Brachial Artery Shear Research Articles

Similar endothelium-dependent vascular responses to intermittent hypoxia in young and older adults.

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults.NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Impact of moderate-intensity aerobic exercise in combined hypoxic and hot conditions on endothelial function.

There is no study that has investigated the impact of exercise in a combined hypoxic and hot environment on endothelial function. Therefore, we tested whether aerobic exercise in a combined hypoxic and hot conditions induces further enhancement of endothelial function. Twelve healthy males cycled at a constant workload (50% of their maximal oxygen uptake under normoxic/thermoneutral conditions) for 30 min in four different environments: exercise under normoxic condition (NOR: fraction of inspiratory oxygen or FiO2 = 20.9%, 20°C), exercise under hypoxic condition (HYP: FiO2 = 14.5%, 20°C), exercise under hot condition (HOT: FiO2 = 20.9%, 30°C), and exercise under combined hypoxia and hot conditions (HH: FiO2 = 14.5%, 30°C). Before, during, and after exercise, cardiovascular variables (e.g., heart rate, blood flow, and shear rate), blood variables, and endothelial function evaluated by flow-mediated dilation (FMD) were assessed. Heart rates were significantly higher throughout the HH trial's experimental period than the other trials (p < 0.05). However, in the HH trial, brachial artery blood flow and shear rate did not differ from those in other trials after exercise. Plasma catecholamines (epinephrine, norepinephrine, and dopamine) elevations in response to exercise were significantly higher in the HH trial than in the other three trials (p < 0.05). No considerable differences were observed in FMD responses among trials before and after the exercise. In conclusion, aerobic exercise in a combined hot and hypoxic environment further activated sympathetic nervous activity but did not considerably enhance blood flow, shear rate, or endothelial function.

Vascular responses during handgrip exercise in healthy postmenopausal females and older males

Introduction: Aerobic exercise interventions improve peripheral endothelial function in healthy older males. However, this effect is not always observed in healthy postmenopausal females and possible mechanisms underlying this sex-related difference remain unknown. Greater vascular shear stress during acute exercise is a key stimulus mediating longer-term improvements in vascular function. It remains unknown if postmenopausal females display a reduced endothelial sensitivity to exercise-induced shear stress relative to males of similar age. Objective and hypothesis: The objective of this study is to test the hypothesis that healthy postmenopausal females exhibit a lower endothelial sensitivity to exercise-induced shear stress relative to males. Methods: Fourteen healthy postmenopausal females (67 ± 8 years) not under hormone replacement therapy and 9 males of similar age (65 ± 7 years) performed handgrip exercise for 4 minutes at 20%, 40%, 60%, and 80% of their maximal voluntary contraction. Each exercise bout was separated by a 10-min recovery period. Brachial artery diameter and blood velocity were continuously measured using high-resolution ultrasound and analyzed using edge-detection software. Endothelial sensitivity to shear rate was quantified as the slope of the linear regression between brachial artery dilation (% change from baseline) and shear stress and compared between groups with an independent t-test. Workload, vascular conductance, diameter dilation, and shear stress were analyzed with mixed-effects models. Results: Males exercised at greater workloads relative to females across all exercise bouts (M: 17 ± 11 vs. F: 9 ± 5 kg, p&lt;0.01). Forearm vascular conductance was greater in males throughout each exercise intensity (M: 2.23 ± 1.70 vs. F: 1.03 ± 0.51 ml/min/mmHg, p=0.02). Despite these differences, arterial dilation (M: 5.32 ± 5.55 vs. F: 5.20 ± 4.80%, p=0.96) and shear stress (M: 142 ± 80 vs. F: 171 ± 86 s−1, p=0.27) did not differ between groups across exercise intensities. Endothelial sensitivity to exercise-induced shear stress did not differ between males (0.02 ± 0.05%/s−1) and females (0.03 ± 0.01%/s−1, p=0.67). Conclusion: These data suggest that a reduced endothelial sensitivity to exercise-induced shear stress may not explain why aerobic exercise interventions do not consistently improve peripheral endothelial function in healthy postmenopausal females. Montreal Heart Institute Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone.

