Popliteal Flow-mediated Dilation Research Articles

The effects of prolonged sitting with a mild hypercapnic environment on vascular function in elderly adults: A pilot study

Introduction: Prolonged Sitting (PS), defined a sitting for 2+ hours at a time, has been identified as an independent risk factor for cardiovascular disease (CVD). We previously reported that an acute bout of PS can attenuate macrovascular function in healthy young adults. Additionally, we reported that PS in mild hypercapnic environments (elevated CO2 concentrations) can further exacerbate these impairments in healthy young adults, and these impairments can be partially prevented by intermittent bouts of passive and active leg movements. However, the effects of prolonged sitting with a mild hypercapnic environment in the elderly population have not been studied. Therefore, the purpose of this study was to examine the impact of prolonged sitting with a mild hypercapnic condition on macrovascular function, arterial stiffness, and leg muscle metabolism. Additionally, we have further examined the effects of passive and active movements to negate the negative effects of prolonged sitting in elderly adults. Hypothesis: We hypothesized that 1) prolonged sitting in a hypercapnic environment will attenuate vascular function and leg metabolism, 2) both passive and active leg movements will preserve endothelial function and leg metabolism. Methods: Healthy elderly adults (n=2, 2 males, 69 ± 2.83 yrs) participated in three experimental visits consisting of 2.5h of prolonged sitting in a mild hypercapnic condition (CO2 = 1500ppm): control (CON), passive (PASS, passive leg movement), and active (ACT, active leg movement). Popliteal and brachial artery endothelial function was measured using flow-mediated dilation (FMD). Peripheral and central arterial stiffness was assessed using pulse wave velocity. Leg muscle metabolism was assessed using near infrared spectroscopy and a thermal camera. All measurements were taken pre- and post-siting. Results: Popliteal FMD was reduced in the CON condition compared to both the PASS and ACT (Δ -3.559 ± 0.499 vs Δ -1.799 ± 0.824 vs Δ 0.601 ± 1.958, respectively). Brachial FMD was attenuated in the CON condition compared to both compared to both the PASS and ACT (Δ -2.368 ± 0.215 vs Δ -0.285 ± 1.578 vs Δ 1.116 ± 1.174, respectively). The CON condition showed a greater reduction in leg temperature compared to both the PASS and ACT (Δ -2.4 vs Δ -1.6 ± 0.599 vs Δ 0.1 ± 0.224, respectively). No changes in central or peripheral arterial stiffness were observed. Conclusion: This preliminary data shows that uninterrupted prolonged sitting induces impairments in both local and systemic vascular function, leg muscle metabolism, but not arterial stiffness. Additionally, intermittent bouts of passive and active movements can partially preserve leg vascular function and metabolism during PS. This research was supported by the UNO Graduate Research and Creative Activity Grant, National Institutes of Health (RO1HD106911) and the Great Plains IdeaA-CTR (U54 GM115448). 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.

A larger low-flow-mediated constrictor response is associated with augmented flow-mediated dilation in the popliteal artery.

In the brachial artery, conflicting evidence exists regarding the relationship between the low-flow-mediated constriction (L-FMC) and subsequent flow-mediated dilation (FMD) responses, which may confound interpretation of the latter. The popliteal artery is a common site for atherosclerotic development, which is preceded by endothelial dysfunction. We aimed to determine whether the magnitude of popliteal L-FMC impacted FMD responses, which is currently unknown. L-FMC and FMD were assessed in the popliteal artery via high-resolution duplex ultrasonography and quantified as the percent change in diameter (from baseline) during ischaemia and in response to hyperaemia, respectively. Using partial correlations and multiple regression analyses, we evaluated the association between popliteal L-FMC on FMD in 110healthy participants (60 females; 42±22 [19-77] years). All variables univariately associated (p<0.05) with popliteal relative FMD (relative L-FMC, log-SRAUC , age, systolic blood pressure, diastolic blood pressure, resting shear rate) were inputted into a model that explained 35% of the variance. The reactive hyperaemia stimulus (log-SRAUC : β=1.10) and relative L-FMC (β=-0.39) were the only independent predictors of FMD (both, p<0.01). Relative L-FMC was negatively correlated to relative FMD, after controlling for the significant univariate predictor variables listed above (R=-0.30; p=0.002). An augmented (ie healthier) L-FMC response was linked with a larger FMD response as determined by the independent inverse association observed between these shear-stress-mediated measures of vasoreactivity.

