Journal of Cardiovascular Nursing

Vol. 34, No. 2, pp 130Y133 x Copyright B 2018 Wolters Kluwer Health, Inc. All rights reserved.

Acute Lower Leg Heating Increases Exercise

Capacity in Patients With Peripheral
Artery Disease
Thomas K. Pellinger, PhD; Catherine B. Neighbors, MS; Grant H. Simmons, PhD

Background/Objective: In this pilot study, we tested the hypothesis that acute lower leg heating (LLH) increases
postheating popliteal artery blood flow and 6-minute walk distance in patients with peripheral artery disease (PAD).
Methods: Six patients (5 male, 1 female) with PAD (69 T 6.9 years; claudication: ankle-brachial index G 0.90)
Downloaded from http://journals.lww.com/jcnjournal by BhDMf5ePHKbH4TTImqenVKFjfEjHw8MEuMluX8dhfw8ekTHaY8gmznJUE7nN4ahKnXC4N62B5qs= on 02/28/2019

participated in 3 randomized treatment sessions (2Y7 days apart): control or bilateral LLH conducted via water bath
immersion (42-C; ~40-cm depth) for either 15 or 45 minutes. Popliteal artery blood flow (Doppler ultrasound) and
arterial pressure were measured before and after LLH. Six-minute walk distance was measured on the control day and
each experimental day 35 minutes post-LLH. Results: Popliteal artery blood flow increased after heating in a
duration-dependent manner (P G .05, postheating vs control for both heating conditions and between them).
Six-minute walk distance increased by 10% and 12% after 15- and 45-minute heating treatments, respectively
(P G .05 vs control session). Conclusions: Lower leg heating, for as short as 15 minutes, increases postheating
leg perfusion and exercise capacity in patients with PAD.
KEY WORDS: blood flow, claudication, six-minute walk, water immersion

P eripheral artery disease (PAD), which affects

155 million people worldwide,1 is a debilitating
condition characterized by functional impairment, exer-
cise intolerance, and an increased risk of cardiovascular
mortality.2 Patients with PAD face a sobering prognosis
whereby pain and fatigue-related exercise intolerance
cause a physically inactive lifestyle, which contributes
to a further decline in functional capacity and quality
of life.3,4 The role of exercise in staving off morbidity
progression is well established,5,6 but adherence to exercise
recommendations is attenuated outside the clinical setting
for patients with PAD, because of exercise intolerance and
a lack of external motivation.7,8 Thus, the amelioration of
acute exercise tolerance is a goal that, if achieved, could
have a positive impact on physical activity engagement in
addition to immediate beneficial effects on exercise
Thomas K. Pellinger, PhD
Associate Professor of Applied Physiology, Department of Health
Sciences, Salisbury University, Maryland.
Catherine B. Neighbors, MS
Simulation Coordinator for the Richard A. Henson Medical Simulation
Center, Department of Nursing, Salisbury University, Maryland.
Grant H. Simmons, PhD
Adjunct Assistant Professor, Department of Medical Pharmacology &
Physiology, University of Missouri, Columbia.
This research was supported by the Salisbury University Faculty Mini-Grant.
The authors have no conflicts of interest to disclose.
Correspondence
Thomas K. Pellinger, PhD, Salisbury University, 312-C Devilbiss Hall, 1101
Camden Ave, Salisbury, MD 21801-6860 (tkpellinger@salisbury.edu).
DOI: 10.1097/JCN.0000000000000510
capacity. It is therefore important to explore simple,
inexpensive, clinic- and home-based strategies that imme-
diately improve exercise capacity in patients with PAD.
Lower leg heating (LLH) is one strategy easily
deployed in both the clinic and home settings, which
may acutely increase exercise capacity in patients
with PAD. Acute limb heating (1) increases popliteal
artery blood flow during9 and after10 heating, (2)
increases perfusion of the distal microcirculation to
both the skin and muscle,11 and (3) increases
postheating vasoreactivity of the conduit arteries.12
Notably, blood flow changes with heating occur
while limb oxygen consumption is unaffected.13 Recent
research indicates that acute lower limb heating may
induce beneficial cardiovascular effects in patients with
PAD.10,14 However, to our knowledge, no investigation
has examined the impact of lower limb heating on both
leg perfusion and exercise capacity in this population.
The aim of this pilot study therefore was to test the
hypothesis that acute LLH (for 15 or 45 minutes)
increases postheating popliteal artery blood flow and
6-minute walk distance (6MWD) in patients with PAD.
Methods
Ethical Approval
This pilot study was approved by the institutional review
board of Salisbury University. Each subject gave his/her
informed written consent before participation.