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak . Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone.

Acute inspiratory resistance training enhances endothelium-dependent dilation and retrograde shear rate in healthy young adults.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously.

Brachial Artery Shear Rate Responses To Sprint Efforts And Moderate Intensity Cycling

Brachial Artery Shear Rate Responses To Sprint Efforts And Moderate Intensity Cycling

Brachial artery flow-mediated dilation during incremental handgrip exercise is not impacted by sex or female sex hormones

Sex differences exist in reactive hyperemia flow-mediated dilation (RH-FMD), with males demonstrating larger RH-FMD responses than naturally menstruating females and females using oral contraception (OC). This difference is thought to be partly attributed to sex hormones. Among females, some studies demonstrate lower RH-FMD in females using OC relative to naturally menstruating females. To date, non-invasive assessments of endothelial function in males, naturally cycling females and females using OC have only been completed using RH-FMD. Notably, due to differences in the shear stimulus during sustained shear-induced FMD (SS-FMD) versus the transient pattern observed with RH-FMD, SS-FMD may provide distinct insight into endothelial dysfunction undetected with RH-FMD. Therefore, we hypothesized that the SS-FMD responses to incremental handgrip (IHG) exercise would be greatest in males, and that females using OC would have the smallest increase in SS-FMD compared to males and naturally menstruating females. The IHG protocol consisted of 3-minute stages of rhythmic handgrip exercise at 15, 30, and 45% of an individual’s maximal voluntary contraction (MVC) force, with no rest period between MVC transitions. Brachial artery diameter and blood velocity were measured simultaneously via duplex Doppler ultrasound in 10 males (26±4 [mean±SD] years), 11 naturally menstruating females (25±4 years), and 9 females using OC (27±5 years) during IHG. Females were tested in the mid-luteal (ML) and active (high hormone) OC phases. SS-FMD and shear rate were analyzed using linear mixed model analyses. MVC was greater in males relative to both groups of females (males: 40±6, ML: 28±8, OC: 26±6 kg; One-way ANOVA: post-hocs P≤0.001). Brachial artery shear rate was not different between males, ML females or females using OC throughout exercise (group-by-stage interaction: P=0.975). Consequently, the brachial artery dilated by 1.3±1.5, 0.1±2.1, and 1.2±3.6 % at 15% MVC, 4.0±3.1, 2.7±3.3, and 4.1±4.8 % at 30% MVC, and 9.1±4.9, 7.3±5.4, and 7.6±5.9 % at 45% MVC, in males, ML females, and females using OC, respectively (all P&gt;0.05). Furthermore, the slopes of the relationship between the change in brachial artery diameter and shear rate was similar between the three groups (Males: 0.0004±0.0002, ML: 0.0003±0.0002, OC: 0.0003±0.0002 Δmm/Δ1·s -1 ; One-way ANOVA: P=0.564). Taken together, these data indicate that endothelial function in response to sustained elevations in shear stress are not impacted by biological sex or OC use. Supported by the Natural Sciences and Engineering Research Council of Canada, and IEEM indirect funds. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The impact of age on the vascular response to acute sauna exposure

