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

Continuous passive leg movement (PLM) is a promising clinical assessment of the age-related decline in peripheral vascular function. To further refine PLM, this study evaluated the efficacy of a single PLM (sPLM), a simplified variant of the more established continuous movement approach, to delineate between healthy young and old men based on vascular function. Twelve young (26 ± 5 yr) and 12 old (70 ± 7 yr) subjects underwent sPLM (a single passive flexion and extension of the knee joint through 90°), with leg blood flow (LBF, common femoral artery with Doppler ultrasound), blood pressure (finger photoplethysmography), and leg vascular conductance (LVC) assessed. A receiver operator characteristic curve analysis was used to determine an age-specific cut score, and a factor analysis was performed to assess covariance. Baseline LBF and LVC were not different between groups ( P = 0.6). The high level of covariance and similar predictive value for all PLM-induced LBF and LVC responses indicates LBF, alone, can act as a surrogate variable in this paradigm. The peak sPLM-induced increase in LBF from baseline was attenuated in the old (Young: 717 ± 227, Old: 260 ± 97 ml/min, P < 0.001; cut score: 372 ml/min), as was the total LBF response (Young: 155 ± 67, Old: 26 ± 17 ml, P < 0.001; cut score: 58 ml). sPLM, a simplified version of PLM, exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction, as evidenced by an age-related attenuation in the peripheral hyperemic response and a clearly delineated age-specific cut score. NEW & NOTEWORTHY Single passive leg movement (sPLM) exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction. sPLM displayed an age-related reduction in the peripheral hemodynamic response for amplitude, duration, initial rate of change, and total change with clearly delineated age-specific cut scores. sPLM has a strong candidate variable that is a simple single numeric value, for which to appraise peripheral vascular function, the 45-s hyperemic response (leg blood flow area under the curve: 45 s).

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The role of the endothelium in the hyperemic response to passive leg movement: looking beyond nitric oxide

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00784.2020 ◽

2020 ◽

Author(s):

Joel D. Trinity ◽

Oh Sung Kwon ◽

Ryan M. Broxterman ◽

Jayson R. Gifford ◽

Andrew C. Kithas ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Vascular Function ◽

No Synthase ◽

Ketorolac Tromethamine ◽

Arterial Infusion ◽

Healthy Men ◽

Leg Movement ◽

Hyperemic Response

Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite NO synthase (NOS) inhibition. Therefore, in 9 young healthy men (25±4 yrs), this investigation aimed to determine if the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement) when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of NG-monomethyl L-arginine (L-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome P450 (CYP450) by L-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF (LBFAUC) response to both PLM (control: 456±194, L-NMMA: 168±127 ml, p<0.01) and sPLM (control: 185±171, L-NMMA: 62±31 ml, p=0.03). The combined inhibition of NOS, COX, and CYP450 (i.e. L-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBFAUC: 271±97 ml, p>0.05) or sPLM (LBFAUC: 72±45 ml, p>0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent, hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests.

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Perfusion pressure and movement-induced hyperemia: evidence of limited vascular function and vasodilatory reserve with age

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00656.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. H610-H619 ◽

Cited By ~ 22

Author(s):

H. Jonathan Groot ◽

Joel D. Trinity ◽

Gwenael Layec ◽

Matthew J. Rossman ◽

Stephen J. Ives ◽

...

Keyword(s):

Blood Flow ◽

Vascular Function ◽

Perfusion Pressure ◽

The Elderly ◽

Passive Movement ◽

Hemodynamic Responses ◽

Central Hemodynamic ◽

Seated Posture ◽

No Bioavailability ◽

The Impact

To better understand the mechanisms contributing to reduced blood flow with age, this study sought to elucidate the impact of altered femoral perfusion pressure (FPP) on movement-induced hyperemia. Passive leg movement was performed in 10 young (22 ± 1 yr) and 12 old (72 ± 2 yr) healthy men for 2 min, with and without a posture-induced change in FPP (∼7 ± 1 ΔmmHg). Second-by-second measurements of central and peripheral hemodynamic responses were acquired noninvasively (finger photoplethysmography and Doppler ultrasound, respectively), with FPP confirmed in a subset of four young and four old subjects with arterial and venous catheters. Central hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial pressure) were not affected by age or position. The young exhibited a ∼70% greater movement-induced peak change in leg blood flow (ΔLBFpeak) in the upright-seated posture (supine: 596±68 ml/min; upright: 1,026 ± 85 ml/min). However, in the old the posture change did not alter ΔLBFpeak (supine: 417±42 ml/min; upright: 412±56 ml/min), despite the similar increases in FPP. Similarly, movement-induced peak change in leg vascular conductance was ∼80% greater for the young in the upright-seated posture (supine: 7.1 ± 0.8 ml·min−1·mmHg−1; upright: 12.8 ± 1.3 ml·min−1·mmHg−1), while the old again exhibited no difference between postures (supine: 4.7 ± 0.4 ml·min−1·mmHg−1; upright: 4.8 ± 0.5 ml·min−1·mmHg−1). Thus this study reveals that, unlike the young, increased FPP does not elicit an increase in movement-induced hyperemia or vasodilation in the old. In light of recent evidence that the majority of the first minute of passive movement-induced hyperemia is predominantly nitric oxide (NO) dependent in the young, these findings in the elderly may be largely due to decreased NO bioavailability, but this remains to be definitively determined.

