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World Journal of Cardiovascular Diseases, 2020, 10, 796-808
https://www.scirp.org/journal/wjcd
ISSN Online: 2164-5337
ISSN Print: 2164-5329
DOI:
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
Abstract
Background:
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
h
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-
leg
(48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-
leg
(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.
Conclusion:
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)
A
Case of Muscle Contraction
-Induced Ischem-
ic
Limb Hyperemia in a Patient with Peri-
pheral Arterial Disease during Incr
e
mental
Repeat Isometric Knee Extensor Wor
k-
loads
.
World Journal of Cardiovascular Di
s-
eases
,
10
, 796-808.
https://doi.org/10.4236/wjcd.20
20.1012076
Received:
November 27, 2020
Accepted:
December 26, 2020
Published:
December 29, 2020
Copyright © 20
20 by author(s) and
Scientific
Research Publishing Inc.
This work is licensed under the Creative
Commons Attribution International
License
(CC BY 4.0).
http://creativecommons.org/licenses/by/4.0/
Open Access
T. Osada
DOI:
10.4236/wjcd.2020.1012076 797
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.
Keywords
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 patient’s 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 patient’s 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
Frequency
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 contraction–relaxation 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 =
π
× (vessel diame-
ter
/
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
ml/min/mmHg.
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 contraction–relaxation 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 contraction–relaxation 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.
Acknowledgements
The author acknowledges the support of the late professor emeritus Atsuko Ka-
gaya of Japan Women’s 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 Frontier” Project 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-
per.
References
[1] Askew, C.D., Green, S., Walker, P.J., Kerr, G.K., Green, A.A., Williams, A.D. and
Febbraio, M.A. (2005) Skeletal Muscle Phenotype Is Associated with Exercise To-
lerance in Patients with Peripheral Arterial Disease.
Journal
of
Vascular
Surgery
, 41,
802-807. https://doi.org/10.1016/j.jvs.2005.01.037
[2] Hiatt, W.R. (2001) Medical Treatment of Peripheral Arterial Disease and Claudica-
tion.
New
England
Journal
of
Medicine
, 344, 1608-1621.
https://doi.org/10.1056/NEJM200105243442108
[3] Hiatt, W.R., Regensteiner, J.G., Hargarten, M.E., Wolfel, E.E. and Brass, E.P. (1990)
Benefit of Exercise Conditioning for Patients with Peripheral Vascular Disease.
Circulation
, 81, 602-609. https://doi.org/10.1161/01.CIR.81.2.602
[4] Larsen, O.A. and Lassen N.A. (1966) Effect of Daily Muscular Exercise in Patients
with Intermittent Claudication.
The
Lancet
, 288, 1093-1096.
https://doi.org/10.1016/S0140-6736(66)92191-X
[5] Stewart, K.J., Hiatt, W.R., Regensteiner, J.G. and Hirsch, A.T. (2002) Exercise
Training for Claudication.
New
England
Journal
of
Medicine
, 347, 1941-1951.
https://doi.org/10.1056/NEJMra021135
[6] Nicolaides, A.N., Gordon-Smith, L.C., Dayandas, J. and Eastcott, H.H.G. (1976) The
Value of Doppler Blood Velocity Tracings in the Detection of Aortoiliac Disease in
Patients with Intermittent Claudication.
Surgery
, 80, 774-778.
[7] Joyner, M.J. and Casey, D.P. (2015) Regulation of Increased Blood Flow (Hyper-
emia) to Muscles during Exercise: A Hierarchy of Competing Physiological Needs.
Physiological
Review
, 95, 549-601. https://doi.org/10.1152/physrev.00035.2013
[8] Polak, J.F. (2004) Peripheral Vascular Sonography. A Practical Guide. Second
Edition, Lippincott Williams & Wilkins, Philadelpha.
[9] Rådegran, G. (1997) Ultrasound Doppler Estimates of Femoral Artery Blood Flow
during Dynamic Knee Extensor Exercise in Humans.
Journal
of
Applied
Physiolo-
gy
, 83, 1383-1388. https://doi.org/10.1152/jappl.1997.83.4.1383
[10] Osada, T. (2004) Muscle Contraction-Induced Limb Blood Flow Variability during
Dynamic Knee Extensor.
Medicine
&
Science
in
Sports
&
Exercise
, 36, 1149-1158.
https://doi.org/10.1249/01.MSS.0000132272.36832.6A
[11] Osada, T. and Rådegran, G. (2002) Femoral Artery Inflow in Relation to External
and Total Work Rate at Different Knee Extensor Contraction Rates.
Journal
of
Ap-
plied
Physiology
, 92, 1325-1330. https://doi.org/10.1152/japplphysiol.00848.2001
[12] Osada, T. and Rådegran, G. (2009) Femoral Artery Blood Flow and Its Relationship
to Spontaneous Fluctuations in Rhythmic Thigh Muscle Workload.