Passive heat exposure has been shown to be a promising method to improve endothelial health. Sauna usage specifically, has been linked to reduced risk of cardiovascular disease in young and middle-aged populations. Increases in blood flow and shear rates associated with heat exposure are often considered to have a major influence on the observed improved endothelial function following repeated heat exposure; however, the magnitude of these shear and flow responses may potentially vary with age or starting endothelial function. Purpose: The purpose of this study was to determine if the vascular response to acute sauna heating is similar between healthy young and middle-aged adults and if the response is related to baseline endothelial function. Methods: 10 young (24.9 ± 4.2 years, 6 male and 4 female) and 8 middle aged adults (55.6 ± 3.9 years 4 males and 4 females) underwent 40 min of sauna exposure at 80ºC. Esophageal temperature was recorded throughout the duration of the experiment. Brachial artery flow-mediated dilation (FMD) blood flow, artery diameter, shear rates and blood pressure were recorded at baseline and following heat exposure. Results: The increase in core temperature (Tc) followed similar trends in both the young and middle-aged adults (young ΔTc = 1.386 ± 0.52 ºC vs middle-Age Δ Tc = 1.637 ± 0.56 ºC). Heat-induced brachial artery dilation and brachial artery shear rate also increased similarly in both age groups (young Δ diameter = 0.048 ± 0.022 cm vs middle-age Δ diameter = 0.074 ± 0.036 cm, young Δ shear = 164.5± 106.8 sec- 1 vs middle-age Δ shear = 150.3 ± 56.29 sec -1 ). Heat induced dilation was strongly correlated to baseline endothelial function in the young (r = 0.86, P=0.006). This relationship was not observed in the brachial artery of middle-aged adults (r = 0.257, P=0.539). Systolic blood pressure (SBP) was significantly reduced following sauna in the middle-aged participants from 135.25 ± 17.50 mmHg to 122.38 ± 19.7 mmHg (P=0.017). There was a slight elevation in SBP following sauna in the young participants from 119.4 ± 6.38 mmHg to 123.1 ± 7.65 mmHg (P=0.017). Diastolic blood pressure (DBP) was significantly reduced in both age groups (P&lt;0.001) with middle age seeing greater reductions (P=0.05) from 80.63 ± 10.97 mmHg to 69.75 ± 8.41 mmHg vs the young 71.2 ± 8.24 mmHg to 66.9 ± 4.56 mmHg. Conclusion: Young and middle-aged adults have similar changes in shear rate and brachial artery dilation in response to acute sauna heating, but the middle-aged adults exhibit significantly greater decreases in SBP and DBP than young adults. In young adults, endothelial function is strongly correlated to heat induced dilation in the brachial artery. This relationship is not present in the middle age population suggesting that heat-induced dilation may rely on mechanisms other than endothelial function in middle-aged adults. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of exercise during water immersion on arterial function in humans.

Flow-mediated dilation (FMD) provides a valid bioassay of vascular function in humans. Although water immersion induces hemodynamic effects that modify brachial artery shear stress, it is unclear whether water-based exercise modifies FMD. We hypothesized that exercise in 32°C water would decrease brachial artery shear and FMD relative to land-based exercise, whereas exercise in 38°C would increase brachial shear and FMD. Ten healthy participants (8 males; 23.9 ± 3.3 yr) completed 30 min of resistance-matched cycle exercise in three separate conditions: on land and in 32°C and 38°C water. Brachial artery shear rate area under the curve (SRAUC) was measured throughout each condition, with FMD measured pre- and postexercise. Brachial SRAUC increased during exercise in all conditions and was highest across the 38°C condition compared with Land and 32°C conditions (38°C: 27,507 ± 8,350 vs. Land: 9,908 ± 4,738 vs. 32°C: 13,840 ± 5,861 1/s, P < 0.001). Retrograde diastolic shear was greater during 32°C than both Land and 38°C conditions (32°C:-3,869 ± 2,198 vs. Land:-1,602 ± 1,334 vs. 32°C:-1,036 ± 1,754, P < 0.01). FMD increased as a result of 38°C (6.2 ± 1.9 vs. 8.5 ± 2.7%, P = 0.03), with no change in the Land exercise (6.3 ± 2.4 vs. 7.7 ± 2.4%, P = 0.10) or 32°C condition (6.4 ± 3.2 vs. 6.7 ± 3.2%, P = 0.99). Our findings indicate that cycle exercise in hot water attenuates retrograde shear, increases antegrade shear, and FMD. Exercise in 32°C water induces central hemodynamic changes relative to land-based exercise, but these do not translate to increases in FMD in either condition, likely due to the impact of increased retrograde shear. Our findings indicate that modification of shear has direct acute impacts on endothelial function in humans.

