Structural and Mechanical Properties of Human Superficial Femoral and Popliteal Arteries.

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions.

Quantitative and large-format histochemistry to characterize peripheral artery compositional gradients.

The femoropopliteal artery (FPA) is a long, flexible vessel that travels down the anteromedial compartment of the thigh as the femoral artery and then behind the kneecap as the popliteal artery. This artery undergoes various degrees of flexion, extension, and torsion during normal walking movements. The FPA is also the most susceptible peripheral artery to atherosclerosis and is where peripheral artery disease manifests in 80% of cases. The connection between peripheral artery location, its mechanical flexion, and its physiological or pathological biochemistry has been investigated for decades; however, histochemical methods remain poorly leveraged in their ability to spatially correlate normal or abnormal extracellular matrix and cells with regions of mechanical flexion. This study generates new histological image processing pipelines to quantitate tissue composition across high-resolution FPA regions-of-interest or low-resolution whole-section cross-sections in relation to their anatomical locations and flexions during normal movement. Comparing healthy ovine femoral, popliteal, and cranial-tibial artery sections as a pilot, substantial arterial contortion was observed in the distal popliteal and cranial tibial regions of the FPA which correlated with increased vascular smooth muscle cells and decreased elastin content. These methods aim to aid in the quantitative characterization of the spatial distribution of extracellular matrix and cells in large heterogeneous tissue sections such as the FPA. RESEARCH HIGHLIGHTS: Large-format histology preserves artery architecture. Elastin and smooth muscle content is correlated with distance from heart and contortion during flexion. Cell and protein analyses are sensitive to sectioning plane and image magnification.

An acute bout of prolonged sitting blunts popliteal endothelium-independent dilation in young, healthy adults.

A single bout of prolonged uninterrupted sitting increases oxidative stress, reduces popliteal blood flow-induced shear stress, and diminishes endothelium-dependent, flow-mediated dilation (FMD). The FMD response is also influenced by the sensitivity of vascular smooth muscle cells to nitric oxide (i.e., endothelium-independent dilation), which is also attenuated by elevated oxidative stress. However, it is currently unknown whether prolonged sitting impacts popliteal endothelium-independent dilation responses, which may uncover a novel mechanism associated with sitting-induced vascular dysfunction. This study tested the hypothesis that prolonged sitting attenuates both popliteal FMD and endothelium-independent, nitroglycerin-mediated dilation responses (NMD, 0.4 mg sublingual dose). Popliteal blood flow (mL/min), relative FMD (%), and NMD (%) were assessed via duplex ultrasonography before and after a ∼3-h bout of sitting in 14 young, healthy adults (8♀; 22 ± 2 yr). Prolonged sitting attenuated resting blood flow (57 ± 23 to 32 ± 16 mL/min, P < 0.001), relative FMD (4.6 ± 2.8% to 2.2 ± 2.5%; P = 0.001), and NMD (7.3 ± 4.0% to 4.6 ± 3.0%; P = 0.002). These novel findings demonstrate that both endothelium-dependent and independent mechanisms contribute to the adverse vascular consequences associated with prolonged bouts of sitting.NEW & NOTEWORTHY We demonstrate that lower-limb vascular smooth muscle function is attenuated in young, healthy adults after an acute bout of prolonged sitting. These data indicate that prolonged sitting-induced vascular dysfunction involves both endothelium-dependent and -independent mechanisms.

Sex and light physical activity impact popliteal, but not brachial artery flow-mediated dilation in physically active young adults.

