Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity

The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA ( r = 0.57 and r = 0.66) and SFA ( r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA ( r = 0.38 and r = 0.35) and SFA ( r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

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CORP: Ultrasound assessment of vascular function with the passive leg movement technique

Journal of Applied Physiology ◽

10.1152/japplphysiol.00557.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1708-1720 ◽

Cited By ~ 22

Author(s):

Jayson R. Gifford ◽

Russell S. Richardson

Keyword(s):

Vascular Function ◽

Cardiovascular Health ◽

Vascular System ◽

The Elderly ◽

Passive Movement ◽

Flow Mediated Dilation ◽

Peripheral Vascular ◽

Ultrasound Assessment ◽

Leg Movement ◽

Hyperemic Response

As dysfunction of the vascular system is an early, modifiable step in the progression of many cardiovascular diseases, there is demand for methods to monitor the health of the vascular system noninvasively in clinical and research settings. Validated by very good agreement with more technical assessments of vascular function, like intra-arterial drug infusions and flow-mediated dilation, the passive leg movement (PLM) technique has emerged as a powerful, yet relatively simple, test of peripheral vascular function. In the PLM technique, the change in leg blood flow elicited by the passive movement of the leg through a 90° range of motion is quantified with Doppler ultrasound. This relatively easy-to-learn test has proven to be ≤80% dependent on nitric oxide bioavailability and is especially adept at determining peripheral vascular function across the spectrum of cardiovascular health. Indeed, multiple reports have documented that individuals with decreased cardiovascular health such as the elderly and those with heart failure tend to exhibit a substantially blunted PLM-induced hyperemic response (~50 and ~85% reduction, respectively) compared with populations with good cardiovascular health such as young individuals. As specific guidelines have not yet been put forth, the purpose of this Cores of Reproducibility in Physiology (CORP) article is to provide a comprehensive reference for the assessment and interpretation of vascular function with PLM with the aim to increase reproducibility and consistency among studies and facilitate the use of PLM as a research tool with clinical relevance.

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Single passive leg movement assessment of vascular function: contribution of nitric oxide

Journal of Applied Physiology ◽

10.1152/japplphysiol.00533.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1468-1476 ◽

Cited By ~ 16

Author(s):

Ryan M. Broxterman ◽

Joel D. Trinity ◽

Jayson R. Gifford ◽

Oh Sung Kwon ◽

Andrew C. Kithas ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Function ◽

Clinical Utility ◽

Area Under The Curve ◽

Vasodilatory Response ◽

Novel Approach ◽

Movement Assessment ◽

No Bioavailability ◽

Leg Movement

The assessment of passive leg movement (PLM)-induced leg blood flow (LBF) and vascular conductance (LVC) is a novel approach to assess vascular function that has recently been simplified to only a single PLM (sPLM), thereby increasing the clinical utility of this technique. As the physiological mechanisms mediating the robust increase in LBF and LVC with sPLM are unknown, we tested the hypothesis that nitric oxide (NO) is a major contributor to the sPLM-induced LBF and LVC response. In nine healthy men, sPLM was performed with and without NO synthase inhibition by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). Doppler ultrasound and femoral arterial pressure were used to determine LBF and LVC, which were characterized by the peak change (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCAUC). l-NMMA significantly attenuated ΔLBFpeak [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBFAUC [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVCpeak [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min−1·mmHg−1], and LVCAUC [0.5 ± 0.3 (l-NMMA) vs. 1.6 ± 0.9 (control) ml/mmHg]. The magnitude of the NO contribution to LBF and LVC was significantly correlated with the magnitude of the control responses ( r = 0.94 for ΔLBFpeak, r = 0.85 for LBFAUC, r = 0.94 for ΔLVCpeak, and r = 0.95 for LVCAUC). These data establish that the sPLM-induced hyperemic and vasodilatory response is predominantly (~65%) NO-mediated. As such, sPLM appears to be a promising, simple, in vivo assessment of NO-mediated vascular function and NO bioavailability. NEW & NOTEWORTHY Passive leg movement (PLM), a novel assessment of vascular function, has been simplified to a single PLM (sPLM), thereby increasing the clinical utility of this technique. However, the role of nitric oxide (NO) in mediating the robust sPLM hemodynamic responses is unknown. This study revealed that sPLM induces a hyperemic and vasodilatory response that is predominantly NO-mediated and, as such, appears to be a promising simple, in vivo, clinical assessment of NO-mediated vascular function and, therefore, NO bioavailability.