Hypoxia offsets the decline in brachial artery flow-mediated dilation after acute inactivity.

Intermittent (IH), as opposed to continuous hypoxia (CH), is thought to have beneficial effects on cardiovascular function and health. In the present study, we examined the acute effects of IH and CH (∼80% pulse oxygen saturation via 10% oxygen tank) on peripheral vascular function. Brachial artery flow-mediated dilation (FMD) was used to assess vascular function in 12 young adults (23 ± 5 yr; 8 M/4 F) before and after 50 min of IH (5 cycles; 4-min normoxia/6-min hypoxia per cycle), CH (20-min normoxia followed by 30-min hypoxia), or time control (50-min normoxia) interventions. Brachial artery diameter and velocity were measured using Doppler ultrasound to assess blood flow and shear rate. The total change in shear rate was greater during IH (634 ± 1,073·s-1, P < 0.05) and CH (321 ± 833·s-1, P = 0.05) than during time control (-412 ± 789·s-1). %FMD was reduced following time control (7.4 ± 1.2 to 5.9 ± 1.1%, P < 0.05) but was maintained following both hypoxia trials (IH: 7.2 ± 1.5 to 7.5 ± 1.5%, P = 0.52; CH: 6.9 ± 1.6 to 6.8 ± 1.4%, P = 0.73). Normalized %FMD for shear rate area under the curve (%FMDSRAUC) was reduced following the time control trial (4.2 ± 1.4 to 3.7 ± 0.9%, P < 0.05) with no change observed with CH (4.0 ± 1.5 to 3.9 ± 1.4%, P = 0.71). However, %FMDSRAUC increased with IH (3.8 ± 1.1 to 4.5 ± 1.5%, P < 0.05). Our data suggest that acute exposure to hypoxia (both intermittently and continuously) offsets the decline in vascular function after brief inactivity. The potential beneficial effect of hypoxia on peripheral vascular function observed in the current study may be associated with enhanced brachial artery shear in response to the hypoxic challenge.

Endothelial Sensitivity to Exercise‐Induced Shear Rate in Pre‐ and Post‐Menopausal Females and in Males

BACKGROUNDPost‐menopausal females appear resistant to the beneficial effects of exercise on endothelial function. Repeated increases in shear stress are considered important mediators of exercise‐induced improvements in endothelial function. It is therefore possible that endothelial sensitivity to shear stress is reduced in post‐menopausal females, thereby blunting endothelial adaptations to exercise training. The objective of this retrospective analysis was to test the hypothesis that post‐menopausal females exhibit a lower endothelial sensitivity to exercise‐induced shear rate relative to pre‐menopausal females and age‐matched males.METHODSFive pre‐ (48 ± 1 yrs) and fifteen post‐ (65 ± 10 yrs) menopausal females, and five males (67 ± 5 yrs) performed 4‐min rhythmic handgrip exercise bouts. Ten participants (6 post and 6 males) exercised at 20%, 40%, 60% and 80% of maximal voluntary contraction, and 15 participants (5 pre, 9 post and 2 males) exercised at 3 kg, 6 kg and 9 kg. The contraction/relaxation cycle was 2‐sec/3‐sec and each bout was separated by 10 min of rest. Brachial artery diameter and blood velocity were measured using high‐resolution ultrasound and analyzed using edge‐detection software. Endothelial sensitivity to exercise‐induced shear rate was quantified as the slope of the relationship between brachial artery dilation (% change from baseline) and shear rate (in s‐1).RESULTSBaseline diameter was greater in males (4.68 ± 0.55 mm) compared with post‐ (3.24 ± 0.53 mm, p&lt;0.01) and pre‐ (3.55 ± 0.19 mm, p&lt;0.01) menopausal females. The rhythmic handgrip protocols elicited net shear rates that ranged between 38 s‐1 and 392 s‐1. A positive correlation was observed between brachial artery dilation and net shear rate in males (r=0.66, p&lt;0.01), and post‐menopausal females (r=0.38; p&lt;0.01), but not in pre‐menopausal females (r=‐0.25, p=0.36). Endothelial sensitivity to exercise‐induced shear rate did not differ between pre‐ (0.037 ± 0.120 %/s‐1)and post‐ (0.069 ± 0.081 %/s‐1, p&gt;0.99) menopausal females, between pre‐menopausal females (0.037 ± 0.120 %/s‐1)and males (0.027 ± 0.055 %/s‐1, p&gt;0.99), or between post‐menopausal females (0.069 ± 0.081 %/s‐1) and males (0.027 ± 0.055 %/s‐1, p&gt;0.99).CONCLUSIONThese results suggest that post‐menopausal females do not demonstrate a reduced endothelial sensitivity to exercise‐induced shear rate compared with pre‐menopausal females as well as with males of similar age.