When controlling for baseline diameter, males have greater brachial flow-mediated dilation (BA-FMD) responses than females. It is unclear whether sex differences in baseline diameter also influences popliteal FMD (POP-FMD), which may be impacted by cardiorespiratory fitness and physical activity levels. We hypothesized that males would exhibit greater BA-FMD and POP-FMD when allometrically scaled to baseline diameter. FMD (ultrasonography), cardiorespiratory fitness (indirect calorimetry), and objectively measured physical activity were assessed in males (n = 13; age, 23 ± 3 years; peak oxygen consumption, 48.0 ± 7.1 mL·kg-1·min-1) and females (n = 13; age, 24 ± 2 years; peak oxygen consumption, 36.8 ± 6.0 mL·kg-1·min-1). Both groups had similarly high levels of moderate-to-vigorous intensity physical activity (503 ± 174 vs. 430 ± 142 min·week-1, p = 0.25). However, males were more aerobically fit (p < 0.001) and females accumulated more light-intensity physical activity (182 ± 67 vs. 127 ± 53 min·week-1, p = 0.03). Relative and allometrically scaled BA-FMD were similar (both, p ≥ 0.09) between sexes. In contrast, relative (6.2% ± 1.0% vs. 4.6% ± 1.4%, p = 0.001) and scaled (6.8% ± 1.7% vs. 4.7% ± 1.7%, p = 0.03) POP-FMD were greater in females. Relative POP-FMD was related to light-intensity physical activity in the pooled sample (r = 0.43; p = 0.04). However, the enhanced relative POP-FMD in females remained after adjusting for higher light-intensity physical activity levels (p = 0.01). Young females have enhanced popliteal, but not brachial, endothelial health than males with similar moderate-to-vigorous intensity physical activity levels and higher cardiorespiratory fitness. Novelty In physically active adults, females had greater POP-FMD but not BA-FMD than males. The enhanced POP-FMD in females was not related to greater vascular smooth muscle sensitivity to nitric oxide or their smaller baseline diameters. POP-FMD was associated with light physical activity levels in the pooled sample.

Skeletal Muscle Microvascular Adaptations Following Regular Cold Water Immersion.

This study investigated the effect of endurance training and regular post-exercise cold water immersion on changes in microvascular function. Nine males performed 3 sessions∙wk-1 of endurance training for 4 weeks. Following each session, participants immersed one leg in a cold water bath (10°C; COLD) for 15 min while the contra-lateral leg served as control (CON). Before and after training, microvascular function of the gastrocnemius was assessed using near-infrared spectroscopy, where 5 min of popliteal artery occlusion was applied and monitored for 3 min upon cuff release. Changes in Hbdiff (oxyhemoglobin - deoxyhemoglobin) amplitude (O-AMP), area under curve (O-AUC) and estimated muscle oxygen consumption (mVO2) were determined during occlusion, while the reperfusion rate (R-RATE), reperfusion amplitude (R-AMP) and hyperemic response (HYP) were determined following cuff release. Training increased O-AMP (p=0.010), O-AUC (p=0.011), mVO2 (p=0.013), R-AMP (p=0.004) and HYP (p=0.057). Significant time (p=0.024) and condition (p=0.026) effects were observed for R-RATE, where the increase in COLD was greater compared with CON (p=0.026). In conclusion, R-RATE following training was significantly higher in COLD compared with CON, providing some evidence for enhanced microvascular adaptations following regular cold water immersion.

Impact of High-Intensity Interval Training, Moderate-Intensity Continuous Training, and Resistance Training on Endothelial Function in Older Adults.

PURPOSE: It is unclear if high-intensity interval training (HIIT) elicits superior improvements in brachial artery (BA) flow-mediated dilation (FMD) responses (i.e., endothelial-dependent vasodilation) than moderate-intensity continuous training (MICT) or resistance training (RT) in otherwise healthy older adults. Whether HIIT enhances lower-limb FMD responses and/or augments low flow-mediated constriction (L-FMC) (endothelial-dependent vasoconstriction) responses more than MICT or RT is also unknown. We tested the hypothesis that HIIT would improve BA and popliteal artery (POP) FMD and L-FMC responses more than MICT or RT in healthy older adults. METHODS: Thirty-eight older adults (age, 67 ± 6 yr) performed 6 wk of either HIIT (2 × 20 min bouts alternating between 15-s intervals at 100% of peak power output [PPO] and passive recovery [0% PPO]; n = 12), MICT (34 min at 60% PPO; n = 12), or whole-body RT (8 exercises, 2 × 10 repetitions; n = 14). The L-FMC and FMD were measured before and after training using high-resolution ultrasound and quantified as the percent change in baseline diameter during distal cuff occlusion and after cuff release, respectively. RESULTS: Resting BA blood flow and vascular conductance (both, P < 0.003) were greater after HIIT only. The HIIT and MICT similarly increased BA-FMD (pre-post: both, P < 0.001), but only HIIT improved BA L-FMC (P < 0.001). Both HIIT and MICT similarly enhanced POP FMD and L-FMC responses (both, P < 0.045). Resistance training did not impact FMD or L-FMC responses in either artery (all, P > 0.20). CONCLUSIONS: HIIT and MICT, but not RT, similarly improved lower-limb vasodilator and vasoconstrictor endothelial function in older adults. Although HIIT and MICT groups enhanced BA vasodilator function, only HIIT improved resting conductance and endothelial sensitivity to low-flow in the BA. In the short-term, HIIT may be most effective at improving peripheral vascular endothelial function in older adults.

