dilatation (FMD) in this vessel in response to a sustained shear stress stimulus could provide important information about endothelial function. The aim of this study was to establish the ability of a newly designed SFA leg exercise-FMD (LEX-FMD) technique to produce sustained elevations in shear rate, which stimulate FMD, and to determine the repeat trial stability of the FMD response. The SFA FMD stimulated by reactive hyperaemia (RH) and calf plantar-flexion exercise (LEX) was assessed via ultrasound in 19 healthy men (n=10) and women (n=9). The two experimental visits included either four trials of LEX-FMD or four trials of RH-FMD. The shear stress stimulus was estimated as the shear rate (blood velocity/SFA diameter). Results are expressed as the means±SD. The LEX steady-state shear rate was consistent between trials (P=0.176), whereas the RH shear rate area under the curve was higher in trial 1versus trials 2-4 (P<0.05). The %RH-FMD (four-trial mean 4.9±2.5%) and absolute RH-FMD were not significantly different between trials (P=0.465 and P=0.359, respectively). Both %LEX-FMD and absolute LEX-FMD were higher during trial 3 (4.8±3.4%) than trial 1 (3.6±2.7%; P=0.026 and P=0.026, respectively). The magnitude of RH-FMD and LEX-FMD did not differ (P=0.241). These results indicate that calf plantar-flexion exercise can be used to increase shear stress and stimulate FMD in the SFA. However, although SFA RH-FMD was stable across four trials, LEX-FMD varied systematically when multiple trials were repeated in rapid succession.

Cardiorespiratory fitness modulates the acute flow-mediated dilation response following high-intensity but not moderate-intensity exercise in elderly men.

Impaired endothelial function is observed with aging and in those with low cardiorespiratory fitness (V̇o2peak). Improvements in endothelial function with exercise training are somewhat dependent on the intensity of exercise. While the acute stimulus for this improvement is not completely understood, it may, in part, be due to the flow-mediated dilation (FMD) response to acute exercise. We examined the hypothesis that exercise intensity alters the brachial (systemic) FMD response in elderly men and is modulated by V̇o2peak Forty-seven elderly men were stratified into lower (V̇o2peak = 24.3 ± 2.9 ml·kg-1·min-1; n = 27) and higher fit groups (V̇o2peak = 35.4 ± 5.5 ml·kg-1·min-1; n = 20) after a test of cycling peak power output (PPO). In randomized order, participants undertook moderate-intensity continuous exercise (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO) or no-exercise control. Brachial FMD was assessed at rest and 10 and 60 min after exercise. FMD increased after MICE in both groups {increase of 0.86% [95% confidence interval (CI), 0.17-1.56], P = 0.01} and normalized after 60 min. In the lower fit group, FMD was reduced after HIIE [reduction of 0.85% (95% CI, 0.12-1.58), P = 0.02] and remained decreased at 60 min. In the higher fit group, FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52% (95% CI, 0.41-2.62), P < 0.01, which was correlated with V̇o2peak, r = 0.41; P < 0.01]. In the no-exercise control, FMD was reduced in both groups after 60 min (P = 0.05). Exercise intensity alters the acute FMD response in elderly men and V̇o2peak modulates the FMD response following HIIE but not MICE. The sustained decrease in FMD in the lower fit group following HIIE may represent a signal for vascular adaptation or endothelial fatigue.NEW & NOTEWORTHY This study is the first to show that moderate-intensity continuous cycling exercise increased flow-mediated dilation (FMD) transiently before normalization of FMD after 1 h, irrespective of cardiorespiratory fitness level in elderly men. Interestingly, we show increased FMD after high-intensity cycling exercise in higher fit men, with a sustained reduction in FMD in lower fit men. The prolonged reduction in FMD after high-intensity cycling exercise may be associated with future vascular adaptation but may also reflect a period of increased cardiovascular risk in lower fit elderly men.

Sex impacts the flow-mediated dilation response to acute aerobic exercise in older adults

There is growing evidence of sex differences in the chronic effect of aerobic exercise on endothelial function (flow-mediated dilation; FMD) in older adults, but whether there are sex differences also in the acute effect of aerobic exercise on FMD in older adults is unknown. The purpose of this study was to test the hypothesis that sex modulates the FMD response to acute aerobic exercise in older adults. Thirteen older men and fifteen postmenopausal women (67±1 vs. 65±2years, means±SE, P=0.6), non-smokers, free of major clinical disease, participated in this randomized crossover study. Brachial artery FMD was measured: 1) prior to exercise; 2) 20min after a single bout of high-intensity interval training (HIIT; 40min; 4×4 intervals 90% peak heart rate (HRpeak)), moderate-intensity continuous training (MICT; 47min 70% HRpeak) and low-intensity continuous training (LICT; 47min 50% HRpeak) on treadmill; and 3) following 60-min recovery from exercise. In older men, FMD was attenuated by 45% following HIIT (5.95±0.85 vs. 3.27±0.52%, P=0.003) and by 37% following MICT (5.97±0.87 vs. 3.73±0.47%, P=0.03; P=0.9 for FMD response to HIIT vs. MICT) and was normalized following 60-min recovery (P=0.99). In postmenopausal women, FMD did not significantly change in response to HIIT (4.93±0.55 vs. 6.31±0.57%, P=0.14) and MICT (5.32±0.62 vs. 5.60±0.68%, P=0.99). In response to LICT, FMD did not change in postmenopausal women nor older men (5.21±0.64 vs. 6.02±0.73%, P=0.7 and 5.70±0.80 vs. 5.55±0.67%, P=0.99). In conclusion, sex and exercise intensity influence the FMD response to acute aerobic exercise in older adults.