Comparing the Effects of 30‐ and 60‐min of Acute Whole‐Body Passive Heat Stress on Peripheral Vascular Function in Older Adults

IntroductionMacro‐ and microvascular dysfunction elevate the risk of cardiovascular disease (CVD). Heat therapy has the potential to improve vascular health and reduce CVD risk, but the optimal length of heat stress exposure is unknown. We hypothesized that 1) acute whole body heat stress (WBHS) would increase vascular function and 2) a longer WBHS period (30‐ vs 60‐min) would elicit a greater effect.Methods20 older adults (10 female; 64±7 y) underwent two separate periods of WBHS (30‐ vs 60‐min) via water perfused suit (48°C) in a randomized, counterbalanced design. Macrovascular function via flow‐mediated dilation (FMD) and microvascular function via skin reactive hyperemia (SKBF RH) were assessed before (PRE) and after (POST) WBHS. Core (Tcore; rectal) and skin (Tskin; 6‐site average) temperatures were monitored throughout. Repeated measures ANOVA were used to assess the effect of time (PRE vs POST) and visit (30‐ vs 60‐min) on all outcomes.ResultsTcore and Tskin increased after both WBHS periods (Tcore: 30‐min, PRE: 36.4±0.3, POST: 36.6±0.3°C; 60‐min, PRE: 36.4±0.3, POST: 36.8±0.2°C, p=0.001; Tskin: 30‐min, PRE: 33.5±0.6, POST: 36.3±0.4°C, p&lt;0.0005; 60‐min, PRE: 33.2±0.5°C, POST: 36.6±0.5°C, p&lt;0.0005). FMD% was unchanged (30‐min, PRE: 8.5±5.1%, POST: 7.1±4.2%; 60‐min, PRE: 7.7±3.9%, POST: 6.6±4.3%; p=0.10) after both WBHS periods. During RH, brachial artery shear rate area under the curve was higher after 30‐ (PRE: 17.08±9.57, POST: 26.34±13.06·10‐3 AUC; p=0.003) but not 60‐min (PRE: 21.06±12.30, POST: 27.83±19.32·10‐3 AUC; p=0.186). Total SKBFAUC increased following both 30‐ (PRE: 6.31±3.22, POST: 12.82±6.44·10‐3 AUC; p&lt;0.0005) and 60‐min (PRE: 6.01±3.24, POST: 9.609±4.882·10‐3 AUC; p=0.037), whereas peak SKBF fluxAUC increased following 30‐ (PRE: 1.86±1.54, POST: 4.15±3.07·10‐3 AUC; p=0.001) but not 60‐min (PRE: 1.58±1.31, POST: 2.93±2.77·10‐3 AUC; p=0.1113) of WBHS.DiscussionUp to 60‐min of acute WBHS does not change macrovascular function in older adults. Interestingly, WBHS might increase downstream microvascular functional capacity. The changes in microvascular function following 30‐min of WBHS may reflect early markers of the benefits of repeated whole body heat stress.

