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A Case of Muscle Contraction-Induced Ischemic Limb Hyperemia in a Patient with Peripheral Arterial Disease during Incremental Repeat Isometric Knee Extensor Workloads



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World Journal of Cardiovascular Diseases, 2020, 10, 796-808
ISSN Online: 2164-5337
ISSN Print: 2164-5329
10.4236/wjcd.2020.1012076 Dec. 29, 2020 796
World Journal of Cardiovascular Diseases
A Case of Muscle Contraction-Induced Ischemic
Limb Hyperemia in a Patient with Peripheral
Arterial Disease during Incremental Repeat
Isometric Knee Extensor Workloads
Takuya Osada1,2
1Cardiac Rehabilitation Center, Tokyo Medical University Hospital, Tokyo, Japan
2Rehabilitation Center, Tokyo Medical University Hospital, Tokyo, Japan
To determine whether muscle contraction-
induced leg blood
flow (LBF) during exercise may be altered in a patient with an ischemic limb
due to peripheral arterial disease (PAD) compared with the non-
PAD limb.
Case Presentation:
A 66-year-old male patient wi
th intermittent claudication
due to PAD in the right leg (ankle brachial pressure index, 0.69) showed
complete obstruction in both common iliac arteries including internal/external
segments with collaterals above the femoral artery and popliteal artery wit
collaterals, and in the healthy left non-PAD-leg (1.06). He attempted unila-
teral repeat isometric knee extensions at a target contraction rhythm with
each leg at incremental contraction intensities (5%, 10%, and 30% of maxi-
mum voluntary contraction [MVC] for 3 min at each intensity). Blood veloc-
ity/flow (Doppler ultrasound) in the femoral artery, blood pressure, and leg
vascular conductance (LVC) were measured. Isometric thigh MVC strength
pre-exercise was similar between the PAD-leg (48.0 kg) and non-PAD-
(48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-
(316) and non-PAD-
leg (327). Blood pressure increases were similar during
exercise. Average exercising LBF in ml/min in the last 1 min at each intensity
was higher in the PAD-leg than the non-PAD-
leg: 1087 vs. 471 at 5%, 2097
vs. 712 at 10%, and 2656 vs. 1517 at 30% MVC with a close positive linear re-
lationship between LBF and %MVC in the non-PAD-leg (r = 0.999, P
< 0.01),
in agreement with previous findings, but less significant in the PAD-
leg (r =
0.879, P = NS), indicating intense vasodilation (increasing LVC) in the
PAD-leg compared with the non-PAD-leg.
Knee extensor exer-
cising LBF in the femoral artery was dissimilar between the PAD-
leg and
non-PAD-leg at the same exercise intensity, even though pre-exercising LBF
How to cite this paper:
Osada, T. (2020)
Case of Muscle Contraction
-Induced Ischem-
Limb Hyperemia in a Patient with Peri-
pheral Arterial Disease during Incr
Repeat Isometric Knee Extensor Wor
World Journal of Cardiovascular Di
, 796-808.
November 27, 2020
December 26, 2020
December 29, 2020
Copyright © 20
20 by author(s) and
Research Publishing Inc.
This work is licensed under the Creative
Commons Attribution International
(CC BY 4.0).
Open Access
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World Journal of Cardiovascular Diseases
was the same. Further research on the time-course in hemodynamics during
leg exercise in PAD might potentially provide insight for the cardiovascular
adjustment in severity of arteriosclerosis, stenosis and/or collaterals reserve.
Leg Blood Flow, Peripheral Arterial Disease, Collaterals Flow, Repeat
Isometric Knee Extensor Exercise, Doppler Ultrasound
1. Introduction
Peripheral arterial disease (PAD), resulting in intermittent claudication, is asso-
ciated with low exercise tolerance [1]. This can reduce levels of daily physical ac-
tivity (for example, low walking ability), lead to poor health, and impair quality
of life [2]. Long-term, habitual exercise improves walking distance with less pain
in the leg [3] [4]. This may potentially be due to alteration (or adjustment) of the
peripheral hemodynamics in the leg and/or improvement in the muscle oxida-
tive capacity or potential oxygen supply via developed collateral circulation by
exercise training [5]. Therefore, it might be important to understand the role of
the blood flow circulatory effect related to voluntary muscle contractions such as
knee and/or plantar exercise thorough hemodynamic imaging using real-time
recording with a non-invasive method.
