Training & Testing Thieme

Time Course Change in Muscle Swelling: High-Intensity vs. Blood

Flow Restriction Exercise

Authors
Eduardo D.S. Freitas1, Christopher Poole2, Ryan M. Miller1, Aaron David Heishman1, Japneet Kaur1, Debra A. Bemben3,
Michael Bemben1

Affiliations
1 Health & Exercise Science, University of Oklahoma,
Norman, United States
2 Department of Health and Exercise Science, University of
Oklahoma, Norman, United States
3 Department of Health and Exercise Science, University of
Oklahoma Norman, Norman, United States
ABS tR AC t
This study determined the time course for changes in muscle
swelling and plasma volume following high (HI) and low-inten-
sity resistance exercise with blood-flow restriction (LI-BFR). Ten
male participants (22.1 ± 3.0 yrs) completed three experimen-
tal conditions: high-intensity exercise (HI - 80 % of 1RM), low-
intensity exercise with BFR (LI-BFR –20 % of 1RM, and
160 mmHg of BFR), and control (CON – no exercise or BFR).

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Key words Muscle cross-sectional area (mCSA), muscle thickness, thigh
occlusion training, strength exercise, cell swelling, hemato- circumference, and percentage change in plasma volume
crit, pQCT, ultrasound (PV %∆) were measured. mCSA was significantly greater than
rest values at 15 min post-exercise (p < 0.01) for HI and LI-BFR,
accepted after revision 02.08.2017
and at 75 min post-exercise (p < 0.01) for HI. Muscle thickness
Bibliography was significantly greater than rest immediately post-exercise
DOI https://doi.org/10.1055/s-0043-118342 (p < 0.01) and 30 min post-exercise (p < 0.01) for HI and LI-BFR,
Published online: 2017 and at 60 min post-exercise for HI (p = 0.01). Muscle thickness
Int J Sports Med was greater for BFR immediately post-exercise compared to HI
© Georg Thieme Verlag KG Stuttgart · New York (p = 0.01) post-exercise. Thigh circumference was significantly
ISSN 0172-4622 greater from rest at 15 min post-exercise (p = 0.01) and at
75 min post-exercise for both LI-BFR (p = 0.03) and HI (p < 0.01).
Correspondence PV %∆ significantly decreased from rest immediately post-ex-
Mr. Eduardo D.S. Freitas ercise for both HI (p < 0.01) and LI-BFR (p < 0.01). In conclusion,
University of Oklahoma BFR exercise induces changes in muscle swelling and plasma
Health & Exercise Science volume similar to those observed at high-intensities.
Asp ave
73019, Norman
United States
Tel.: + 1/405/3255 211, Fax: + 1/405/3255 211
eduardofreitas@ou.edu

Introduction a sufficient enough stimulus for increasing muscular hypertrophy

Traditional high-intensity exercise can induce significant increases
in muscle hypertrophy and strength through a variety of different
mechanisms [15, 33, 36]. Initially, research suggested that the pri-
mary mechanism for muscle hypertrophy was the release of ana-
bolic hormones, such as growth hormone and testosterone [3, 19].
Although hormonal responses seem to play an important role in
muscle growth, alternative mechanisms have also been postulat-
ed to provide a significant contribution to the physiological adap-
tations of skeletal muscle in response to high intensity resistance
exercise [35]. In fact, recent research has provided evidence that
simply creating the appropriate hormonal milieu may not provide
and strength [45, 46]. In this regard, Spiering et al. [38] proposed
a mechanism, in addition to the hormonal responses, that involves
a post-exercise inflammatory response that would trigger intracel-
lular molecular pathways inside that ultimately would increase DNA
translation and transcription, resulting in subsequent muscle hy-
pertrophy and growth.
Several factors may impact the amount and the intensity of
muscle contractions executed during exercise, ultimately influenc-
ing the magnitude of the post-exercise inflammatory response.
Therefore, many studies have been designed to manipulate exer-
cise intensity, volume, and frequency in an attempt to control for

Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
 Training & Testing
▶table 1 Baseline Subject’s Characteristics (n = 10).
Demographics:
Age (yrs) 22.1 ± 3.0
Height (cm) 180.7 ± 5.7
Weight (kg) 80.2 ± 15.9
Body Fat ( %) 23.2 ± 5.9
Muscular Strength:
Leg Press 1 RM (kg) 170 ± 39.8
Leg Extension 1 RM (kg) 100.6 ± 20.1
Leg Curl 1 RM (kg) 94.3 ± 20.1
1 RM: One-repetition maximum. Values are mean ± SD
the impact of each variable on post-exercise inflammation
[6, 13, 39]. Historically, traditional resistance exercise performed
at moderate to high-intensities, ranging from 65 % to 85 % of 1 Rep-
etition Maximum (1RM) with low to moderate volumes have been
recommended in order to produce positive adaptations in muscle
strength and hypertrophy [4]. However, low-intensity resistance
training to failure has also been shown to induce similar muscular
adaptations but the reduction in exercise intensity necessitates a
very large increase in exercise volume to achieve similar muscular
outcomes, making low intensity resistance training less practical
[29]. One problem with acute high-intensity exercise is that it can
cause muscle damage as a result of micro tears of the muscle fib-
ers resulting in delayed onset muscle soreness (DOMS), an inflam-
matory response from the immune system, and a fluid shift into
the cell causing swelling [12]. The resulting pain associated with
DOMS usually begins about 8 h after exercise and last from 24 up
to 96 h post-exercise [8, 12].
Since increased intracellular fluid has been associated with stim-
ulating protein synthesis and initiating muscle hypertrophy
[23, 26], low-intensity resistance exercise with blood flow restric-
tion (LI-BFR) has also been used to induce significant muscle swell-
ing following acute exercise in an attempt to stimulate muscle hy-
pertrophy [49]. Blood flow restriction (BFR) training has consist-
ently been reported to elicit significant improvements in muscle
size and strength similar to those observed with high-intensity re-
sistance training, even at very low-intensities (20 %–50 % of 1 RM)
[23, 27, 30]. Bryk et al. compared the effectiveness of high-inten-
sity training and low-intensity training with BFR on strength levels
in women with knee osteoarthritis and observed similar benefits
using both methods of training [7]. This makes BFR training appli-
cable for people who cannot withstand the high-intensities of tra-
ditional resistance exercise such as those recovering from injury/
disease, the elderly, and even athletes, as part of their traditional
training programs [41, 44].
All of the physiological mechanisms involved in the positive ad-
aptations associated with BFR training are not completely under-
stood, but it has been speculated that acute and chronic increases
in hormone secretions [28, 34], increased motor unit recruitment,
especially Type II fibers increased muscle activation [47], muscle
swelling [49], inhibition of myostatin gene expression [22], and ac-
tivation of anabolic molecular pathways [11, 31] play an important
role. From the large number of potential proposed mechanisms,
muscle swelling has recently received a significant amount of at-
Thieme
tention. Loenneke et al. [24] investigated the immediate post-ex-
ercise plasma volume changes and muscle swelling responses fol-
lowing exercise with BFR and high intensity exercise and suggested
that the muscle swelling observed was due to increased intramus-
cular fluid caused by a shift in extracellular fluid into the muscle cell
initiating a cascade of biomolecular events that ultimately lead to
muscle hypertrophy [26]. Since muscle swelling has repeatedly
been proposed as a potential mechanism for stimulating protein
synthesis (muscle hypertrophy) and the fact that high intensity re-
sistance training can induce DOMS and damage (also contributing
to the swelling process) which can last for up to 96 h, it seemed crit-
ical to evaluate changes in limb size for both for both types of ex-
ercise protocols (BFR and high intensity resistance training) to de-
termine if the swelling observed acutely with BFR (low intensity)
exercise also remained for a prolonged period of time (without the
consequences of muscle damage associated with high intensity ex-
ercise).
Therefore, the main purpose of this study was to determine the
time course change in both muscle swelling and plasma volume
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following an acute bout of low-intensity (20 % 1RM) resistance ex-
ercise with BFR in comparison to a traditional high-intensity (80 %
1RM) resistance exercise with no BFR. It was hypothesized that BFR
exercise would induce a greater amount of muscle swelling and a
larger decrease in plasma volume compared to traditional high-in-
tensity exercise that will return to baseline values within 24 h.
Methods
Participants
Ten recreationally trained males (▶table 1) aged between 18 and
30 years volunteered for the present study. Individuals that were
not performing any resistance exercise program for the past three
months or high intensity aerobic exercise more than two days per
week within the last three months, with no orthopedic problems/
injuries that could compromise exercise performance, normoten-
sive, with no cardiovascular or thromboembolic disease, non-smok-
ers, and normal weight (e. g. body mass index ≥ 18 and < 30 kg/m2)
were included. Participants were excluded if they were not able to
complete the exercise protocols, if they were not able to attend the
laboratory at the times scheduled, or if they requested to be re-
moved from the study. This research was approved by the Institu-
tional Review Board of the University of Oklahoma and it conforms
to the standards set by the Declaration of Helsinki and it also meets
the ethical standards of the International Journal of Sports Medi-
cine [14]. All participants gave written, informed consent before
participation in the study.
Study design
A cross-over within subjects study design was utilized to examine
the time course of increased intramuscular fluid following a single
bout of high-intensity exercise compared to a bout of low-intensi-
ty exercise with BFR. The study lasted for four weeks with a total of
16 visits for each participant. During visit 1, participants filled out
a health status questionnaire, a Physical Activity Readiness Ques-