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.

Relationship between brachial and popliteal artery low-flow-mediated constriction in older adults: impact of aerobic fitness on vascular endothelial function.

We previously observed that brachial artery (BA) low-flow-mediated constriction (L-FMC) is inversely related to aerobic fitness (i.e., V̇o2peak) in older adults (OA). However, it is unclear if an L-FMC response is elicited in the popliteal artery (POP) or if a similar inverse relationship with aerobic fitness exists. Considering that the POP experiences larger shear stress fluctuations during sedentary behaviors and traditional lower limb modes of aerobic exercise, we tested the hypotheses that 1) heterogeneous L-FMC responses exist between the BA versus POP of OA, and 2) that aerobic fitness will be inversely related to POP L-FMC. L-FMC was assessed in 47 healthy OA (30 women, 67 ± 5 yr) using duplex ultrasonography and quantified as the percent decrease in diameter (from baseline) during the last 30 s of a 5-min distal cuff occlusion period. When allometrically scaled to baseline diameter, the BA exhibited a greater L-FMC response than the POP (-1.3 ± 1.6 vs. -0.4 ± 1.6%; P = 0.03). Furthermore, L-FMC responses in the BA and POP were not correlated (r = 0.22; P = 0.14). V̇o2peak was strongly correlated to POP L-FMC (r = -0.73; P < 0.001). The heterogeneous BA versus POP L-FMC data indicate that upper limb L-FMC responses do not represent a systemic measure of endothelial-dependent vasoconstrictor capacity in OA. The strong association between V̇o2peak and POP L-FMC suggests that localized shear stress patterns, perhaps induced by lower limb dominant modes of aerobic exercise, may result in greater vasoconstrictor responsiveness in healthy OA. NEW & NOTEWORTHY We compared low-flow-mediated constriction responses between the brachial and popliteal arteries of healthy older adults. Vasoconstrictor responses were not correlated between arteries. A strong relationship between aerobic fitness and low-flow-mediated vasoconstriction was observed in the popliteal artery. These findings suggest that brachial vasoconstrictor responsiveness is not reflective of the popliteal artery, which is exposed to larger shear stress fluctuations during bouts of sedentary behavior and traditional lower limb modes of exercise.

The relationship between patellofemoral arthritis and fat tissue volume, body mass index and popliteal artery intima-media thickness through 3T knee MRI

Background/aim: Evaluating the relationship of patellar chondromalacia with obesity, infrapatellar fat pad (IFP) volume and popliteal artery intima-media thickness (IMT). Materials and methods: A total of203 patients with different degree of patellar chondromalacia (103 male, 100 female) and 52 control subjects (19 male, 33 female) were included and grouped according to sex, age, body surface area (BSA), body mass index (BMI) and patellar chondromalacia classification. All measurements were completed with 3T magnetic resonance imaging (MRI). Articular cartilage and IFP volume were measured in saggital plane using double echo steady state (DESS) and DIXON sequences, respectively. Patellar cartilage damage was graded using modified outerbridge classification, and the relations among cartilage volume and BMI, BSA, IFP, IMT were statistically assessed. Results: Popliteal artery IMT showed an independent association with the prevalence of cartilage defects and IFP volumes (P ˂ 0.001). There was an association between BMI and IFP volumes (P ˂ 0.001). However, no differences were observed between IFP volume and different chondromalacia groups. When IFP measurements were corrected using individual BMI and BSA values, a positive correlation was found between control and advanced chondromalacia groups (P ˂ 0.001). Conclusion: This study demonstrates the relationship among obesity, IMT and chondromalacia and highlights this potential circle to develop effective treatments and inhibit the progression of chondromalacia.