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Passive leg movement and nitric oxide-mediated vascular function: the impact of age

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00806.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. H672-H679 ◽

Cited By ~ 35

Author(s):

Joel D. Trinity ◽

H. Jonathan Groot ◽

Gwenael Layec ◽

Matthew J. Rossman ◽

Stephen J. Ives ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Function ◽

Area Under The Curve ◽

The Elderly ◽

Novel Approach ◽

Leg Movement ◽

The Impact ◽

Male Subjects ◽

Peak Increase

In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; l-NMMA: 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; l-NMMA: 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: −31 ± 18 ml) than the young (LBF: −129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

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Aerobic training status does not attenuate prolonged sitting-induced lower limb vascular dysfunction

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0420 ◽

2019 ◽

Vol 44 (4) ◽

pp. 425-433 ◽

Cited By ~ 5

Author(s):

Ryan S. Garten ◽

Austin C. Hogwood ◽

Jennifer B. Weggen ◽

R. Carson Fralin ◽

Kathryn LaRosa ◽

...

Keyword(s):

Blood Flow ◽

Lower Limb ◽

Vascular Function ◽

Aerobic Training ◽

Vascular Dysfunction ◽

Area Under The Curve ◽

Training Status ◽

Prolonged Sitting ◽

Leg Movement ◽

The Relationship

This study examined if the degree of aerobic training protects against the lower limb vascular dysfunction associated with a prolonged sitting bout. Ten young, aerobically trained (AT) and 10 young, untrained (UT) individuals completed a prolonged (3 h) sitting bout. Leg vascular function was measured prior to and at 1.5 and 3 h into the prolonged sitting bout using the passive leg movement (PLM) technique. PLM-induced hyperemia was significantly reduced from baseline at 1.5 and 3 h into the prolonged sitting bout in both groups when evaluated as peak change in leg blood flow from baseline (Δ LBF) (UT: 956 ± 140, 586 ± 80, and 599 ± 96 mL·min−1 at baseline, 1.5 h, and 3 h, respectively; AT: 955 ± 183, 789 ± 193, and 712 ± 131 mL·min−1 at baseline, 1.5 h, and 3 h, respectively) and LBF area under the curve (UT: 283 ± 73, 134 ± 31, and 164 ± 42 mL·min−1 at baseline, 1.5 h, and 3 h, respectively; AT: 336 ± 86, 242 ± 86, and 245 ± 73 mL·min−1 at baseline, 1.5 h, and 3 h, respectively), but no significant differences between groups were revealed. No significant correlations were observed when examining the relationship between maximal oxygen uptake (relative and absolute) and reductions in leg vascular function at 1.5 and 3 h into the prolonged sitting bout. This study revealed that aerobic training did not provide a protective effect against prolonged sitting-induced lower limb vascular dysfunction and further highlights the importance of reducing excessive sitting in all populations.

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Resistive exercise versus resistive vibration exercise to counteract vascular adaptations to bed rest

Journal of Applied Physiology ◽

10.1152/japplphysiol.00760.2009 ◽

2010 ◽

Vol 108 (1) ◽

pp. 28-33 ◽

Cited By ~ 20

Author(s):

Noortje T. L. van Duijnhoven ◽

Dick H. J. Thijssen ◽

Daniel J. Green ◽

Dieter Felsenberg ◽

Daniel L. Belavý ◽

...

