Reproducible improvement in endothelial function following two separate periods of high-intensity interval training in young men.

High-intensity interval training (HIIT) can improve vascular function, as assessed by brachial artery flow-mediated dilation (FMD). However, when separated by a period of detraining, the reproducibility of FMD responses to repeated periods of HIIT is unknown. The purpose of this study was to determine the group mean and intraindividual reproducibility of FMD responses to two 4-wk periods of HIIT, separated by 3 mo of detraining. Thirteen healthy, recreationally active men (21 ± 2 yr) completed the study. Each 4-wk HIIT period included 40 min of treadmill training four times/week. Each training session included four 7-min intervals: 4 min at 90%-95% heart rate maximum (HRmax) and 3 min at 70%-75% HRmax. Vascular (FMD) and cardiorespiratory fitness (maximal oxygen consumption [V̇o2max]) assessments were conducted before and following each 4-wk training period. Training resulted in significant improvements in V̇o2max (P < 0.001). Training also improved FMD (P < 0.001), with no differences between periods (P = 0.394), even after controlling for changes in baseline diameter and the shear rate stimulus. There was a significant, moderate relationship between the change in FMD in HIIT period 1 versus period 2 [R2 = 0.493, P = 0.011, intraclass correlation coefficient: 0.600, coefficient of variation: 17.3%]. Consecutive periods of HIIT separated by detraining resulted in similar improvements in FMD at the group level, and individual FMD changes in period 1 of HIIT predicted FMD changes in response to period 2. Considered alongside substantial between-participant variability in magnitude of FMD improvement, this suggests that there are reproducible, interindividual differences in the potential to improve vascular function with HIIT.NEW & NOTEWORTHY This is the first study examining endothelial function [flow-mediated dilation (FMD)] following repeated periods of high-intensity interval training (HIIT). Two periods of HIIT separated by detraining resulted in reproducible group-level improvements in FMD. Despite considerable between-subject variability in FMD adaptation, individual FMD changes with the first HIIT period predicted FMD changes in the second period. This indicates the existence of reproducible between-subject differences in susceptibility to FMD improvement with HIIT.

Thirty minutes of handgrip exercise potentiates flow-mediated dilatation in response to sustained and transient shear stress stimuli to a similar extent.

NEW FINDINGS: What is the central question of this study? This study sought to determine whether enhancement of brachial artery flow-mediated dilatation (FMD) after acute exposure to a sustained elevation in shear stress is greater when the shear stress stimulus for FMD is also sustained. What is the main finding and its importance? Brachial artery FMD in response to a sustained (handgrip exercise) and transient (reactive hyperaemia) shear stress stimulus was enhanced to a similar extent 10 min after a 30 min handgrip exercise intervention. This suggests that prior exposure to a sustained elevation in shear stress results in a similar acute augmentation of the ability of the endothelium to transduce sustained and transient shear stress stimuli. ABSTRACT: Brief (30 min) exposure of the brachial artery (BA) to a sustained elevation in shear stress has been shown to potentiate subsequent BA flow-mediated dilatation (FMD) in response to a transient shear stress stimulus [reactive hyperaemia (RH) FMD]. It is unknown whether matching the sustained shear stress exposure to a subsequent sustained shear stress stimulus for FMD [via handgrip exercise (SS-FMD)] might enhance the potentiation of FMD. The purpose of the study, therefore, was to assess the impact of a 30 min handgrip exercise intervention-induced elevation in shear stress on subsequent BA SS-FMD versus RH-FMD. Nineteen healthy men (22 ± 3 years) preformed a 30 min rhythmic handgrip exercise intervention on two experimental days. BA-FMD was assessed using either an RH or a 6 min sustained shear stress stimulus created via handgrip exercise (order of visits counterbalanced) at three time points: pre-intervention and 10 and 60 min post-intervention. The FMD was assessed using duplex ultrasound. Shear stress was estimated as shear rate (SR = BA blood velocity/BA diameter). Data are mean ± SD. Both SS and RH-FMD increased from pre-intervention to 10 min post-intervention [SS-FMD (6 min average), from 0.11 ± 0.05 to 0.16 ± 0.08 mm; P = 0.008; Cohen's d = 0.66; and RH-FMD, from 0.25 ± 0.1 to 0.32 ± 0.11 mm; P = 0.013; Cohen's d = 0.68]. The magnitude of enhancement in RH and SS-FMD did not differ (change in RH versus SS-FMD pre- versus 10 min post-intervention, P = 0.344). These findings suggest that exposure to elevated shear stress via 30 min of handgrip exercise potentiates subsequent FMD in response to sustained and transient elevations in shear stress to a similar extent.