Does aerobic fitness impact prolonged sitting-induced popliteal artery endothelial dysfunction?

Acute prolonged bouts of sitting reduce popliteal artery blood flow and flow-mediated dilation (FMD). Individuals with higher aerobic fitness have enhanced popliteal FMD. Conflicting evidence regarding whether more aerobically fit individuals are protected from the negative impacts of sitting on popliteal endothelial function in male-dominated studies have been reported. We further explored the relationship between aerobic fitness and sitting-induced impairments in popliteal blood flow and FMD in a more sex-balanced cohort. Relative peak oxygen consumption (V̇O2peak) was assessed using a cycling-based incremental test in 21 healthy adults (eight males; 23 ± 2years; 23.9 ± 2.9kg/m2). Popliteal blood flow and relative FMD (%) were measured via duplex ultrasonography before and after 3 h of uninterrupted sitting. Pearson correlations were performed separately between V̇O2peak versus pre-sitting and sitting-induced reductions in popliteal outcomes. Aerobic fitness (41.0 ± 9.7ml/kg/min) was positively correlated with pre-sitting popliteal blood flow (65 ± 23mL/min; R = 0.59, P = 0.005) and relative FMD (4.2 ± 1.5%; R = 0.49, P = 0.03). As expected, sitting reduced resting blood flow (19 ± 11mL/min) and FMD (1.9 ± 0.7%) (both, P < 0.001). V̇O2peak was inversely related to sitting-induced declines in blood flow (Δ-46 ± 23mL/min; R = -0.71, P < 0.001) and FMD (Δ-2.4 ± 1.5%; R = -0.51, P = 0.02). Although higher aerobic fitness was associated with more favorable popliteal endothelial-dependent vasodilator responses, it also corresponded with larger sitting-induced impairments in FMD. This suggests that being more aerobically fit does not protect against sitting-induced vascular endothelial dysfunction. As such, all young adults should minimize habitual prolonged sedentary bouts, regardless of their aerobic fitness level.

The impact of age and sex on popliteal artery endothelial-dependent vasodilator and vasoconstrictor function.

Lower-limb arteries, such as the popliteal artery, are a common site of atherosclerosis. These arteries are habitually exposed to large fluctuations in blood flow during physical and sedentary activities. Low-flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) provide indices of endothelial-dependent vasoconstriction and vasodilation, respectively. Age and sex both impact upper-limb FMD. However, it is unclear whether these factors also influence popliteal endothelial-dependent function. Popliteal endothelial function was compared between younger and older males and females (n=14 per group) matched for age- and sex-specific relative aerobic fitness levels (each group's normative percentile: ~45%). Nitroglycerin-mediated dilation (NMD) was also assessed as a measure of endothelial-independent vasodilation. Ageing reduced relative popliteal FMD in both males (older: 4.3±1.8% versus younger 5.7±1.9%) and females (older: 2.9±1.8% versus younger: 6.1±1.6%, both: P<0.046). FMD was also lower in older females versus older males (P=0.04). Popliteal NMD findings followed the same pattern as FMD. Compared to younger adults, relative L-FMC responses were blunted among older males (older: -1.2±1.1% versus younger: -2.2±1.0%) and females (older: -1.0±1.2% versus younger: -2.1±1.3%, both P<0.03) with no sex-differences observed in either age group (all, P>0.60). The adverse age- and sex-related (older adults only) declines in popliteal FMD were mediated, in part, by reduced vascular smooth muscle sensitivity to nitric oxide. Endothelial-dependent vasoconstriction was also attenuated with age, but unaffected by sex. Despite similar normative aerobic fitness percentiles (~45%), older adults exhibited attenuated popliteal endothelial function than their younger counterparts. This was particularly evident in older females who exhibited the lowest endothelial-dependent vasodilatory responses.

Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease.

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function that, in turn, led to improved vascular function in older adults and animal models. However, the roles of vascular mitochondria in vascular function including endothelial function and arterial stiffness in patients with PAD are unknown; therefore, with the use of acute MitoQ intake, this study examined the roles of vascular mitochondria in endothelial function, arterial stiffness, exercise tolerance, and skeletal muscle function in patients with PAD. Eleven patients with PAD received either MitoQ or placebo in a randomized crossover design. At each visit, blood samples, brachial and popliteal artery flow-mediated dilation (FMD), peripheral and central pulse-wave velocity (PWV), blood pressure (BP), maximal walking capacity, time to claudication (COT), and oxygen utility capacity were measured pre- and-post-MitoQ and placebo. There were significant group by time interactions (P < 0.05) for brachial and popliteal FMD that both increased by Δ2.6 and Δ3.3%, respectively, and increases superoxide dismutase (Δ0.03 U/mL), maximal walking time (Δ73.8 s), maximal walking distance (Δ49.3 m), and COT (Δ44.2 s). There were no changes in resting heart rate, BP, malondialdehyde, total antioxidant capacity, PWV, or oxygen utility capacity (P > 0.05). MitoQ intake may be an effective strategy for targeting the vascular mitochondrial environment, which may be useful for restoring endothelial function, leg pain, and walking time in patients with PAD.NEW & NOTEWORTHY The results of this study reveal for the first time that acute oral intake of mitochondrial-targeted antioxidant (MitoQ, 80 mg) is effective for improving vascular endothelial function and superoxide dismutase in patients with peripheral artery disease (PAD). Acute MitoQ intake is also effective for improving maximal walking capacity and delaying the onset of claudication in patients with PAD. These findings suggest that the acute oral intake of MitoQ-mediated improvements in vascular mitochondria play a pivotal role for improving endothelial function, the redox environment, and skeletal muscle performance in PAD.

Sex does not influence impairments in popliteal endothelial-dependent vasodilator or vasoconstrictor responses following prolonged sitting

An acute bout of prolonged sitting (PS) impairs the popliteal artery flow-mediated dilation (FMD) response. Despite equivocal reductions in mean shear rate, young women demonstrate an attenuated decline in popliteal FMD versus young men. However, it is uncertain whether popliteal endothelial-dependent vasoconstrictor responses [low-flow-mediated constriction (L-FMC)] are similarly affected by PS and/or whether sex differences exist. We tested the hypothesis that women would have attenuated reductions in both popliteal FMD and L-FMC responses following an acute bout of PS. Popliteal FMD and L-FMC responses were assessed via duplex ultrasonography before and after a 3-h bout of PS. These responses were then compared between 10 men (24 ± 2 yr) and 10 women (23 ± 2 yr) with similar (P > 0.13) levels of objectively measured habitual physical activity (via PiezoRx) and sedentary time (via activPAL). At baseline, men and women exhibited similar (P > 0.46) popliteal FMD (4.8 ± 1.2 vs. 4.5 ± 0.6%) and L-FMC (-1.7 ± 1.0 vs. -1.9 ± 0.9%) responses. Both sexes experienced identical (group: P > 0.76; time: P < 0.001) PS-induced impairments in popliteal FMD (-2.8 ± 1.4 vs. -2.6 ± 0.9%) and L-FMC (1.3 ± 0.7% vs. 1.4 ± 0.7%). In young adults, sex did not influence the negative PS-induced FMD, L-FMC, or microvascular responses in the lower limb. As such, our findings suggest that young men and women are similarly susceptible to the acute negative vascular effects of PS. Future studies should extend these findings to older, less physically active adults and/or patients with vascular disease.NEW & NOTEWORTHY We compared changes in popliteal artery endothelial function to a single 3-h bout of sitting between young men and women. Both groups exhibited similar endothelial-dependent vasodilation (i.e., flow-mediated dilation) and endothelial-dependent vasoconstrictor responses (i.e., low-flow-mediated constriction) at baseline and equivocal impairments in these measures of endothelial function following prolonged sitting. These findings demonstrate that acute impairments in conduit artery endothelial health associated with uninterrupted sitting are not influenced by sex in young, healthy adults.