An Animal Model of Human Peripheral Arterial Bending and Deformation.

BACKGROUND: Designing peripheral arterial stents has proved challenging, as implanted devices will repetitively and unpredictably deform and fatigue during movement. Preclinical testing is often inadequate, given the lack of relevant animal models. The purpose of this study was to test the hypothesis that deformation of the human peripheral vasculature could be qualitatively and quantitatively modeled using an experimental animal. METHODS: Anteroposterior contrast angiography was performed in domestic Landrace-Yorkshire farm pigs. Images were obtained with the hind limbs naturally extended then repeated, (1) flexed approximately 90° at the hip and knee, (2) overflexed in a nonphysiological fashion. Quantitative vascular angiographic analysis was utilized to measure arterial diameter, length, and deformation. Percent axial arterial compression and bending were assessed. RESULTS: Eight iliofemoral arteries in four animals were imaged. Mean luminal diameters of the iliac and femoral segments in the neutral position were 5.4 ± 0.5 mm and 4.6 ± 0.5 mm. Hind limb physiologic flexion induced profound arterial compression, 17 ± 8% and 29 ± 6% and bending, 36°±10° and 76° ± 13° within the iliac and femoral segments, respectively. With extreme flexion, the femoral artery could be reliably bent >90°. The observed findings exceeded the deformation observed historically within the human superficial femoral (∼5% compression and 10° bending) and popliteal artery (∼10% compression and 70° bending). CONCLUSIONS: Significant nonradial deformation of the porcine iliofemoral arteries was observed during manual hind limb flexion and exceeded that typically observed in humans. This model constitutes a "worst case" scenario for testing deformation and fatigue of intravascular devices indicated for the human peripheral vasculature.

Decline of popliteal artery flow-mediated dilation with aging and possible involvement of asymmetric dimethylarginine in healthy men.

PURPOSE: We examined the influences of age and gender on flow-mediated endothelial function and the involvement of the competitive inhibition of L-arginine in endothelial function. METHODS: We measured brachial and popliteal flow-mediated vasodilation (FMD) responses, nitrate/nitrite (NOx) concentrations, and plasma levels of asymmetric dimethylarginine (ADMA) in four healthy, nonsmoking groups: young men (mean 26 ± 2 years, n = 17), middle-aged men (mean 50 ± 3 years, n = 19), young women (mean 27 ± 2 years, n = 16), and middle-aged women (mean 51 ± 2 years, n = 18). RESULTS: In young men, we found no significant differences between brachial and popliteal artery FMDs (10.6 ± 1.5 vs 8.7 ± 1.6%, p = 0.06). However, the popliteal artery FMD was significantly lower than the brachial artery FMD in middle-aged men (11.4 ± 1.5 vs 6.4 ± 1.0%, p < 0.001). In women, we found no significant differences between brachial and popliteal artery FMDs in young and middle-aged individuals (young, p = 0.17; middle-aged, p = 0.08). Popliteal artery FMD correlated with plasma NOx and ADMA levels as well as with the NOx/ADMA ratio in men but not in women (r = 0.485, - 0.544, and 0.672, respectively). CONCLUSION: We concluded that a decrease in flow-mediated endothelial function in arteries of the lower extremities was evident in healthy middle-aged men, but not in middle-aged women. The competitive inhibition of L-arginine may contribute to this decrease in men.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Increased endothelial shear stress improves insulin-stimulated vasodilatation in skeletal muscle.