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

NEW FINDINGS: 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 1 versus 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.

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

INTRODUCTION: 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. PURPOSE: 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). METHODS: 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). CONCLUSION: 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.

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress.

An inverse relationship between baseline artery diameter (BAD) and flow-mediated vasodilation (FMD) has been identified using reactive hyperemia (RH) to create a shear stress (SS) stimulus in human conduit arteries. However, RH creates a SS stimulus that is inversely related to BAD. The purpose of this study was to compare FMD in response to matched levels of SS in two differently sized upper limb arteries [brachial (BA) and radial (RA) artery]. With the use of exercise, three distinct, shear rate (SR) stimuli were created (SR = blood velocity/vessel diameter; estimate of SS) in the RA and BA. Artery diameter and mean blood velocity were assessed with echo and Doppler ultrasound in 15 healthy male subjects (19-25 yr). Data are means ± SE. Subjects performed 6 min of adductor pollicis and handgrip exercise to increase SR in the RA and BA, respectively. Exercise intensity was modulated to achieve uniformity in SR between arteries. The three distinct SR levels were as follows: steady-state exercise 39.8 ± 0.6, 57.3 ± 0.7, and 72.4 ± 1.2 s(-1) (P < 0.001). %FMD and AbsFMD (mm) at the end of exercise were greater in the RA vs. the BA at each shear level [at the highest level: RA = 15.7 ± 1.5%, BA = 5.4 ± 0.8% (P < 0.001)]. The mean slope of the within-subject SR-%FMD regression line was greater in the RA (RA = 0.33 ± 0.04, BA = 0.13 ± 0.02, P < 0.001), and a strong within-subjects relationship between %FMD and SR was observed in both arteries (RA: r(2) = 0.92 ± 0.02; BA: r(2) = 0.90 ± 0.03). Within the RA, there was a significant relationship between baseline diameter and %FMD; however, this relationship was not present in the BA (RA: r(2) = 0.76, P < 0.001; BA: r(2) = 0.03, P = 0.541). These findings suggest that the response to SS is not uniform across differently sized vessels, which is in agreement with previous studies.

Impact of repeated increases in shear stress via reactive hyperemia and handgrip exercise: no evidence of systematic changes in brachial artery FMD.

Reactive hyperemia (RH) creates an uncontrolled, transient increase in brachial artery (BA) shear stress (SS) for flow-mediated dilation (FMD) assessment. In contrast, handgrip exercise (HGEX) can create similar, sustained SS increases over repeated trials. The purpose of this study was to examine the impact of repeated SS elevation via RH or HGEX and the relationship between RH and HGEX %FMD. BA diameter and blood velocity were assessed with echo and Doppler ultrasound in 20 healthy subjects. Visit A consisted of four 6-min HGEX trials (HGEX trials 1-4) at the intensity required to achieve a shear rate (SR = mean blood velocity/BA diameter; an estimate of SS) of 65 s(-1). Visit B consisted of four RH trials (RH trials 1-4). The RH SR area under the curve (AUC) was higher in trial 1 versus trial 3 and trial 4 (P = 0.019 and 0.047). The HGEX mean SR was similar across trials (mean SR = 66.1 ± 5.8 s(-1), P = 0.152). There were no differences in %FMD across trials or tests (RH trial 1: 6.9 ± 3.5%, trial 2: 6.9 ± 2.3%, trial 3: 7.1 ± 3.5%, and trial 4: 7.0 ± 2.8%; HGEX trial 1: 7.3 ± 3.6%, trial 2: 7.0 ± 3.6%, trial 3: 6.5 ± 3.5%, and trial 4: 6.8 ± 2.9%, P = 0.913). No relationship between subject's RH %FMD and HGEX %FMD was detected (r(2) = 0.12, P = 0.137). However, with response normalization, a relationship emerged (RH %FMD/SR AUC vs. HGEX %FMD/mean SR, r(2) = 0.44, P = 0.002). In conclusion, with repeat trials, there were no systematic changes in RH or HGEX %FMD. The relationship between normalized RH and HGEX %FMD suggests that endothelial responses to different SS profiles provide related information regarding endothelial function.

Are the dynamic response characteristics of brachial artery flow-mediated dilation sensitive to the magnitude of increase in shear stimulus?