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Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response

Journal of Applied Physiology ◽

10.1152/japplphysiol.00806.2016 ◽

2017 ◽

Vol 122 (1) ◽

pp. 28-37 ◽

Cited By ~ 15

Author(s):

Massimo Venturelli ◽

Gwenael Layec ◽

Joel Trinity ◽

Corey R. Hart ◽

Ryan M. Broxterman ◽

...

Keyword(s):

Vascular Function ◽

Knee Flexion ◽

Assessment Method ◽

Peripheral Stimulus ◽

Clinical Role ◽

Chronotropic Response ◽

Novel Approach ◽

Leg Movement ◽

Flexion And Extension ◽

Function Assessment

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min−1·mmHg−1, respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min−1·mmHg−1, respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically. NEW & NOTEWORTHY Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more useful clinically.

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Abstract 153: Automated Angiographic Assessment Of Coronary Artery Vasomotion In Kawasaki Disease Patients

Circulation ◽

10.1161/circ.131.suppl_2.153 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Mitchel Benovoy ◽

Farida Cheriet ◽

Roch L Maurice ◽

Nagib Dahdah

Keyword(s):

Health Assessment ◽

Assessment System ◽

Vascular Health ◽

Pressure Gradients ◽

Intracoronary Imaging ◽

Temporal Tracking ◽

Vascular Physiology ◽

The Mean ◽

Spatio Temporal ◽

Stiffness Characteristics

Background: Mechanical properties of coronary arteries (CA) hold clues to vascular health and viability. Traditionally assessed with intracoronary imaging, we present an angiography-based system to assess CA vasomotion using automatic vessel segmentation and spatio-temporal tracking. Elastic moduli computed from dynamic CA calibers are compared between non-KD patients (CTL), KD patients with no CA aneurysms (KDAN-), and those with aneurysms (KDAN+). Methods: Proximal CA angiograms are automatically segmented and tracked over a cardiac cycle. CA centerline is extracted and the mean caliber is computed from diameters along its length. The resulting caliber variation reflects the CA vasomotion (Figure 1a). We then calculated the Vasomotion Standard Deviation (VSD) and CA recoil with the mean constriction velocity (MCV). Finally, Elastic Pressure moduli were computed using trans-myocardium pressure gradients. Results: We analyzed 51 left CA segments from 23 patients (5 CTL, 5 KDAN-, 13 KDAN+). Data are mean ± SD normalized pixels (npx). VSD was significantly reduced ( p <0.01) in KDAN+ (0.25±0.05) and KDAN- (0.27±0.04) vs CTL (0.38±0.07 npx). Coronary recoil was significantly reduced (p<0.05) in KDAN+ vs CTL, with MCV 3.50±0.67 vs 4.59±1.94 npx/sec. Pressure-dependent stiffness characteristics were equally atypical (Figure 1b). Conclusion: The proposed angiography-based stiffness assessment system shows abnormal CA vascular physiology in our cohort of KD patients. These results concur with previous invasive studies. The potential usability of this system for vascular health assessment could be applied to previously recorded CA angiograms for risk stratification.

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The passive leg movement technique for assessing vascular function: the impact of baseline blood flow

Experimental Physiology ◽

10.1113/ep089818 ◽

2021 ◽

Vol 106 (10) ◽

pp. 2133-2147

Author(s):

Katherine L. Shields ◽

Ryan M. Broxterman ◽

Catherine L. Jarrett ◽

Angela V. Bisconti ◽

Soung Hun Park ◽

...