In 1976, Nicolaides reported the ability of blood velocity tracing in the femor-
al artery to predict the state of the proximal aortoiliac segment in PAD. Fur-
thermore, an illustration of changes in femoral artery blood velocity after exer-
cise was described [6]. There have been numerous previous studies on the time
course of muscle contraction-induced blood flow hyperemia in the limb conduit
artery due to exercise in healthy subjects [7], but less acknowledgement of the
reference values for exercising blood flow in the leg conduit artery with lesion of
vascular disease.
Recent advances in ultrasonography with two-dimensional anatomical imag-
ing of monitored pulse flow and Doppler waveform can precisely evaluate ar-
terial lesions. Thus, the measurement of (changes in) blood velocity profile can
provide valuable information on the severity of stenosis due to arteriosclerosis as
well as existence of collaterals induced by ischemia with obstruction of artery
flow and to evaluate alterations in the magnitude of peak systolic blood velocity
and/or diastolic blood velocity profile in a basal non-exercising state in PAD [8].
In addition, Doppler imaging can provide high temporal resolution of blood
velocity in a conduit artery at rest. Moreover, rapid changes in blood velocity in
a conduit artery located in a gap into a major muscle group can also be detected
with muscle contraction and relaxation and/or cardiac beat-by-beat during exer-
cise, muscle contraction frequency and workload, and in relation to vasodilata-
tion/vasoconstriction [9] [10] [11] [12]. In previous studies in healthy legs on
exercise leg blood flow (LBF), there were positive linear correlations between
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unilateral LBF and workload during steady state dynamic leg exercise with a va-
lidated operator technique [13] [14] [15] [16].
Limited information is available on whether the muscle contraction-induced
ischemic limb flow response in PAD may be altered during leg exercise. Thus, in
the present case with PAD, we sought to determine the magnitude of thigh mus-
cle strength-dependent blood flow in the femoral artery located above an arteri-
osclerotic lesion using Doppler ultrasound.
2. Case Presentation
A male (66 yr 3 mo, 173.8 cm, 69.5 kg) had been diagnosed 5 years previously
with hypertension and PAD in the right leg with intermittent claudication (Fon-
taine classification II). The intermittent claudication had appeared 2 years prior
to the study. In the patients right leg there was a region of complete obstruction
due to arteriosclerosis in the right common iliac artery, including the inter-
nal-external iliac artery and the developed collaterals above the common femoral
artery as well as complete obstruction of the popliteal artery with collaterals, as
determined by angiography, and the patients left leg was healthy and without
PAD. Ankle brachial pressure index (ABI) was 0.69 for the PAD-leg and 1.06 for
the non-PAD-leg (CAVIpluse VaSera VS-1000, Fukuda Denshi, Tokyo, Japan).
A normal ABI is defined as a resting measurement greater than 0.9. Any value of
0.9 or less indicates the presence of PAD, with lower ABI values indicating more
severe PAD. Patients with ABI values of 0.70 to 0.90 may be asymptomatic or
have very mild symptoms of intermittent claudication [17].
The patient had been taking oral cilostazol, an antiplatelet agent with vasodi-
latory properties, and valsartan, as an antihypertensive agent. He has continued
hospital-based rehabilitation with 30-min aerobic bicycle ergometer exercise ap-
proximately 2 times per week for 2 years 3 months. Cardiopulmonary ergometer
exercise tests indicated a maximum oxygen consumption of 21.69 ml/kg/min
(6.2 Mets), with a maximum workload as 121 watts and maximum heart rate of
141 beat per minute. The present trial was conducted according to the principles
of the Declaration of Helsinki (1964) and with approval (approval No. 958) of
the Institutional Ethics Committee of our institution. The patient gave written
consent and was informed of the nature and purpose of the study, as well as po-
tential risks and discomfort. The patient also understood that they could with-
draw from the study at any time without consequence.
3. Protocol
3.1. Exercise Model
The patient performed incremental unilateral (one-legged) isometric knee exten-
sor exercise in a sitting position, which is an appropriate model for the determina-
tion of comprehensive LBF in the femoral artery during limb muscle contractions
(Figure 1). This exercise model allows stable measurements of femoral arterial
blood velocity using Doppler ultrasound, whereas usual walking/running models
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Figure 1. One-legged knee extensor exercise model. Repeat isometric muscle contraction
performed as 5-s voluntary (active) isometric knee muscle contraction and 5-s muscle re-
laxation pause (10 s/duty cycle) for 3 min at 5%, 10%, 30%, and 50% MVC. The knee ex-
tensor contraction rhythm was maintained by following the pace of a visible and audible
metronome. The knee extensor contraction strength (target intensity) was performed by
visualizing the contraction strength displayed in real time on a force monitor. Simulta-
neous recording of hemodynamic parameters was measured for the whole experiment.
do not easily allow LBF measurement in the leg conduit artery, due to the diffi-
culty of fixing the scanning probe to the hip joint [16] [18] [19] [20]. The patient
performed exercise with the hips at a 100˚ angle, the thigh positioned horizon-
tally with the knee joint bent at an approximately 110˚ angle, and their foot and
ankle secured to upper and lower rods with the use of a custom-designed Mei-
ko-100 knee-extension ergometer (Meiko Co. Ltd., Tokyo, Japan) [13].