Clinical
Physi-
ology
and
Functional
Imaging
, 29, 277-292.
https://doi.org/10.1111/j.1475-097X.2009.00868.x
[13] Osada, T., Katsumura, T., Hamaoka, T., Inoue, S., Esaki, K., Sakamoto, A., Murase,
N., Kajiyama, J., Shimomitsu, T. and Iwane, H. (1999) Reduced Blood Flow in Ab-
dominal Viscera Measured by Doppler Ultrasound during One-Legged Knee Exten-
sion.
Journal
of
Applied
Physiology
, 86, 709-719.
https://doi.org/10.1152/jappl.1999.86.2.709
[14] Shoemaker, J.K., Hodge, L. and Hughson, R.L. (1994) Cardiorespiratory Kinetics
T. Osada
DOI:
10.4236/wjcd.2020.1012076 808
World Journal of Cardiovascular Diseases
and Femoral Artery Blood Velocity during Dynamic Knee Extension Exercise.
Journal
of
Applied
Physiology
, 77, 2625-2632.
https://doi.org/10.1152/jappl.1994.77.6.2625
[15] Hughson, R.L., Shoemaker, J.K., Tschakovsky, M.E. and Kowalchuk, J.M. (1996)
Dependence of Muscle VO2 on Blood Flow Dynamics at Onset of Forearm Exer-
cise.
Journal
of
Applied
Physiology
, 81, 1619-1626.
https://doi.org/10.1152/jappl.1996.81.4.1619
[16] Osada, T., Saltin, B., Mortensen, S.P. and Rådegran, G. (2012) Measurement of the
Exercising Blood Flow during Rhythmical Muscle Contractions Assessed by Dopp-
ler Ultrasound: Methodological Considerations.
Journal
of
Biomedical
Science
and
Engineering
, 5, 779-788. https://doi.org/10.4236/jbise.2012.512A098
[17] Hiatt, W.R., Hirsch, A.T. and Regensteiner, J.G. (2001) Peripheral Arterial Disease.
CRC Press, Boca Raton.
[18] Osada, T., Saltin, B. and Rådegran, G. (2013) Assessment of Voluntary Rhythmic
Muscle Contraction-Induced Exercising Blood Flow Variability Measured by Doppler
Ultrasound.
Open
Journal
of
Molecular
and
Integrative
Physiology
, 3, 158-165.
https://doi.org/10.4236/ojmip.2013.34021
[19] Osada, T., Ishiyama, M. and Ueno, R. (2019) Voluntary Thigh Muscle Strength with
Resection Stump-Dependent Blood Flow and Vasodilation in an Amputated Lower
Leg with Total Surface Bearing Prosthesis during Dynamic Knee Extensor: A Case
Trial.
Open
Journal
of
Therapy
and
Rehabilitation
, 7, 151-169.
https://doi.org/10.4236/ojtr.2019.74011
[20] Osada, T. and Rådegran, G. (2016) Difference in Muscle Blood Flow Fluctuations
between Dynamic and Static Thigh Muscle Contractions: How to Evaluate Exercise
Blood Flow by Doppler Ultrasound.
Physical
Medicine
and
Rehabilitation
Research
,
1, 128. https://doi.org/10.15761/PMRR.1000128
[21] Thomas, K.N., Cotter, J.D., Lucas, S.J., Hill, B.G. and van Rij, A.M. (2015) Reliabili-
ty of Contrast-Enhanced Ultrasound for the Assessment of Muscle Perfusion in
Health and Peripheral Arterial Disease.
Ultrasound
in
Medicine
&
Biology
, 41,
26-34. https://doi.org/10.1016/j.ultrasmedbio.2014.06.012
[22] Duerschmied, D., Olson, L., Olschewski, M., Rossknecht, A., Freund, G., Bode, C.
and Hehrlein, C. (2006) Contrast Ultrasound Perfusion Imaging of Lower Extremi-
ties in Peripheral Arterial Disease: A Novel Diagnostic Method.
European
Heart
Journal
, 27, 310-315. https://doi.org/10.1093/eurheartj/ehi636
[23] Meneses, A.L., Nam, C.Y., Bailey, T.G., Magee, R., Golledge, J., Hellsten, Y., Keske,
M.A., Greaves, K. and Askew C.D. (2018) Leg Blood Flow and Skeletal Muscle Mi-
crovascular Perfusion Responses to Submaximal Exercise in Peripheral Arterial
Disease.
American
Journal
of
Physiology
—
Heart
and
Circulatory
Physiology
, 315,
H1425-H1433. https://doi.org/10.1152/ajpheart.00232.2018
[24] Baker, W.B., Li, Z., Schenkel, S.S., Chandra, M., Busch, D.R., Englund, E.K.,
Schmitz, K.H., Yodh, A.G., Floyd, T.F. and Mohler, E.R. (2017) Effects of Exercise
Training on Calf Muscle Oxygen Extraction and Blood Flow in Patients with Peri-
pheral Artery Disease.
Journal
of
Applied
Physiology
, 123, 1599-1609.
https://doi.org/10.1152/japplphysiol.00585.2017