130

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

 LLH Increases Exercise Capacity in Patients With PAD 131

Subjects Mean blood velocities and diameters of the popliteal

Six individuals (5 men and 1 woman) with PAD (claudica-
tion, Fontaine stage II), aged 69 T 6.9 years (62Y81 years),
participated in this study. Inclusion criteria included a
resting ankle-brachial index of less than 0.90, a body
mass index of less than 35 kg/m2, and free of severe
walking limitations due to comorbidity. For all study
visits, subjects reported to the laboratory at least 3 hours
postprandial, having refrained from alcohol consump-
tion and exercise for 24 hours and consumption of
caffeine for 12 hours. Subjects were instructed to take
medications normally, as prescribed by their physi-
cians. Please see the Table for subject characteristics.
Experimental Protocol
Subjects reported to a temperature-controlled laboratory
(21-CY22-C) for parallel experiments on three separate,
randomized study visits, each separated by 2 to 7 days.
Each study day, subjects were laid supine and instru-
mented with a 6-lead electrocardiogram (AD Instru-
ments Dual Bio Amplifier/ECH 12-Lead Switch Box,
Colorado Springs, Colorado). After 10 minutes of quiet
rest, baseline measurements of single-leg popliteal artery
blood flow (Doppler ultrasound; Philips Sonos 4500
ultrasound system, Amsterdam, the Netherlands) and
arterial pressure (automated oscillometric device; Welch
Allyn Vital Signs Monitor, Skaneateles Falls, New
York) were taken in triplicate. Blood flow was
measured on each subject"s most affected leg, as
indicated by the ankle-brachial index measurements
furnished by his/her physician and confirmed by the
subject"s subjective report of signs and/or symptoms. For
patients with no reported differences between legs,
blood flow in the right leg was measured.
TABLE Subject Characteristics
Age, y
Sex, M/F
Height, cm
Weight, kg
Body mass index, kg/m2
Resting ankle-brachial index
Systolic blood pressure, mm Hg
Diastolic blood pressure, mm Hg
Mean arterial pressure, mm Hg
Concomitant medications, no. patients taking
ACE inhibitor
Statin
"-adrenergic blocker
Anticoagulant
Calcium channel blocker
Diuretic
Metformin
Values are mean (SD); ankle-brachial index values are from the most
affected leg.
Abbreviations: ACE, angiotensin-converting enzyme; F, female; M, male.
artery were measured using a linear ultrasound probe
(Philips 11-3L Ultraband trapezoidal linear-array vascu-
lar transducer, Amsterdam, the Netherlands). The entire
width of the artery was insonated with an angle of 60-,
and velocity measurements were taken immediately
before diameter measurements. A Doppler Audio Trans-
lator (Penn State Heart & Vascular Institute) was used
to convert the 2 analog Doppler audio signals into a
proportional time-varying flow velocity waveform that
was recorded by the data acquisition system.15 Popliteal
artery blood flow was calculated as artery cross-sectional
area multiplied by popliteal mean blood velocity and
reported as ml I minj1. Popliteal vascular conductance
was calculated as popliteal artery blood flow/mean arterial
pressure and expressed as ml I minj1 I mm Hgj1.
After baseline measurements, subjects were moved
to a seated position to undergo bilateral LLH for either
15 or 45 minutes or 15 minutes of quiet rest (control
visit). Quiet rest was used during the control visit because
immersion of the leg in thermoneutral (room tem-
perature) water would increase heat loss beyond that
observed with thermoneutral air exposure, amounting
to a mild cold exposure over the leg with resultant
impacts on resting limb blood flow. The 45-minute
duration of LLH was based on the current guidelines
for supervised exercise therapy for patients with PAD.5
The 15-minute duration of LLH was included as a pos-
sible alternative to the 45-minute session, to which
patients with PAD might be more compliant. Lower
leg heating was carried out via water bath immersion
at a depth of approximately 40 cm with the water tem-
perature maintained at 42-C, via a water circulator/
temperature controller device (VWR International, Radnor,
Pennsylvania).
Immediately after LLH (or control), subjects returned
to the supine position and measurements of popliteal
artery blood flow and arterial pressure were taken in
triplicate at 10, 20, and 30 minutes. After these
69.0 (6.9) measurements (35 minutes after intervention), subjects
5/1
174.0 (16.0) were instrumented with a wireless 6-lead electrocar-
88.9 (23.5) diogram (Norav 1200W Stress ECG System, Wiesbaden,
28.8 (4.3) Germany) and performed a self-paced 6-minute walk
0.69 (0.15) test.16 Subjective ratings of perceived exertion, clau-
131.0 (7.0) dication, and dyspnea were collected each minute
72.7 (8.0)
92.1 (6.4) during the walk. In addition, subjects were asked to
report their onset of claudication symptoms, if
4 applicable.
4
2
2 Statistics
1
1 The effect of heating condition (or control) on 6MWD
1 and distance to the onset of claudication was assessed
by a 1-way repeated-measures analysis of variance.
The effects of heating condition (or control) and heat
application (pre/post) on popliteal artery blood flow