Keyword(s):

Blood Flow ◽

Vascular Function ◽

Leg Movement ◽

The Impact

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Abstract 16530: Post-exercise Flow-mediated Dilation is augmented in Highly Trained Female Athletes

Circulation ◽

10.1161/circ.132.suppl_3.16530 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Daniela K Andaku ◽

Bruno Archiza ◽

Flavia C Caruso ◽

Katiany T Zangrando ◽

Humberto Lanzotti ◽

...

Keyword(s):

Flow Velocity ◽

Brachial Artery ◽

Vascular Function ◽

Female Athletes ◽

Maximal Exercise ◽

High Volume ◽

Flow Mediated Dilation ◽

Brachial Artery Diameter ◽

Arterial Function ◽

Training History

Background: Recent evidence has indicated a ceiling to the benefits of exercise training that, if chronically surpassed, may have a negative effect on cardiac function. Conversely, improvements in peripheral arterial function may respond positively to chronic high volume training. Recent studies have shown that flow-mediated dilation (FMD) is decreased immediately after maximal exercise in sedentary subjects and is unaltered in subjects who participate in moderate volume exercise. We investigated the acute effects of maximal exercise on vascular function of elite female athletes with a high-volume training history. Methods: Fifteen elite female soccer players (mean age: 22.1 ± 4.4 years; BMI: 20.76 ± 1.75 kg/m2), with a high volume/intensity training history (4-6 hours per day) were evaluated. Subjects underwent maximal cardiopulmonary exercise testing (CPX) on a treadmill (VO2max 41.1 ± 3.9 mLO2•kg-1•min-1). Brachial artery FMD was determined using high-resolution ultrasound before and immediately after CPX. Flow velocity were measured at baseline (BSL) and during reactive hyperemia (RH) both prior to and following exercise. Results: Brachial artery diameter increased during RH before (3.42 ± 0.38mm vs. 3.03 ± 0.28mm, p<0.001) and after CPX (3.61 ± 0.44mm vs. 3.10 ± 0.37mm, p<0.001). Importantly, FMD was increased following CPX compared to BSL (16.86 ± 9.04% vs. 12.95 ± 7.03%, p=0.027). There was significant increase in peak flow velocity during RH before (135.28 ± 42.19cm/s vs. 79.19 ± 28.14cm/s, p=0.001) and after CPX (139.15 ± 41.07cm/s vs. 87.64 ± 21.23cm/s, p<0.001) (Table). Conclusion: The results of the current study indicate that arterial function is improved following acute aerobic exercise in elite female athletes with a chronic high volume training history. These findings deviate from the emerging literature suggesting chronic high volume training may be detrimental to cardiovascular function in the long term.

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The passive leg movement technique for assessing vascular function: defining the distribution of blood flow and the impact of occluding the lower leg

Experimental Physiology ◽

10.1113/ep087845 ◽

2019 ◽

Vol 104 (10) ◽

pp. 1575-1584 ◽

Cited By ~ 2

Author(s):

Katherine L. Shields ◽

Ryan M. Broxterman ◽

Catherine L. Jarrett ◽

Angela V. Bisconti ◽

Soung Hun Park ◽

...

Keyword(s):

Blood Flow ◽

Vascular Function ◽

Lower Leg ◽

Leg Movement ◽

The Impact

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Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00208.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. H192-H202

Author(s):

Alexander B. Hansen ◽

Gilbert Moralez ◽

Steven A. Romero ◽

Christopher Gasho ◽

Michael M. Tymko ◽

...

Keyword(s):

Skeletal Muscle ◽

Adrenergic Receptors ◽

Whole Body ◽

Cycle Exercise ◽

Vascular Conductance ◽

Hand Grip ◽

Vasodilatory Response ◽

Sympathetic Vasoconstriction ◽

Exercise Induced

Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.