Prenatal exercise and cardiovascular health (PEACH) study: the remote effect of aerobic exercise training on conduit artery and resistance vessel function.

We assessed the impact of a structured lower-limb aerobic exercise training intervention during pregnancy on brachial artery endothelial function, shear rate and patterns, and forearm blood flow and reactive hyperemia. Twenty-seven pregnant women were recruited and randomized into either a control group (n= 11; 31.0± 0.7 years), or an exercise intervention group (n= 16; 32.6± 0.9 years). The exercise group completed 40minutes of aerobic exercise (50-70% heart rate reserve) 3-4 times per week, between the second and third trimester of pregnancy. Endothelial function was assessed using flow-mediated dilation (FMD, normalized for shear stress) at pre- (16-20 weeks) and post-intervention (34-36 weeks). The exercise training group experienced an attenuated increase in mean arterial pressure (MAP) relative to the control group (ΔMAP exercise: +2± 2mm Hg vs. control: +7± 3mm Hg; p= 0.044) from pre- to post-intervention. % FMD change corrected for shear stress was not different between groups (p= 0.460); however, the post-occlusion mean flow rate (exercise: 437± 32mL/min vs. control: 364± 35mL/min; p= 0.001) and post-occlusion anterograde flow rate (exercise: 438± 32mL/min vs. control: 364± 46mL/min; p= 0.001) were larger for the exercise training group compared with controls, post-intervention. Although endothelial function was not different between groups, we observed an increase in microcirculatory dilatory capacity, as suggested by the augmented reactive hyperemia in the exercise training group. Registered at ClinicalTrials.gov: NCT02948439. Novelty: Endothelial function was not altered with exercise training during pregnancy. Exercise training did contribute to improved cardiovascular outcomes, which may have been associated with augmented reactive hyperemia, indicative of increased microcirculatory dilatory capacity.

Effects of cooling or warming of the distal upper limb on skin vascular conductance and brachial artery shear profiles during cycling exercise

ABSTRACT The relative influence of skin vascular conductance in glabrous (G; palm) and non-glabrous (NG; dorsal and forearm) regions to upstream brachial artery-shear stress (BA-SS) profile are unknown. This study aimed to elucidate the effects of G and/or NG skin vascular conductance (VC), which were modulated by warming or cooling manipulation, on BA-shear rate (SR, an estimate of SS) during cycling exercise. Seven healthy subjects performed 60-min exercise. Between 20 and 50 min of the exercise, the NG+G or G skin region were warmed to 42°C or cooled to 15°C using a water bath. Throughout the protocol, diameter and blood velocity in BA and skin VCs in forearm and palm were measured. All measurements showed that a steady-state response was reached after 20 min of exercise. Subsequently, during cooling manipulation, forearm VC was significantly decreased, and the concomitant BA-SR profile was revealed (primarily characterized by decreased antegrade SR and increased retrograde SR) in the NG+G. Such changes were not observed in G alone. During warming manipulation, forearm VC and mean BA-SR significantly increased only in the NG+G. In conclusion, vascular response in NG skin possibly plays a major role in the modulation of BA-SS profile during cycling exercise.

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

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

Effects of Unilateral Arm Warming or Cooling on the Modulation of Brachial Artery Shear Stress and Endothelial Function during Leg Exercise in Humans.