KEY POINTS: It has been postulated that increased blood flow-associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin-stimulated vasodilatation. This report provides evidence supporting the hypothesis that increased shear stress exerts insulin-sensitizing effects in the vasculature and this evidence is based on experiments in vitro in endothelial cells, ex vivo in isolated arterioles and in vivo in humans. Given the recognition that vascular insulin signalling, and associated enhanced microvascular perfusion, contributes to glycaemic control and maintenance of vascular health, strategies that stimulate an increase in limb blood flow and shear stress have the potential to have profound metabolic and vascular benefits mediated by improvements in endothelial insulin sensitivity. ABSTRACT: The vasodilator actions of insulin contribute to glucose uptake by skeletal muscle, and previous studies have demonstrated that acute and chronic physical activity improves insulin-stimulated vasodilatation and glucose uptake. Because this effect of exercise primarily manifests in vascular beds highly perfused during exercise, it has been postulated that increased blood flow-associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin-stimulated vasodilatation. Accordingly, herein we tested the hypothesis that increased shear stress, in the absence of muscle contraction, can acutely render the vascular endothelium more insulin-responsive. To test this hypothesis, complementary experiments were conducted using (1) cultured endothelial cells, (2) isolated and pressurized skeletal muscle arterioles from swine, and (3) humans. In cultured endothelial cells, 1 h of increased shear stress from 3 to 20 dynes cm-2 caused a significant shift in insulin signalling characterized by greater activation of eNOS relative to MAPK. Similarly, isolated arterioles exposed to 1 h of intraluminal shear stress (20 dynes cm-2 ) subsequently exhibited greater insulin-induced vasodilatation compared to arterioles kept under no-flow conditions. Finally, we found in humans that increased leg blood flow induced by unilateral limb heating for 1 h subsequently augmented insulin-stimulated popliteal artery blood flow and muscle perfusion. In aggregate, these findings across models (cells, isolated arterioles and humans) support the hypothesis that elevated shear stress causes the vascular endothelium to become more insulin-responsive and thus are consistent with the notion that shear stress may be a principal mechanism by which physical activity enhances insulin-stimulated vasodilatation.

Aerobic Exercise Improves Microvascular Function in Older Adults.

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. PURPOSE: The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training. METHODS: Twenty-three sedentary older adults (67 ± 5 yr, body mass index = 29 ± 5, mean ± SD) successfully completed a randomized 12-wk graded treadmill walking intervention. The exercise group (EX) performed 40 min of uphill walking 4 d·wk at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 wk. Blood oxygen level-dependent (BOLD) responses of the soleus measured by magnetic resonance imaging were used to evaluate microvascular function; brief (1 s) maximal plantarflexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound after brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity, and whole-body peak oxygen consumption (V˙O2peak) was used to confirm training-induced cardiorespiratory adaptations. RESULTS: Peak postcontraction BOLD response increased by 33% in EX (PRE, 3.3% ± 1.0%; POST, 4.4% ± 1.4%) compared with CON (PRE, 3.0% ± 1.3%; POST, 3.2% ± 1.5%), P < 0.05. EX with hypertension tended to show a blunted peak BOLD increase (n = 6, 15%) compared with EX normotensive (n = 7, 50%), P = 0.056. Peak postcontraction blood flow increased by 39% in EX (PRE, 217 ± 88 mL·min; POST, 302 ± 167 mL·min) compared with CON (PRE, 188 ± 54 mL·min; POST, 184 ± 44 mL·min), P < 0.05. EX muscle oxidative capacity (kPCr) improved by 40% (PRE, 1.60 ± 0.57 min; POST, 2.25 ± 0.80 min) compared with CON (PRE, 1.69 ± 0.28 min; POST, 1.76 ± 0.52 min), P < 0.05. V˙O2peak increased by 9% for EX (PRE, 19.0 ± 3.1 mL·kg·min; POST, 20.8 ± 2.9 mL·kg·min) compared with a 7% loss in CON (PRE, 21.9 ± 3.6 mL·kg·min; POST, 20.4 ± 3.5 mL·kg·min), P < 0.05. CONCLUSION: Moderate aerobic exercise significantly improved microvascular function of the leg in older adults.

Acute Lower Leg Heating Increases Exercise Capacity in Patients With Peripheral Artery Disease.