Changes in brachial artery endothelial function and resting diameter with moderate-intensity continuous but not sprint interval training in sedentary men.

Moderate-intensity continuous training (MICT) improves peripheral artery function in healthy adults, a phenomenon that reverses as continued training induces structural remodeling. Sprint interval training (SIT) elicits physiological adaptations similar to MICT, despite a lower exercise volume and time commitment; however, its effect on peripheral artery function and structure is largely unexplored. We compared peripheral artery responses to 12 wk of MICT and SIT in sedentary, healthy men (age = 27 ± 8 yr). Participants performed MICT (45 min of cycling at 70% peak heart rate; n = 10) or SIT (3 × 20-s "all out" cycling sprints with 2 min of recovery; n = 9), and responses were compared with a nontraining control group (CTL, n = 6). Allometrically scaled brachial flow-mediated dilation (FMD) increased 2.2% after 6 wk of MICT and returned to baseline levels by 12 wk, but did not change in SIT or CTL (group × time interaction, P = 0.04). Brachial artery diameter increased after 6 and 12 wk (main effect, P = 0.03), with the largest increases observed in MICT. Neither training protocol affected popliteal relative FMD and diameter, or central and lower limb arterial stiffness (carotid distensibility, central and leg pulse wave velocity) (P > 0.05 for all). Whereas earlier and more frequent measurements are needed to establish the potential presence and time course of arterial responses to low-volume SIT, our findings suggest that MICT was superior to the intense, but brief and intermittent SIT stimulus at inducing brachial artery responses in healthy men.NEW & NOTEWORTHY We compared the effects of 12 wk of moderate-intensity continuous training (MICT) and sprint interval training (SIT) on peripheral artery endothelial function and diameter, and central and lower limb stiffness in sedentary, healthy men. Whereas neither training program affected the popliteal artery or stiffness indexes, we observed changes in brachial artery function and diameter with MICT but not SIT. Brachial artery responses to SIT may follow a different time course or may not occur at all.

Inter-limb changes in arterial function after intense cycling exercise.

We investigated whether muscle exercise, by inducing a subsequent local response, alters local and systemic arterial function differently. Eleven healthy volunteers (31±8 years) performed a 45-min cycling session at a heart rate corresponding to 10% above ventilatory threshold. Measurements were performed before and 45 min after exercise. Central and peripheral blood pressures were assessed by applanation tonometry and automatic sphygmomanometer, respectively. Brachial and popliteal arterial changes in diameter and blood flow were assessed using ultrasonography. The endothelium-dependent function was assessed simultaneously on brachial and popliteal arteries by flow-mediated dilation. Systolic blood pressure decreased significantly in both upper and lower limbs as well as centrally. Ankle-brachial index decreased significantly. Cross-sectional area and blood flow of popliteal and brachial arteries increased significantly. The increase in blood flow was higher in the brachial than in the popliteal artery, whereas diameter increase was of similar magnitude between the two arteries. When normalized with shear rate, brachial flow-mediated dilation was significantly greater, whereas popliteal flow-mediated dilation was similar post- vs. pre-exercise. After an acute bout of intense cycling, blood flow increase and endothelial function were greater in the non-exercised upper limb compared to the exercised lower limb, suggesting that anaerobic exercise blunts the enhancement of systemic endothelium-dependant vasodilation in active muscle beds.