Aim: We examined the effect of modulating the shear stress (SS) profile using forearm warming and cooling on subsequent endothelial function in the brachial artery (BA) during exercise.Methods: Twelve healthy young subjects immersed their right forearm in water (15°C or 42°C) during a leg cycling exercise at 120–130 bpm for 60 min. The same exercise without water immersion served as a control. The BA diameter and blood velocity were simultaneously recorded using Doppler ultrasonography to evaluate the antegrade, retrograde, and mean shear rates (SRs, an estimate of SS) before, during, and after exercise. The endothelial function in the right BA was evaluated using flow-mediated dilation (FMD) (%) using two-dimensional high-resolution ultrasonography before (baseline) and 15 and 60 min after exercise.Results: During exercise, compared with the control trial, higher antegrade and mean SRs and lower retrograde SRs were observed in the warm trial; conversely, lower antegrade and mean SRs and higher retrograde SRs were observed in the cool trial. At 15 min postexercise, no significant change was observed in the FMD from baseline in the warm (Δ%FMD: +1.6%, tendency to increase; p = 0.08) and control trials (Δ %FMD: +1.1%). However, in the cool trial, the postexercise FMD at 60 min decreased from baseline (Δ%FMD: −2.7%) and was lower than that of the warm (Δ%FMD: +1.5%) and control (Δ%FMD: +1.2%) trials. Accumulated changes in each SR during and after exercise were significantly correlated with postexercise FMD changes.Conclusion: Modulation of shear profiles in the BA during exercise appears to be associated with subsequent endothelial function.

Acute blood glucose and vascular endothelial responses to passive heating in individuals with type 2 diabetes

IntroductionInsulin resistance and hyperglycemia predispose individuals with type 2 diabetes mellitus (T2DM) to endothelial dysfunction and a greater risk of cardiovascular diseases. Numerous animal studies suggest that heat exposure improves glucose control and human studies suggest that it improves markers of vascular health. However, the physiological responses to heat exposure remain understudied in individuals with T2DM, particularly within a therapeutic context.ObjectiveTo characterize blood glucose and vascular endothelial responses to heat exposure in T2DM and determine if heating acutely improves glucose control and endothelial function in this population.MethodsOn separate randomized days, six adults (2 males/4 females, 60 ± 12 years) with T2DM (≥1 year, HbA1c: 7.0 ± 0.5%, fasting glucose: 7.79 ± 1.13 mmol/L) were immersed in control (34°C, 90 minutes) or hot (40–41°C, core temperature ≥38.5°C for 60 minutes) water. Participants were fasted (12 hours) and withheld anti‐diabetic medication (≥24 hours). Blood glucose and insulin as well as brachial artery shear rates were measured at baseline, during immersion and 45–60 minutes after immersion. Brachial artery flow‐mediated dilation (FMD) was measured at baseline and 45 minutes after immersion. Blood glucose control was evaluated during an oral glucose tolerance test (OGTT, 75 g) 60 minutes after immersion. Core (Tcore, rectal) and mean skin (Tskin) temperatures, heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures were measured throughout the protocol.ResultsCompared to control, hot water immersion increased Tcore (+1.44°C [1.05, 1.83], P&lt;0.01), Tskin (+2.36°C [1.21, 3.51], P&lt;0.01), HR (+35 bpm [26, 43], P&lt;0.01), and decreased DBP (−7 mmHg [−2, −13], P&lt;0.01) and SBP (−9 mmHg [−1, −16], P=0.03). Hot water immersion increased antegrade (+71 s−1 [35, 107], P&lt;0.01) and decreased retrograde (−15 s−1 [0.9, 3], P=0.06) shear rates. Nonetheless, FMD was unchanged during both control (−0.74% [−4.33, 2.86], P=0.81) and hot (−1.93% [−5.53, 1.66], P=0.30) water immersion. Blood glucose decreased progressively throughout the control protocol (−1.3 mmol/L [−0.8, −1.9], P&lt;0.01), whereas hot water immersion attenuated this decrease (+0.1 mmol/L [−0.5, +0.6], P=0.93). Hot water immersion did not alter glucose (P=0.17) and insulin (P=0.99) area under the curve during the OGTT.ConclusionThese preliminary results suggest that the physiological responses associated with heat exposure do not translate into acute improvements in blood glucose control or brachial artery endothelial function in individuals with T2DM.Support or Funding InformationCardiometabolic Health, Diabetes and Obesity Research Network and Diabetes Quebec.