Keyword(s):

Blood Flow ◽

Femoral Artery ◽

Superficial Femoral Artery ◽

Vascular Function ◽

Bed Rest ◽

Flow Mediated Dilation ◽

Resistive Exercise ◽

Vibration Exercise ◽

Echo Doppler Ultrasound ◽

The Impact

Bed rest results in marked vascular adaptations, and resistive vibration exercise (RVE) has been shown to be an effective countermeasure. As vibration exercise has practical and logistical limitations, the use of resistive exercise (RES) alone has the preference under specific circumstances. However, it is unknown if RES is sufficient to prevent vascular adaptations to bed rest. Therefore, the purpose of the present study was to examine the impact of RES and RVE on the vascular function and structure of the superficial femoral artery in young men exposed to 60 days of bed rest. Eighteen healthy men (age: 31 ± 8 yr) were assigned to bed rest and randomly allocated to control, RES, or RVE groups. Exercise was applied 3 times/wk for 5–7 min/session. Resting diameter, blood flow, flow-mediated dilation (FMD), and dilator capacity of the superficial femoral artery were measured using echo-Doppler ultrasound. Bed rest decreased superficial femoral artery diameter and dilator capacity ( P < 0.001), which were significantly attenuated in the RVE group ( P < 0.01 and P < 0.05, respectively) but not in the RES group ( P = 0.202 and P = 0.696, respectively). Bed rest significantly increased FMD ( P < 0.001), an effect that was abolished by RVE ( P < 0.005) but not RES ( P = 0.078). Resting and hyperemic blood flow did not change in any of the groups. Thus, RVE abolished the marked increase in FMD and decrease in baseline diameter and dilator capacity normally associated with prolonged bed rest. However, the stimulus provided by RES alone was insufficient to counteract the vascular adaptations to bed rest.

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Passive Leg Movement Technique for Assessing Vascular Function: Further Defining the Distribution of Blood Flow

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000562484.26816.19 ◽

2019 ◽

Vol 51 (Supplement) ◽

pp. 663-664

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

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Alpha adrenergic receptor regulation of blood flow during passive leg movement: The impact of age.

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.06548 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

D. Taylor La Salle ◽

James Cerbie ◽

Jeremy Alpenglow ◽

Catherine Jarret ◽

Jesse C. Craig ◽

...

Keyword(s):

Blood Flow ◽

Adrenergic Receptor ◽

Receptor Regulation ◽

Alpha Adrenergic Receptor ◽

Leg Movement ◽

The Impact

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Passive leg movement-induced vasodilation in women: the impact of age

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00422.2015 ◽

2015 ◽

Vol 309 (5) ◽

pp. H995-H1002 ◽

Cited By ~ 9

Author(s):

H. Jonathan Groot ◽

Matthew J. Rossman ◽

Joel D. Trinity ◽

Gwenael Layec ◽

Stephen J. Ives ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Function ◽

Heart Rate Response ◽

Perfusion Pressure ◽

Female Population ◽

Novel Method ◽

Seated Posture ◽

Leg Movement ◽

The Impact ◽

Hemodynamic Measurements

Passive leg movement (PLM), an assessment of predominantly nitric oxide-dependent vasodilation, is decreased with age and cannot be augmented by posture-induced increases in femoral perfusion pressure in older men. However, this novel method of assessing vascular function has yet to be used to evaluate alterations in nitric oxide-dependent vasodilation with age in females. PLM was performed in 10 young (20 ± 1 yr) and 10 old (73 ± 2 yr) women in both the supine and upright-seated postures, whereas central and peripheral hemodynamic measurements were acquired second by second using noninvasive techniques (finger photoplethysmography and Doppler ultrasound, respectively). The heart rate response to PLM was attenuated in the old compared with the young in both the supine (young, 10 ± 1; and old, 5 ± 1 beats/min; P < 0.05) and upright-seated posture (young, 10 ± 2; and old, 5 ± 1 beats/min; P < 0.05), leading to a blunted cardiac output response in the old in the upright-seated posture (young, 1.0 ± 0.2; and old, 0.3 ± 0.1 l/min; P < 0.05). The PLM-induced peak change in leg vascular conductance was lower in the old compared with the young in both postures (young supine, 5.7 ± 0.5; old supine, 2.6 ± 0.3; young upright, 9.2 ± 0.7; and old upright, 2.2 ± 0.4 ml·min−1·mmHg−1; P < 0.05) and was significantly augmented by the upright-seated posture in the young only, revealing a vasodilatory reserve capacity in the young (3.5 ± 0.6 ml·min−1·mmHg−1, P < 0.05) that was absent in the old (−0.5 ± 0.3 ml·min−1·mmHg−1, P = 0.18). These data support previous literature demonstrating attenuated PLM-induced vasodilation with age and extend these findings to include the female population, thus bolstering the utility of PLM as a novel assessment of vascular function across the life span in humans.

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