Five days of reduced physical activity selectively impairs endothelial function of the inactive limbs

Chronic physical inactivity promotes the development of cardiovascular diseases. However, few data exist on the effects of short‐term reductions in daily ambulatory activity on vascular function, particularly at the cellular level. Thus, we studied popliteal and brachial artery flow mediated dilation (FMD) and measured plasma levels of endothelial microparticles (EMPs) shed from apoptotic and activated endothelial cells (CD31+/CD42b− and CD62E+ EMPs, respectively) at baseline and following 5 days of reduced daily steps (&lt;5,000 steps/day) in 6 healthy, recreationally active men (26±3 yrs). We hypothesized that popliteal FMD would be reduced and concentrations of EMPs would be increased with inactivity. Following inactivity, popliteal FMD decreased (baseline: 5.4±1.2 vs. inactivity: 1.9±1.0%, p=0.05), while brachial artery FMD was unchanged (baseline: 4.2±0.7 vs. inactivity: 5.6±1.0%, p=0.12). CD31+/CD42b− (1.3 ± 0.4 vs. 4.8 ± 2.7 per μL plasma) and CD62E+ (69.2 ± 52.0 vs. 14.7 ± 7.9 per μL plasma) EMPs were not significantly altered following inactivity. These preliminary findings suggest that the vascular consequences of reduced daily steps are primarily localized to the lower (inactive) limbs, although changes in systemic EMPs reflective of endothelial apoptosis (CD31+/CD42b− ) and activation (CD62E+) were not observed.Grants: AHA 12PRE12080242, NIH R01‐HL093167, T32‐AR048523

Evidence for reduced sympatholysis in leg resistance vasculature of healthy older women

Inhibition of a sympathetic stimulus (i.e., sympatholysis) during forearm exercise is reduced with age in women. This age-related alteration has not been characterized in the lower extremity vasculature of women, and the potential for blunting of the conduit artery dilatory response to a sudden increase in shear stress [flow-mediated dilation (FMD)] has not been examined in older adults of either sex. In the present study, we assessed popliteal artery diameter and velocity (Doppler ultrasound) in 16 young (23 +/- 1 yr) and 14 older (69 +/- 1 yr) women after 5 min of distal calf occlusion (FMD), 3 min of hand immersion in ice water [cold pressor test (CPT)], and 5 min of distal calf occlusion combined with hand immersion in ice water (FMD+CPT). Peak popliteal conductance after 5-min ischemia was not significantly different in young vs. older women. During the combined stimulus (FMD+CPT), the magnitude of vasoconstriction in the calf (reduction in peak popliteal artery conductance) was similar (5-8%), despite reduced resting adrenergic sensitivity to CPT [young (Y): -27.3 +/- 3.8%; older (O): -15.8 +/- 2.2%; P < 0.05] and blunted muscle sympathetic nerve activity responses to CPT (Y: 12.7 +/- 3.6 bursts/min; O: 7.8 +/- 2.5 bursts/min; P < 0.05) in older women. Popliteal FMD, normalized to the shear stimulus, was attenuated by 60-70% in older women. Peak popliteal diameter, measured during the combined stimulus (FMD+CPT), was blunted in young but not in older women (Y FMD: 5.5 +/- 0.1 mm; Y FMD+CPT: 5.4 +/- 0.1 mm; P = 0.03; O FMD: 5.8 +/- 0.2 mm; O FMD+CPT: 5.8 +/- 0.2 mm). These results confirm previous findings of diminished reactivity in the conduit arteries of older humans and provide the first evidence of reduced sympatholysis in the leg resistance vasculature of older women.

Endothelial function of the popliteal artery in patients with coronary artery disease

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case–control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.