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

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

Global REACH 2018: High Blood Viscosity and Hemoglobin Concentration Contribute to Reduced Flow-Mediated Dilation in High-Altitude Excessive Erythrocytosis

Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk in highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) in male Andeans with and without EE. We hypothesized that FMD would be impaired in Andeans with EE after accounting for shear stress and that FMD would improve after isovolemic hemodilution. Brachial artery shear stress and FMD were assessed in 23 male Andeans without EE (age: 40±15 years [mean±SD]; Hb<21 g/dL) and 19 male Andeans with EE (age: 43±14 years; Hb≥21 g/dL) in Cerro de Pasco, Peru (4330 m). Shear stress was quantified from Duplex ultrasound measures of shear rate and blood viscosity. In a subset of participants (n=8), FMD was performed before and after isovolemic hemodilution with blood volume replaced by an equal volume of human serum albumin. Blood viscosity and Hb were 48% and 23% higher (both P<0.001) and FMD was 28% lower after adjusting for the shear stress stimulus ( P=0.013) in Andeans with EE compared to those without. FMD was inversely correlated with blood viscosity ( r2=0.303; P<0.001) and Hb ( r2=0.230; P=0.001). Isovolemic hemodilution decreased blood viscosity by 30±10% and Hb by 14±5% (both P<0.001) and improved shear stress stimulus-adjusted FMD from 2.7±1.9% to 4.3±1.9% ( P=0.022). Hyperviscosity, high Hb, or both, actively contribute to acutely reversible impairments in FMD in EE, suggesting that this plays a pathogenic role in the increased cardiovascular risk.

Peripheral artery endothelial function responses to altered shear stress patterns in humans.

What is the central question of this study? What is the effect of altered shear stress pattern, with or without concurrent neurohumoral and metabolic activation, on the acute endothelial function response assessed via brachial artery flow-mediated dilatation? What is the main finding and its importance? Despite generating distinctive shear stress patterns (i.e. increases in anterograde only, anterograde only with neurohumoral and metabolic activation, and both anterograde and retrograde), similar acute improvements were observed in the brachial artery flow-mediated dilatation response in all conditions, indicating that anterograde and/or turbulent shear stress might be the essential element to induce acute increases in endothelial function. Endothelial function is influenced by both the direction and the magnitude of shear stress. Acute improvements in endothelial function have mostly been attributed to increased anterograde shear, whereas results from many interventional models in humans suggest that enhancing shear stress in an oscillatory manner (anterograde and retrograde) might be optimal. Here, we determined the acute brachial artery shear stress (SS) and flow-mediated dilatation (FMD) responses to three shear-altering interventions [passive heat stress (HEAT), mechanical forearm compression (CUFF) and handgrip exercise (HGEX)] and examined the relationship between changes in oscillatory shear index (OSI) and changes in FMD. During separate visits, 10 young healthy men (22±3years old) underwent 10min of HEAT, CUFF or HGEX in their left forearm. Anterograde and retrograde SS, Reynolds number, OSI and FMD were assessed at rest and during/after each intervention. Anterograde SS increased during all interventions in a stepwise manner (P<0.05 between interventions), with the change in HGEX (∆37.7±12.2dyncm-2 , P<0.05)>CUFF (∆25.1±11.9dyncm-2 , P<0.05)>HEAT (∆14.5±7.9dyncm-2 , P<0.05). Retrograde SS increased during CUFF (∆-19.6±4.3dyncm-2 , P<0.05). Anterograde blood flow was turbulent (i.e. Reynolds number≥|2000|) during all interventions (P<0.05). The relative FMD improved after all interventions (P=0.01), and there was no relationship between ∆OSI and ∆FMD. We elicited changes in SS profiles including increased anterograde SS (HEAT and HGEX) and both increased anterograde and retrograde SS (CUFF); regardless of the SS pattern, FMD improved to the same extent. These findings suggest that the presence of anterograde and/or turbulent SS might be the key to optimizing endothelial function in acute assessment protocols.