The purpose of this study was to determine the dynamic characteristics of brachial artery dilation in response to step increases in shear stress [flow-mediated dilation (FMD)]. Brachial artery diameter (BAD) and mean blood velocity (MBV) (Doppler ultrasound) were obtained in 15 healthy subjects. Step increases in MBV at two shear stimulus magnitudes were investigated: large (L; maximal MBV attainable), and small (S; MBV at 50% of the large step). Increase in shear rate (estimate of shear stress: MBV/BAD) was 76.8 +/- 15.6 s(-1) for L and 41.4 +/- 8.7 s(-1) for S. The peak %FMD was 14.5 +/- 3.8% for L and 5.7 +/- 2.1% for S (P < 0.001). Both the L (all subjects) and the S step trials (12 of 15 subjects) elicited a biphasic diameter response with a fast initial phase (phase I) followed by a slower final phase. Relative contribution of phase I to total FMD when two phases occurred was not sensitive to shear rate magnitude (r(2) = 0.003, slope P = 0.775). Parameters quantifying the dynamics of the FMD response [time delay (TD), time constant (tau)] were also not sensitive to shear rate magnitude for both phases (phase I: TD r(2) = 0.03, slope P = 0.376, tau r(2) = 0.04, slope P = 0.261; final phase: TD r(2) = 0.07, slope P = 0.169, tau r(2) = 0.07, slope P = 0.996). These data support the existence of two distinct mechanisms, or sets of mechanisms, in the human conduit artery FMD response that are proportionally sensitive to shear stimulus magnitude and whose dynamic response is not sensitive to shear stimulus magnitude.

Brachial artery flow-mediated dilation during handgrip exercise: evidence for endothelial transduction of the mean shear stimulus.

Exercise elevates shear stress in the supplying conduit artery. Although this is the most relevant physiological stimulus for flow-mediated dilation (FMD), the fluctuating pattern of shear that occurs may influence the shear stress-FMD stimulus response relationship. This study tested the hypothesis that the brachial artery FMD response to a step increase in shear is influenced by the fluctuating characteristics of the stimulus, as evoked by forearm exercise. In 16 healthy subjects, we examined FMD responses to step increases in shear rate in three conditions: stable shear upstream of heat-induced forearm vasodilation (FHStable); fluctuating shear upstream of heat-induced forearm vasodilation and rhythmic forearm cuff inflation/deflation (FHFluctuating); and fluctuating shear upstream of exercise-induced forearm vasodilation (FEStep Increase). The mean increase in shear rate (+/-SD) was the same in all trials (FHFluctuating): 51.69 +/- 15.70 s(-1); FHStable: 52.16 +/- 14.10 s(-1); FEStep Increase: 50.14 +/- 13.03 s(-1) P = 0.131). However, the FHFluctuating and FEStep Increase trials resulted in a fluctuating shear stress stimulus with rhythmic high and low shear periods that were 96.18 +/- 24.54 and 11.80 +/- 7.30 s(-1), respectively. The initial phase of FMD (phase I) was followed by a second, delayed-onset FMD and was not different between conditions (phase I: FHFluctuating: 5.63 +/- 2.15%; FHStable: 5.33 +/- 1.85%; FEStep Increase: 5.30 +/- 2.03%; end-trial: FHFluctuating: 7.76 +/- 3.40%; FHStable: 7.00 +/- 3.03%; FEStep Increase: 6.68 +/- 3.04%; P = 0.196). Phase I speed also did not differ (P = 0.685). In conclusion, the endothelium transduced the mean shear when exposed to shear fluctuations created by a typical handgrip protocol. Muscle activation did not alter the FMD response. Forearm exercise may provide a viable technique to investigate brachial artery FMD in humans.

Immediate exercise hyperemia in humans is contraction intensity dependent: evidence for rapid vasodilation.

We tested the hypothesis that rapid vasodilation proportional to contraction intensity contributes to the immediate (first cardiac cycle after initial contraction) exercise hyperemia. Ten healthy subjects performed single 1-s isometric forearm contractions at 5, 10, 15, 20, 30, 50, and 70% maximal voluntary contraction intensity (MVC) in arm above heart (AH) and below heart (BH) positions. Forearm blood flow (FBF; brachial artery mean blood velocity, Doppler ultrasound), mean arterial pressure (arterial tonometry), and heart rate (electrocardiogram) were measured beat by beat. Venous emptying (measured with a forearm strain gauge) was already maximized at 5% MVC, indicating that increases in contraction intensity did not further empty the forearm veins. Immediate increases in FBF were linearly proportional to contraction intensity from 5 to 70% MVC in AH (slope = 4.4 +/- 0.5%DeltaFBF/%MVC). In BH, the immediate increase in FBF demonstrated a curvilinear relationship with increasing contraction intensity and was greater than AH at 15, 20, 30, and 50% MVC (P < 0.05). Peak changes in FBF were greater in BH vs. AH from 10 to 50% MVC, even when venous refilling was complete (P < 0.05). These data support the existence of a rapid-acting vasodilatory mechanism(s) at the onset of human forearm exercise.