3.2. Exercise Intensity and Muscle Contraction-Relaxation
Prior to exercise, the maximum voluntary contraction force (MVC) expressed as
the maximum muscle strength throughout a single muscle contraction bout in
each leg was measured using a knee-extension ergometer connected to a
strain-gauge (Meiko Co. Ltd. ST-200, Tokyo, Japan). The MVC was determined by
the averaging over five repetitions for a bolus of MVC. The target intensity at iso-
metric muscle contraction phase increased every 3 min corresponding to 5%, 10%,
30%, and 50% MVC. The recovery phase lasted 10 min (Figure 2). A duty cycle
for muscle contractionrelaxation was at a rate of 5-s isometric knee extensor con-
tractions at the target exercise intensity and consequently 5-s muscle relaxation
(pause) corresponding to a cycle of 10 s (6 cycles per minutes) with recording of
the muscle strength curve. The patient attempted to maintain the target intensity
using a digital visualization of the intensity displayed in real time on a monitor.
The duration of muscle contraction and muscle rhythm followed the pace of an
audible metronome (Quartz Metronome SQ 70, SEIKO, Tokyo Japan). The pa-
tient performed the exercise until they reached all-out exhaustion with leg fatigue.
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Figure 2. Exercise protocol. The maximum voluntary contraction (MVC) strength was
measured for each leg at pre-exercise. There were four different target exercise intensities
in the multi-stage incremental unilateral isometric knee extensor exercise sessions, 5%,
10%, 30%, and 50% of MVC, and each target intensity for 3 min. A 10-min recovery was
taken after the end of exercise. The participant attempted to exercise to exhaustion with
leg fatigue.
3.3. Blood Velocity and Vessel Diameter in the Femoral Artery
An ultrasonograph (SONOS 1500, ultrasound imaging system, HP 77035A,
Hewlett Packard, Tokyo Japan) with a 2-dimensional ultrasonic imager and a
pulse Doppler flowmeter using linear array prove (7.5 MHz) was used. Mea-
surement in the proximal femoral artery was at a site with minimum turbulence
and without influence of the inguinal region on hemodynamics above the bifur-
cation, thereby enabling easy and reliable measurement during leg exercise [10]
[11] [12] [13]. In the present patient, there was no pathology (severe stenosis or
collateral vessel) in the target femoral artery (sampling point) monitoring arteri-
al pulsation color images above the bifurcation into the superficial and profunda
femoral branch (see 2-D image for PAD in Figure 3). Validated blood velocity
measurement in the femoral artery has been reported previously during repeated
muscle contractions using Doppler ultrasound [9] [10] [11].
Prior to exercise, the vessel diameter at pre-exercise (basal state) was meas-
ured only for determination of the cross-sectional area. The systolic and diastolic
vessel diameters were also measured under perpendicular insonation and calcu-
lated in relation to the temporal duration of the ECC recording curve as [(sys-
tolic vessel diameter × 1
3) + (diastolic vessel diameter × 2
3)] [9] [10] [11]. LBF
was calculated by multiplying the cross-sectional area [area =
× (vessel diame-
2)2] by mean blood velocity.
3.4. Blood Pressure, Heart Rate and Leg Vascular Conductance
Blood pressure was monitored continuously using an auricular plethysmogra-
phy device with oscillometric calibration, with a cuff tourniquet placed on the
upper arm (RadiaPress RBP-100, KANDS, Aichi, Japan) with data stored using a
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Figure 3. Comparison in blood velocity profile in femoral artery between PAD and non-PAD. The blood velocity in the femoral
artery above the bifurcation monitored in B-mode was clearly different between the PAD-leg (a monophasic pattern with low
resistance component) and the non-PAD-leg (normal triphasic pattern) at pre-exercise in the left panel. The upper panels are for
the PAD-leg and the lower panels for the non-PAD-leg. The blood velocity profile showed the restricted blood flow due to in-
creases in intramuscular pressure during muscle contraction (→), and hyperemic increasing blood flow during muscle relaxation
(←). Marked higher blood velocity in the diastolic component was obviously seen in the PAD-leg than the non-PAD-leg at
30%MVC in the middle panel (note the higher scale on the vertical axis in the PAD-leg compared with the non-PAD-leg). The
magnitude of the hyperemic state after the end of exercise was enhanced in the PAD-leg compared with the non-PAD-leg in the
right panel. PAD: peripheral arterial disease, %MVC: percentage of maximum voluntary contraction.