tionnaire (PAR-Q), and a research privacy form; had their body com-
position assessed by Dual Energy X-ray Absorptiometry (DXA) (GE
Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
Medical Systems, Lunar Prodigy encore software version 10.50.086,
Madison, WI); and performed 1 RM tests to determine the loads to
be used during exercise. One week later, participants were random-
ly assigned to one of three conditions: 1) low-intensity (20 % 1RM)
exercise with BFR (LI-BFR), 2) high-intensity (80 % 1RM) exercise
without BFR (HI), and 3) control with no exercise and no BFR (CON).
All exercise trials were conducted at least one week apart. Periph-
eral quantitative computed tomography (pQCT) (XCT 3000, Stratec
Medizintechnik GmbH, Pforzheim, Germany) and thigh circumfer-
ence measurements were made at baseline before exercise and
15 min, 75 min, 24 h ( ± 1), 48 h ( ± 1), 72 h ( ± 1), and 96 h ( ± 1) post-
exercise to assess muscle volume. Ultrasound measurements (FF
Sonic UF-4500, Fukuda Denshi, Tokyo, Japan) were also performed
at baseline, immediately post-exercise, 30 min post-exercise, and
1 h post-exercise to assess quadriceps and hamstrings muscle thick-
ness. Additionally, blood samples were drawn by finger prick to as-
sess plasma volume at baseline, immediately post, and 1 h post-
exercise. The measurements performed in the CON condition were
completed in the same exact time course as the exercise condi-
tions. Participants were asked to record nutrient intake 24 h before
exercise and 24 h post-exercise for each condition. Additionally, the
investigators assessing muscle size and mass by DXA, pQCT, cir-
cumferences, and Ultrasound were blinded to the testing condi-
tions.
One-maximum repetition test (1 RM)
All participants performed a 1 RM test for the semi reclined two leg
press, and the seated knee extension, and knee flexion to deter-
mine the load to be used during the acute bout of exercise used to
assess muscle swelling. Following a 5 min warm-up on a stationary
bike, participants then performed 1 set of 8 to 10 repetitions at
about 50 % of 1RM and 1 set of 3 to 4 repetitions at approximately
80 % of 1 RM. Following the warm-up sets, the load was increased
and participants performed the first trial in which one repetition
was completed with proper form through a full range of motion.
The load was continuously increased in the subsequent attempts
(up to maximum of 5 attempts) until participants could not com-
plete one repetition, or the load was decreased if the 1 RM was over-
estimated. Two-minute rest intervals were provided between each
trial and each of the 3 exercises.
Body composition
Total body composition was assessed by DXA. Participants were
positioned supine on the DXA table and centered within the scan-
ning area, with both arms positioned at the side of the body. Vel-
cro straps were used to hold subject’s feet together during assess-
ment. Scan speed was set according to the participant’s thickness
at the naval (thick = > 25 cm; standard = 12–25 cm; thin = < 13 cm).
Muscle cross-sectional area (mCSA)
Peripheral quantitative computed tomography (pQCT) was used
to assess muscle cross-sectional area at the 50 % site of the right
femur at baseline and 15 min, 75 min, 24 h ( ± 1), 48 h ( ± 1), 72 h
( ± 1), and 96 h ( ± 1) post-exercise. Participants were seated with
their upper leg centered in the gantry of the pQCT machine. A scout
scan was first performed to visualize and mark a reference line at
the distal end of the femur in order to then perform the measure-
Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
ment at the 50 % femur site in accordance with the reference line.
Analysis thresholds were used to distinguish between fat, muscle,
and bone. Thresholds used for mCSA analysis at the 50 % femur site
were Contmode 31, Peelmode 2, Threshold1 40, Threshold2 40,
Cortmode 4, Threshcrt1 710, and Threshcrt2 40. Each measure-
ment was performed by the same trained technician.
Muscle swelling
Muscle swelling was determined by muscle thickness measure-
ments performed both anteriorly (quadriceps) and posteriorly
(hamstrings) on the right thigh at baseline, immediately post,
30 min, and 1 h post-exercise for each condition using an ultra-
sound machine (FF Sonic UF-4500, Fukuda Denshi, Tokyo, Japan).
A 5-MHz scanning head covered with transmission gel was placed
at the 50 % femur site for both sites (perpendicular to the tissue in-
terface). Once an appropriate image was obtained, it was printed
for later analysis. Muscle thickness was defined as the distance be-
tween the adipose tissue interface and the bone interface. Each
measurement was performed by the same trained technician.
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Thigh circumference
Thigh circumference was measured at the 50 % site of the femur
site following each pQCT scan. The measurements were performed
to the nearest tenth of a centimeter and two measurements with-
in two millimeters of each other were completed and averaged at
each time point.
Plasma volume
Blood from a finger prick was collected to determine the percent
change in plasma volumes at baseline, immediately post, and 1 h
post trials. After sterilization, participants had their index finger
pricked and a blood drop was collected into a heparinized plastic
micro-hematocrit tube and then centrifuged for to separate hem-
atocrit from plasma. Hematocrit to plasma percentage was deter-
mined using a digital hematocrit reader (StatSpin, Norwood, MA)
in each sample. Percent change ( %ΔPV) in plasma volume were de-
termined by the following equation proposed by Van Beaumont [5]
and previously used by our research group [37]:
100 100 (HctPre Hct Post )
% PV
100 Hct Pre Hct Post
Exercise protocols
HI condition
Participants warmed-up on a stationary bike for 5 min, and then
performed 3 sets of 8 to 10 repetitions at 80 % 1 RM on the leg
press, knee extension, and leg curl machines (Cybex Strength Sys-
tems, Medway, MA, USA). Two min rest was given between sets and
between different exercises.
LI-BFR condition
Participants also warmed-up for 5 min on a stationary bike before
exercise. Then, they were seated and fitted with a 5 cm wide nylon
cuffs (Hokanson, Bellevue, WA 98005), placed at the most proxi-
mal portion of each thigh and inflated to 120 mmHg for 30 s and
deflated for 10 s, then increments of 10 mmHg were made and this
 Training & Testing Thieme