BACKGROUND/OBJECTIVE: In this pilot study, we tested the hypothesis that acute lower leg heating (LLH) increases postheating popliteal artery blood flow and 6-minute walk distance in patients with peripheral artery disease (PAD). METHODS: Six patients (5 male, 1 female) with PAD (69 ± 6.9 years; claudication: ankle-brachial index < 0.90) participated in 3 randomized treatment sessions (2-7 days apart): control or bilateral LLH conducted via water bath immersion (42°C; ~40-cm depth) for either 15 or 45 minutes. Popliteal artery blood flow (Doppler ultrasound) and arterial pressure were measured before and after LLH. Six-minute walk distance was measured on the control day and each experimental day 35 minutes post-LLH. RESULTS: Popliteal artery blood flow increased after heating in a duration-dependent manner (P < .05, postheating vs control for both heating conditions and between them). Six-minute walk distance increased by 10% and 12% after 15- and 45-minute heating treatments, respectively (P < .05 vs control session). CONCLUSIONS: Lower leg heating, for as short as 15 minutes, increases postheating leg perfusion and exercise capacity in patients with PAD.

Natural remodeling of the distal anastomosis of an above-knee femoropopliteal bypass depicted by CT angiography of lower limbs improves geometry of the reconstruction.

The geometry of the distal anastomosis of a femoropopliteal bypass influences local hemodynamics and formation of intimal hyperplasia. We hypothesized that the distal anastomosis of an above-knee femoropopliteal bypass undergoes remodeling that results in displacement of the original course of the popliteal artery and change in the anastomosis angle. We identified 43 CT angiography examination with proximal femoropopliteal bypass and either a preserved contralateral popliteal artery or previous CTA before construction of the bypass for comparison. In these examinations, we measured the displacement distance and angle at the level of the distal anastomosis and compared these measurements with clinical and imaging data. The displacement distance was 8.8+/-4.9 mm (P<0.0001) and the displacement angle was -1° (IQR=44°). The angle between the inflow and outflow artery was 153+/-16° (P<0.0001). There was a negative association between the displacement angle and the angle between the bypass and the outflow artery (r=-0.318, P=0.037). Patients with reversed venous grafts had a greater displacement of the anastomosis (14.7+/-3.0 mm) than patients with prosthetic grafts (8.0+/-4.5 mm, P=0.0011). We conclude that construction of a distal anastomosis of proximal femoropopliteal bypass results in displacement of the original course of the popliteal artery towards the bypass and this effect is more pronounced in reversed venous grafts.

Brief periods of inactivity reduce leg microvascular, but not macrovascular, function in healthy young men.

NEW FINDINGS: What is the central question of this study? We aimed to examine leg vascular responses to brief periods of inactivity. What is the main finding and its importance? We demonstrate that a mere 10 min of sitting is sufficient to impair leg microvascular function (reactive hyperaemia). However, conduit artery vasodilatation (flow-mediated dilatation) was unaffected, indicating maintained macrovascular function. Interestingly, immobile supine rest also resulted in a reduction in microvascular function alone that was prevented when calf muscle contractions were performed. Collectively, these data highlight the susceptibility of the microcirculation to short periods of inactivity and the beneficial role of skeletal muscle contraction for vascular health. ABSTRACT: Prolonged sitting for 1-6 h has been shown to impair leg macrovascular [i.e. reduced flow-mediated dilatation (FMD)] and microvascular (i.e. reduced reactive hyperaemia) function. These impairments appear to be mediated through reductions in shear stress. Interestingly, a reduction in shear rate has been observed as early as 10 min into sitting. However, it is unknown whether this acute reduction in shear stress is sufficient to affect vascular function. Accordingly, we studied 18 young men and assessed popliteal artery FMD and reactive hyperaemia before (Baseline) and after (PostSit) a 10 min sitting period. Popliteal artery shear rate was significantly reduced during sitting (Baseline, 62 ± 35 s-1 ; 10 min sitting, 27 ± 13 s-1 ; P < 0.001). Macrovascular function was unaffected by 10 min of sitting (Baseline, 4.4 ± 2.1%; PostSit, 4.3 ± 2.3%; P = 0.97), but microvascular function was reduced (Baseline, 4852 ± 2261 a.u.; PostSit, 3522 ± 1872 a.u.; P = 0.02). In a subset of individuals, we extended the recovery period after sitting and demonstrated that resting shear rate and reactive hyperaemia responses remained low up to 1 h post-sitting (P < 0.001), whereas FMD was unchanged throughout (P = 0.99). Additionally, time control experiments were performed with participants in an immobile supine position, which demonstrated no change in macrovascular function (P = 0.94) but, unexpectedly, a reduction in microvascular function (P = 0.008). Importantly, when calf muscle contractions were performed during supine rest, reactive hyperaemia responses were maintained (P = 0.76), along with FMD (P = 0.88). These findings suggest that the leg microcirculation might be more vulnerable to short periods of inactivity, whereas conduit artery vasodilatation appears well maintained. Moreover, intermittent skeletal muscle contractions are beneficial for microvascular function.