PowerLab data acquisition system (Chart v.4.2.3 software; AD Instruments,
Sydney, Australia). Heart rate was measured using the beat-by-beat from conti-
nuous recording of the blood pressure wave. Leg vascular conductance was cal-
culated as LBF divided by blood pressure (LBF/blood pressure) using the unit
3.5. Sampling Collections and Evaluations
We collected the samples for hemodynamic measures at pre-exercise and during
exercise (every 5-s muscle contraction phase, every 5-s muscle relaxation phase,
and every 10-s muscle contractionrelaxation duty cycle) and recovery (imme-
diately at the end of the exercise point, and every 1 min). Furthermore, the av-
erage LBF value during steady state exercise was also determined as a mean val-
ue (6th duty muscle contractionrelaxation cycles) in the last 1 min of exercise at
each exercise intensity. Statistical comparisons were examined using a linear fit-
ting regression correlation coefficient (r), and P-value were conducted between
mean LBF and the mean muscle contraction strength (relative value as %MVC)
in the last 1 min of exercise at each exercise intensity (Microsoft 365 Excel). A
P-value < 0.05 was considered significant.
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4. Results
ABI was lower in the ischemic PAD-leg (0.69) than the healthy non-PAD-leg
(1.06), which may indicate the existence of stenosis and/or obstruction in the limb
artery below 0.9. The MVC in one-legged isometric knee extensor muscle contrac-
tion was similar between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg), which
indicated the same relative target muscle contraction intensity (%MVC). The
pre-exercise LBF in a basal resting state was similar between 316 ml/min in the
PAD-leg and 327 ml/min in the non-PAD-leg. In the PAD-leg in a pre-exercise
basal state there was a monophasic blood velocity profile, but a triphasic blood ve-
locity pattern was seen in the non-PAD-leg (Figure 3). The duration of unilateral
leg exercise for achieving to exhaustion (leg fatigue but not intermittent claudica-
tion) was shorter in the PAD-leg at 10 min than the non-PAD-leg at 11 min 40 sec
and it was not to possible to accomplish the whole session at 50% MVC.
The magnitude of the average LBF was higher in the PAD-leg than the
non-PAD-leg during exercise (Figure 4). The average exercise LBF in ml/min in
the last 1 min of each exercise intensity was higher in the PAD-leg than the
non-PAD-leg: 1087 vs 471 at 5% MVC, 2097 vs 712 at 10% MVC, and 2656 vs
1517 at 30% MVC in Figure 4A, which may indicate excess vasodilation (in-
creasing LVC) in the PAD-leg compared with the non-PAD-leg in Figure 4B.
The increase in blood pressure was similar in the PAD-leg and non-PAD-leg
during exercise (Figure 4C). The increase in heart rate was similar between the
PAD-leg and non-PAD-leg in Figure 4D, which can be used to validate the phy-
siological response using the same muscle contraction strength (Figure 4E).
The LBF in both legs increased in a manner almost dependent on muscle con-
traction intensity, furthermore the non-PAD-leg showed that the increase in
LBF was statistically significant (r = 0.999, P< 0.01) with positive linearity
by %MVC, but not in the PAD-leg (r = 0.879, P = NS) (Figure 5).
5. Discussion
The present trial may provide unique insights on patients with PAD that patho-
physiologically have a limitation in perfusion blood flow to skeletal muscles in
the periphery, although this result is only for one patient without consideration
of the reserve capacity in the vasculature (oxygen delivery compensated by col-
lateral flow, etc.) following long-term morbidity with impairment of the blood
flow pathway between upstream and downstream and/or other interventions
such as medication effectiveness or exercise therapy (changes in exercise toler-
ance and/or muscle strength).