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Study of endothelial function in pregnant women with gestational diabetes mellitus by flow mediated dilation of brachial artery

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20202315 ◽

2020 ◽

Vol 9 (6) ◽

pp. 2377

Author(s):

Nidhi Pandey ◽

Poonam Goel ◽

Anita Malhotra ◽

Reeti Mehra ◽

Navjot Kaur

Keyword(s):

Gestational Diabetes ◽

Endothelial Function ◽

Pregnant Women ◽

Brachial Artery ◽

Vascular Function ◽

Post Partum ◽

Control Group ◽

Flow Mediated Dilation ◽

The Mean ◽

The Difference

Background: The objective of the study was to assess vascular function in normal pregnant women and women with gestational diabetes and to study its temporal relationship with gestational age at 24-28-week POG and at 36-38-week POG and changes in FMD in postpartum period.Methods: Assessment of vascular function was done at 24-28-week POG, 36-38-week POG and at 6-12-week postpartum by flow mediated dilation of brachial artery in 37 healthy pregnant women and 37 pregnant women with GDM.Results: In GDM group mean FMD at 24-28 weeks of POG, at 36-38 weeks POG was lower as compared to the control group (11.225±6.20,8.464±6.09 versus 14.49±5.21, 10.898±4.12) although the difference in mean FMD in two groups was not statistically significant. It was found that the decrease in FMD at 36-38-week POG as compared to 24-28 weeks POG was statistically significant in both the groups (p<0.001).Conclusions: This study revealed that when endothelial function as assessed by FMD was compared at different period of gestation, the mean decrease in FMD at 36-38-week POG as compared to 24-28-week POG and 6-week post-partum was statistically significant in patients with GDM and as well as the control group, however this trend of change was same in both the groups and was not statistically significant when compared between the two group (GDM versus control). A negative correlation of FMD was found with BMI, and HBA1c, that was stronger in GDM group.

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Effects of aerobic exercise on vascular function in nondialysis chronic kidney disease: a randomized controlled trial

AJP Renal Physiology ◽

10.1152/ajprenal.00539.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. F898-F905 ◽

Cited By ~ 9

Author(s):

Danielle L. Kirkman ◽

Meghan G. Ramick ◽

Bryce J. Muth ◽

Joseph M. Stock ◽

Ryan T. Pohlig ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Randomized Controlled Trial ◽

Aerobic Exercise ◽

Vascular Function ◽

Controlled Trial ◽

Ringer Solution ◽

Microvascular Function ◽

Flow Mediated Dilation ◽

Randomized Controlled ◽

Artery Flow

Endothelial dysfunction and arterial stiffness are nontraditional risk factors of chronic kidney disease (CKD)-related cardiovascular disease (CVD) that could be targeted with exercise. This study investigated the effect of moderate to vigorous aerobic exercise on vascular function in nondialysis CKD. In this randomized, controlled trial, 36 nondialysis patients with CKD (means ± SE, age: 58 ± 2 yr, estimated glomerular filtration rate: 44 ± 2 ml·min−1·1.73 m−2) were allocated to an exercise training (EXT) or control (CON) arm. The EXT group performed 3 × 45 min of supervised exercise per week at 60–85% heart rate reserve for 12 wk, whereas the CON group received routine care. Outcomes were assessed at 0 and 12 wk. The primary outcome, microvascular function, was assessed via cutaneous vasodilation during local heating measured by laser-Doppler flowmetry coupled with microdialysis. Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution and 2) the superoxide scavenger tempol. Conduit artery function was assessed via brachial artery flow-mediated dilation. Aortic pressure waveforms and pulse wave velocity were acquired with tonometry and oscillometry. Microvascular function improved after EXT ( week 0 vs . week 12, EXT: 87 ± 2% vs. 91 ± 2% and CON: 86 ± 2% vs. 84 ± 3%, P = 0.03). At baseline, pharmacological delivery of tempol improved microvascular function (Ringer solution vs. tempol: 86 ± 1% vs. 90 ± 1%, P = 0.02) but was no longer effective after EXT (91 ± 2% vs. 87 ± 1%, P = 0.2), suggesting that an improved redox balance plays a role in EXT-related improvements. Brachial artery flow-mediated dilation was maintained after EXT (EXT: 2.6 ± 0.4% vs. 3.8 ± 0.8% and CON: 3.5 ± 0.6% vs. 2.3 ± 0.4%, P = 0.02). Central arterial hemodynamics and arterial stiffness were unchanged after EXT. Aerobic exercise improved microvascular function and maintained conduit artery function and should be considered as an adjunct therapy to reduce CVD risk in CKD.

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