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

132 Journal of Cardiovascular Nursing x March/April 2019
and vascular conductance were assessed by a 2-way
repeated-measures analysis of variance. The Holm-
Sidak post hoc test was used where appropriate; !
was set to .05. All values are reported as mean T
SEM, unless otherwise noted.
Results
Subject characteristics are presented in the Table. The
effects of acute LLH for 15 and 45 minutes on resting
popliteal artery blood flow (30 minutes postheating)
and 6MWD are displayed in the Figure. There was a
significant time (pre/post)  session interaction effect
on popliteal artery blood flow (F = 11.059, P = .003).
The 15-minute LLH session increased popliteal artery
blood flow from 89.1 T 11.9 to 172.6 T 19.8 mLI
minj1 (93.7%; P = .019), whereas the 45-minute
LLH session increased popliteal artery blood flow
from 78.9 T 13.5 to 266.8 T 57.8 mL I minj1 (238.2%;
P = .002). The magnitude of popliteal artery blood flow
postheating increased in a (heating) duration-dependent
FIGURE. Impact of acute lower leg heating on resting popliteal
artery blood flow and 6-minute walk distance (6MWD) (upper
and lower panels, respectively; n = 6). *P G .05 versus control
condition for 6MWD. yP G .05 postheating (30 minutes)
versus preheating popliteal artery blood flow. Although not
depicted using symbols, the magnitude of popliteal artery
blood flow postheating increased in a (heating) duration-
dependent manner (P G .05 vs control for both heating
conditions and between 15- vs 45-minute heating). Values
are mean T SEM.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
manner (P G .05 vs control for both heating conditions
and between 15- vs 45-minute heating). Baseline pop-
liteal artery blood flow was similar between condi-
tions, and responses in popliteal vascular conductance
mirrored the blood flow responses.
Lower leg heating increased 6MWD from 1021.7 T
109.3 feet in the control session to 1126.0 T 121.8 feet
(10.2%; P = .018) in the 15-minute session and 1139.9 T
131.0 feet (11.6%; P = .009) in the 45-minute session.
Distance walked was not different between heating
sessions. Rating of perceived exertion in the final
minute of exercise was lower in the 45-minute session
(13.0 T 0.8) than the control and 15-minute sessions
(14.0 T 0.7 and 14.2 T 0.5, respectively; both Ps G .05),
whereas distance to the onset of claudication symp-
toms was not different between conditions (P = .18).
Discussion
The goal of this pilot study was to determine the effect
of acute LLH (for 15 or 45 minutes) on resting
popliteal artery blood flow and 6MWD in patients
with PAD. In support of our hypothesis, both 15- and
45-minute heating sessions increased postheating pop-
liteal artery blood flow and 6MWD, evoking similar
improvements in distance walked (Q10%). Furthermore,
LLH reduced perceived exertion even while walking pace
increased, albeit only in the 45-minute heating session.
These results suggest that as little as 15 minutes of LLH,
via water immersion, increases leg perfusion and improves
acute walking capacity in these patients. Thus, LLH shows
promise as a novel and practical intervention to acutely
improve exercise capacity in patients with PAD.
There are some limitations to our preliminary inves-
tigation. First, this study was performed on a relatively
small sample size; however, all subjects demonstrated
increased popliteal artery blood flow and improved
6MWD with heating. Second, although we demonstrated
that both popliteal artery blood flow and 6MWD
increased after LLH, the degree to which these improve-
ments in walking capacity can be attributed to increases
in leg perfusion, per se, is unclear. It is possible that
another stimulus associated with LLH, such as warming
of the muscles, thus altering enzyme kinetics, may have
contributed to the improved 6MWD in these patients.
Along those lines, 6MWD after 45 minutes of LLH was
only slightly farther than 6MWD after 15 minutes of
LLH, despite substantially greater increases in popliteal
artery blood flow after the 45-minute intervention. It is
feasible that there is a blood flow threshold that must be
met to adequately perfuse the working skeletal muscle
in these patients and further increases in blood flow may
hyperperfuse the muscle, thus delivering more oxygen
and nutrients than are needed to support the metabolic
demand of the exercise bout. Finally, although there is a
trend for a delayed onset of reported claudication, this

What’s New and Important
h As short as 15 minutes of LLH improves postheating
popliteal artery blood flow and 6MWD in patients with
claudication.
h Lower leg heating is an inexpensive intervention that
can be easily implemented in both clinic and home
settings.
h Lower leg heating shows promise as a strategy to
improve exercise capacity in patients with PAD.
subjective measure was not statistically significant.
Future studies may help to further elucidate the mech-
anisms underlying LLH as a tool to improve walking
capacity in patients with PAD.
Perspectives and Clinical Significance
The current study is the first to demonstrate that acute
LLH increases walking capacity in patients with PAD.
Lower leg heating is a safe and inexpensive intervention
that can be easily implemented in both clinic and home
settings; therefore, it has the potential to improve
exercise capacity in this population. If used regularly,
LLH may be one of several interventions to improve
exercise adherence in patients with PAD,17 thereby
allowing the beneficial effects of exercise therapy to be
observed and sustained with both home- and clinic-
based exercise programs. These preliminary findings
set the stage for future investigations examining the role
of LLH as a therapy for patients with PAD.
Acknowledgments
The authors thank the subjects who volunteered for
this study. They also thank Dr Steven Hearne for his
consultation and Christopher Evans, Joel Anderson,
Rachel Prestridge, and Katherine Timmons for their
technical assistance during this study.
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