5.1. Muscle Contraction-Induced Hyperemia in PAD and Non-PAD
Impairment from stenosis and atherosclerosis due to an obstructed conduit ar-
tery in PAD should functionally be a limitation in perfusion flow via the muscle
capillary, and there have been recent report evaluating the microcirculation using
contrast-enhanced ultrasound [21] [22] [23] and oxygenation using near-infrared
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Figure 4. Time-course of hemodynamics parameter at rest, during exercise, and recovery. The time-course in LBF (A) as well as
LVC (B) was higher in the PAD-leg (red line) than the non-PAD-leg (black line). The oscillation in LBF indicated restricted flow
during muscle contraction (below circles) and non-restricted flow during muscle relaxation (above circles). Average value of mus-
cle contraction and relaxation in a duty cycle appeared rectangular in the PAD-leg (blue color) and the non-PAD-leg (green color).
Average value of blood pressure (C) and heart rate (D) determined by muscle contraction and relaxation in a duty cycle during
exercise were similar between the PAD-leg and non-PAD-leg. In both the PAD-leg and the non-PAD-leg, the muscle strength
corresponding to target intensity as relative muscle strength (%MVC) was stable in each voluntary isometric muscle contraction
(E). Muscle strength during muscle relaxation was not plotted because the value was zero. Muscle strength was almost same at
each contraction intensity (%MVC) because of similarity in MVC between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg).
Average LBF during last 1 min of steady state exercise () was used for the relationship with %MVC in Figure 5. LBF: leg blood
flow, LVC: leg vascular conductance, PAD: peripheral arterial disease, %MVC: percentage of maximum voluntary contraction.
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Figure 5. Relationship between LBF and %MVC during exercise. There was a statistically
significant (r = 0.999, P < 0.01 in black solid line) positive linear relationship between
LBF and %MVC in the non-PAD-leg despite fewer sample, but no significance in the
PAD-leg (r = 0.879, P = NS in dashed red line). The LBF at 50% MVC was not included
because the whole exercise secession was not completed. LBF: leg blood flow, %MVC:
percentage of maximum voluntary contraction, PAD: peripheral arterial disease.
spectroscopy [24] in the lower limb muscles during exercise. These studies in-
vestigated the relationship between muscle metabolism and perfusion flow in the
vascular bed because PAD is associated with severe exercise intolerance related
to impaired endothelial function and/or alterations in skeletal muscle phenotype
rather than hemodynamic impairment in the conduit artery.
On the other hand, during exercise the magnitude of hemodynamics in the leg
conduit artery from the upper stream around the lesion segment in PAD may
speculatively detect any physiological changes due to remodeling of the peri-
pheral circulation via development of significant collaterals with a change in
chronic ischemic state over time.
In fact there have been few previous reports to evaluate the time-course of ex-
ercising LBF in a conduit artery coordinated using precise repeat voluntary
muscle contraction strength (every muscle contraction-relaxation duty cycle)
even if the flow profile in the sampling area might be directly influenced by the
collaterals surrounding the obstructive lesion connected to the upper stream
and/or downstream during exercise. Possible reasons for the paucity of reports
are that it may not be easy to quantify and/or quality the role of comprehensive
blood flow supply via the development of collaterals from the upper stream
above the lesion to downstream with an intervention such as exercise therapy,
medication, and/or the collateral development in a cohort study.
The spectrum of lesions in the leg arteries in PAD with claudication is varied.
A long segmental obstruction can coexist with almost normal arterial segments
[8]. Thus, it was acceptable that the present patient also had a lesion in the right
common iliac artery including the internal-external iliac artery and the devel-
oped collaterals above the common femoral artery as well as complete obstruc-
tion of the popliteal artery with collaterals, whereas almost normal arteries in the
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left leg showed a normal ABI range.
In a present case with the above-mentioned PAD affecting a unilateral leg,
there was a clear difference in exercise LBF during incremental repeat isometric
knee extension between the PAD-leg and non-PAD-leg despite LBF in the basal
pre-exercise state being similar (Figure 4). The mechanism of muscle contrac-
tion-induced hyperemia in the PAD-leg compared with the non-PAD-leg shown
in a present case was naturally unclear in the cross-sectional analysis.
The present characteristics in both leg hemodynamics might be acceptable
because of the statistically significant (P< 0.01, n = 3) relationship between LBF
and %MVC as non-PAD leg in Figure 5 in agreement with our previous finding
in healthy participants [11] [12]. Moreover, accurate performance of each leg
exercise at the precise target contraction intensities (almost same MVC both leg)
may give credible data with a uniform oscillation in LBF value influenced by the
fluctuation in each muscle contraction strength (Figure 4E). Furthermore, dur-
ing exercise the physiological cardiovascular response both blood pressure and
heart rate was almost similar between the PAD-leg and non-PAD-leg (Figure 4C
and Figure 4D).