Achieving Canadian physical activity guidelines is associated with better vascular function independent of aerobic fitness and sedentary time in older adults.

Canadian physical activity guidelines recommend older adults accumulate 150 min of weekly moderate to vigorous physical activity (MVPA). Older adults who are insufficiently active may have reduced blood vessel health and an increased risk of cardiovascular disease. We tested this hypothesis in 11 older adults who did (7 female; age, 65 ± 5 years; MVPA, = 239 ± 81 min/week) and 10 older adults who did not (7 female; age, 68 ± 9 years; MVPA, 95 ± 33 min/week) meet MVPA guidelines. Flow-mediated dilation (FMD) in the brachial (BA) and popliteal (POP) arteries, as well as nitroglycerin-mediated dilation (NMD; endothelial-independent dilation) in the POP were assessed via ultrasonography. Aerobic fitness (peak oxygen uptake) was determined using a graded, maximal cycle ergometry test via indirect calorimetry. MVPA and sedentary time were assessed over 5 days using the PiezoRx and activPAL, respectively. There were no differences in peak oxygen uptake (26 ± 10 vs. 22 ± 10 mL O2/(kg·min); p = 0.26) or sedentary time (512 ± 64 vs. 517 ± 76 min/day; p = 0.87) between groups; however, those who achieved the MVPA guidelines had a higher BA-FMD (5.1% ± 1.3% vs. 3.6% ± 1.7%; p = 0.03), POP-FMD (2.6% ± 1.1% vs. 1.3% ± 0.8%; p = 0.006), and POP-NMD (5.1% ± 1.7% vs. 3.3% ± 2.1%; p = 0.04). In the pooled sample, MVPA was moderately correlated to both BA-FMD (r = 0.53; p = 0.01) and POP-NMD (r = 0.59; p = 0.005), and strongly correlated to POP-FMD (r = 0.85; p < 0.001). Collectively, our results provide supporting evidence that meeting MVPA guidelines is associated with better vascular function and may reduce the risk of developing cardiovascular disease in older adults. Furthermore, these data suggest that weekly MVPA time may have a greater impact on blood vessel function than aerobic fitness and weekly sedentary time.

Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on Older Adults' Cardiovascular Profile: Part 2-Isotemporal Substitution Approach.

BACKGROUND: The aim of the study was to provide an isotemporal substitution model to predict how changes in physical behavior may affect the cardiovascular parameters (CVPs) of older adults. METHODS: Participants wore a thigh-mounted accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal artery was conducted using ultrasound. Isotemporal substitution was used to simulate the degree to which replacing 1 hour of physical behavior with another would affect CVP. RESULTS: Substitution of sedentary behavior with Standing and sporadic moderate- to vigorous-intensity physical activity (MVPA accumulated in bouts <10 min) would reduce resting heart rate [-6.20 beats per minute (-12.1 to -0.22) and -3.72 beats per minute (-7.01 to -0.44), respectively]. Substitution of sedentary behavior with light-intensity physical activity would reduce carotid artery diameter [-0.54 mm (-1.00 to -0.07)]. Substitution of Standing with sporadic MVPA would increase popliteal artery diameter [1.31 mm (0.11 to 2.51)]. CONCLUSIONS: Our modeling suggests that an accumulation of MVPA bouts that are shorter than the recommended 10-minute minimum may still improve CVP, with lower intensity physical activity also influencing CVP. Our findings are a promising avenue for lifestyle interventions in older adults to reduce the aging effects on CVP for those who cannot engage or sustain sufficient MVPA.