Exercise hyperemia with vasodilation is related to intrinsic (endothelial-related
factors, autacoid substances, metabolite and myogenic response) as well as extrin-
sic (autonomic nerve regulation, signal/reflexes with central command and exer-
cise pressor reflexes with mechanical muscle contraction/accumulated metabolite
product) regulation, as well as changes in arteriovenous pressure gradient due to
the mechanical muscle pump.
Thus, the promoted hyperemic state in the present PAD case can speculatively
be expressed as vessel dilation in the vascular bed due to multiple above-mentioned
factors enhanced by collaterals, medication control (vasodilatory properties in
disease leg), and/or long term of habitual exercise training [17].
5.2. Changes in Doppler Waveform during Exercise
PAD is often diagnosed by noting a change in the blood velocity pattern (wave-
forms) on the Doppler spectrum sampled above or distal to the site of an arterial
lesion. The artery blood velocity profile in a proximal region may appear nor-
mal; however, the downstream blood velocity profile will typically show a mo-
nophasic pattern, with a low resistance component if there is sufficient vasodila-
tion. Moreover, the monophasic pattern showed low-systolic forward flow ve-
locities persists during the cardiac cycle [8].
Furthermore, significant hemodynamics in the arterial lesion cause a period of
early diastolic flow reversal (backward negative flow) to decrease and ultimately
disappear as the lesion becomes more severe; consecutively the late diastolic
component of the forward flow increases in magnitude as the severity of the
proximal lesion worsens [8].
In Figure 3 at pre-exercise, the blood velocity profile in the present PAD pa-
tient was in agreement with such alterations in waveform, which is a loss of
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backward flow at the second dicrotic notch as well as slight increase in forward
flow at the end-diastolic phase. In addition, the peak systolic blood velocity was
lower in the PAD-leg (approximately 40 cm/s) than the non-PAD-leg (approx-
imately 60 cm/s).
These changes may represent a combination of factors such as progressive di-
latation and recruitment of peripheral arterioles within the distal vascular bed of
the leg as well as the development of many small collateral branches, which cor-
respond to the surrounding popliteal artery in the present patient.
During repeat isometric muscle contraction exercise, the peak systolic blood
velocity increased in both the PAD-leg and the non-PAD-leg, although a re-
stricted blood velocity profile was shown due to high intramuscular pressure
without changes in blood velocity in the diastolic phase. Conversely, the blood
velocity profile increased dramatically in both systolic and diastolic components
during muscle relaxation with strong vasodilation in the entire diastolic compo-
nent in both the PAD-leg and non-PAD-leg (see 30% MVC in Figure 3). The
higher blood velocity profile in the entire cardiac cycle was notably detected in
the PAD-leg than the non-PAD-leg. The post exercise hyperemic state after the
end of exercise, the blood velocity declined as exponential decay during recovery
in Figure 4A.
Doppler ultrasound can non-invasively detect with beat-to-beat high resolu-
tion the temporal pulsatile blood velocity profiles in the conduit artery at rest as
well as during muscle contractions for a patient with PAD.
6. Conclusion
This is an initial case trial in PAD for the determination of a time-course in LBF
in the femoral artery with surrounding collaterals during voluntary thigh muscle
contractions with knee extensor exercise using Doppler ultrasound. To investi-
gate rapid changes in exercise LBF in the conduit artery with the obstructive le-
sion in the vasculature above and/or below may be a new insight for considera-
tion of cardiovascular remodeling as a collateral flow with hyperemic state due
to transient exercise and/or possible effectiveness due to hospital-based rehabili-
tation. Further research on the peripheral circulatory response due to exercise is
necessary in PAD.
The author acknowledges the support of the late professor emeritus Atsuko Ka-
gaya of Japan Womens College of Physical Education, the late professor emeri-
tus Bengt Saltin of the CMRC and the late professor emeritus Hisao Iwane for-
merly of The Tokyo Medical College for contributions leading to the present
state of clinical physiology for rehabilitation. This study was supported in part
by the Academic FrontierProject for Private Universities (JWCPE), 2004-2008,
and a Grant-in-Aid for Scientific Research (C) in Scientific Research (No.
19500617) from the MEXT in Japan and the JSPS, 2007-2008 (to T. Osada).
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Conflicts of Interest
The author declares no conflicts of interest regarding the publication of this pa-
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Full-text available
Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. While leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole-leg blood flow and calf muscle microvascular perfusion following cuff occlusion and submaximal leg exercise between PAD patients (n=12, 69{plus minus}9 years) and healthy age-matched control participants (n=12, 68{plus minus}7 years). Microvascular blood flow (microvascular volume x flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: 1) 5 min of thigh-cuff occlusion; and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400N) using real-time contrast-enhanced ultrasound (CEU). Whole-leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Post-occlusion whole-leg blood flow and calf muscle microvascular perfusion were lower in PAD patients than controls, and these parameters were strongly correlated (r=0.84; p<0.01). During submaximal exercise, total whole-leg blood flow and vascular conductance were not different between groups. There were also no group differences in post-exercise calf muscle microvascular perfusion, although microvascular blood volume was higher in PAD patients than control (12.41±6.98 vs 6.34±4.98 aU; p=0.03). This study demonstrates that the impaired muscle perfusion of PAD patients during post-occlusion hyperemia is strongly correlated with disease severity, and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in PAD patients, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise.
Full-text available
Given recent technological developments, ultrasound Doppler can provide valuable measurements of blood velocity/flow in the conduit artery with high temporal resolution. In human-applied science such as exercise physiology, hemodynamic measurements in the conduit artery is commonly performed by blood flow feeding the exercising muscle, as the increase in oxygen uptake (calculated as a product of arterial blood flow to the exercising limb and the arterio-venous oxygen difference) is directly proportional to the work performed. The increased oxygen demand with physical activity is met through a central mechanism, an increase in cardiac output and blood pressure, as well as a peripheral mechanism, an increase in vascular conductance and oxygen extraction (a major part of the whole exercising muscles) from the blood. The increase in exercising muscle blood flow in relation to the target workload (quantitative response) may be one indicator in circulatory adjustment for the activity of muscle metabolism. Therefore, the determination of local blood flow dynamics (potential oxygen supply) feeding repeated (rhythmic) muscle contractions can contribute to the understanding of the factors limiting work capacity including, for instance, muscle metabolism, substance utilization and magnitude of vasodilatation in the exercising muscle. Using non-invasive measures of pulsed Doppler ultrasound, the validity of blood velocity/flow in the forearm or lower limb conduit artery feeding to the muscle has been previously demonstrated during rhythmic muscle exercise. For the evaluation of exercising blood flow, not only muscle contraction induced internal physiological variability, or fluctuations in the magnitude of blood velocity due to spontaneous muscle contraction and relaxation induced changes in force curve intensity, superimposed in cardiac beat-by-beat, but also the alterations in the blood velocity (external variability) due to a temporary sudden change in the achieved workload, compared to the target workload, should be considered. Furthermore, a small amount of inconsistency in the voluntary muscle contraction force at each kick seems to be unavoidable, and may influence exercising muscle blood flow, although subjects attempt to perform precisely similar repeated voluntary muscle contractions at target workload (muscle contraction force). This review presents the methodological considerations for the variability of exercising blood velocity/flow in the limb conduit artery during dynamic leg exercise assessed by pulsed Doppler ultrasound in relation to data previously reported in original research.
Full-text available
Context Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice.Objective To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics.Design and Setting The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the United States in June-October 1999.Patients A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Cardiovascular disease (CVD) was defined as a history of atherosclerotic coronary, cerebral, or abdominal aortic aneurysmal disease.Main Outcome Measures Frequency of detection of PAD; physician and patient awareness of PAD diagnosis; treatment intensity in PAD patients compared with treatment of other forms of CVD and with patients without clinical evidence of atherosclerosis.Results PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group). There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%) with PAD and CVD who were newly diagnosed during the survey. Eighty-three percent of patients with prior PAD were aware of their diagnosis, but only 49% of physicians were aware of this diagnosis. Among patients with PAD, classic claudication was distinctly uncommon (11%). Patients with PAD had similar atherosclerosis risk factor profiles compared with those who had CVD. Smoking behavior was more frequently treated in patients with new (53%) and prior PAD (51%) only than in those with CVD only (35%; P <.001). Hypertension was treated less frequently in new (84%) and prior PAD (88%) only vs CVD only (95%; P <.001) and hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%) only vs CVD only (73%, P<.001). Antiplatelet medications were prescribed less often in patients with new (33%) and prior PAD (54%) only vs CVD only (71%, P<.001). Treatment intensity for diabetes and use of hormone replacement therapy in women were similar across all groups.Conclusions Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. A simple ABI measurement identified a large number of patients with previously unrecognized PAD. Atherosclerosis risk factors were very prevalent in PAD patients, but these patients received less intensive treatment for lipid disorders and hypertension and were prescribed antiplatelet therapy less frequently than were patients with CVD. These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD. Figures in this Article Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome that affects approximately 8 to 12 million individuals in the United States and is associated with significant morbidity and mortality.1- 4 Because of its high prevalence, high rates of nonfatal cardiovascular ischemic events (myocardial infarction [MI], stroke, and other thromboembolic events), increased mortality, and diminution of quality of life, the consequences of PAD in US communities are significant.1- 5 A regional pilot study of community screening for PAD demonstrated that patient awareness of the PAD diagnosis was low and associated with low atherosclerosis risk factor, antiplatelet, and claudication treatment intensity.5 There have been no national efforts in the United States to detect PAD in community-based office practice, to assess both physician and patient awareness of the diagnosis, or to assess the intensity of medical treatments. PAD has not emerged as a focus of public health efforts to improve quality of life nor to decrease the associated cardiovascular ischemic risk. The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program was designed as a national investigation to assess the feasibility of detecting PAD using the ankle-brachial index (ABI) in office-based practices. Additional goals were to assess both patient and physician awareness of PAD, to evaluate the magnitude of the associated atherosclerosis risk factor burden, and to assess the intensity of use of risk-reduction strategies in community practice. The program evaluated the following hypotheses: (1) that PAD is prevalent but underdiagnosed in primary care practices and (2) that PAD is undertreated in terms of risk factor modification and use of antiplatelet therapies compared with that in other cardiovascular diseases (CVDs).
We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared spectroscopy (FD-NIRS), to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients (n=64) were randomly assigned to exercise and control groups. Patients in the exercise group received three months of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at three months in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29%(13%,50%) and 8%(1%,12%), respectively (p<0.001; median (25th percentile, 75th percentile)). These improvements across the exercise group population were significantly higher than corresponding changes in the control group (p<0.004). Exercise training also increased PWT by 49% (18%, 101%), (p = 0.01). However, within statistical error, the ABI, the resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin/myoglobin desaturation following cessation of maximal exercise, were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT.
This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans. Copyright © 2015 the American Physiological Society.
We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle microvascular perfusion in health and disease. Response to a post-occlusive reactive hyperaemia test was repeated on two occasions >48 h apart in healthy young (28 ± 7 y) and elderly controls (70 ± 5 y), and in peripheral arterial disease patients (PAD, 69 ± 7 y; n = 10, 9 and 8 respectively). Overall, within-individual reliability was poor (coefficient of variation [CV] range: 15–87%); the most reliable parameter was time to peak (TTP, 15–48% CV). Nevertheless, TTP was twice as long in elderly controls and PAD compared to young (19.3 ± 10.4 and 22.0 ± 8.6 vs. 8.9 ± 6.2 s respectively; p < 0.01), and area under the curve for contrast intensity post-occlusion (a reflection of blood volume) was ∼50% lower in elderly controls (p < 0.01 versus PAD and young). Thus, CEUS assessment of muscle perfusion during reactive hyperaemia demonstrated poor reliability, yet still distinguished differences between PAD patients, elderly and young controls.
Limb femoral arterial blood flow (LBF) is known to increase linearly with increasing workload under steady-state conditions, suggesting a close link between LBF and metabolic activity. We, however, hypothesized that sudden physiological and spontaneous changes in exercise rhythm, and consequently workload temporarily alter blood flow to the working muscle. LBF and its relation to fluctuations in the contraction rhythm and workload were therefore investigated. LBF, measured by Doppler ultrasound, and the achieved workload, were continuously measured in nine subjects, aiming to perform steady-state, one-legged, dynamic knee-extensor exercise at 30 and 60 contractions per minute (cpm), at incremental target workloads of 10, 20, 30 and 40 W. In agreement with previous findings, LBF increased positively and linearly (P<0.05) with increasing target workload. However, LBF was inversely and linearly related (P<0.05) to the actually achieved workload, when measured over 60 consecutive contraction-relaxation cycle bouts, for each target intensity at 30 and 60 cpm respectively. Thus any sudden spontaneous increase or decrease in the achieved workload transiently altered the relationship between LBF and the achieved workload. The influence upon the magnitude of LBF, due to fluctuations in the achieved workload from the target workload, was furthermore similar between target workload sessions at 30 and 60 cpm respectively. LBF was, however, not associated with variations in the contraction frequencies. These findings indicate that a transient sudden increase in the workload more rapidly impedes LBF and that vasodilatation may be elicited to restore the intensity related steady-state LBF response in relation to the average metabolic activity.