▶table 2 Three day average total caloric intake, macronutrient intake, Dietary monitoring
and percentages of total daily caloric intake across each experimental A three-day nutritional log was used to determine nutrition habits
condition.
one day prior to each exercise condition, the day of the exercise,
Exercise Condition and the day post-exercise. This log was used to confirm the consist-
LI-BFR (n = 9) HI (n = 9) CON (n = 9)
ency of the dietary habits across the study period by assessing the
3-Day Avg: individual caloric and macronutrient intakes.
Total CI (kcal) 2110.9 ± 452.4 1870.6 ± 625.7 1689.4 ± 836.7
CHO Intake (g) 279.4 ± 104.8 204.0 ± 72.6 200.0 ± 98.3
Statistical analysis
Data normality was confirmed by the Kolmogorov Smirnov test.
Protein Intake (g) 87.6 ± 16.0 101.0 ± 32.5 84.6 ± 39.6
Sample size was determined using Cohen’s calculations for statis-
Fat Intake (g) 71.5 ± 19.9 75.8 ± 34.4 58.8 ± 35.7
tical power and an estimated small ES of .38, which then required
%TDCI:
a sample size of n = 9 in order to achieve a statistical power of 0.80.
Carbohydrate 51.5 ± 10.6 43.6 ± 8.2 47.5 ± 7.0
A two-way repeated measures ANOVA (condition [HI, LI-BFR, CON]
Protein 17.6 ± 6.8 21.6 ± 12.4 20.3 ± 6.0
x time [baseline and post-exercise measurements]) was used to
Fat 31.1 ± 7.9 36.5 ± 8.8 31.6 ± 7.1
test condition and time main effects and the interaction between
LI-BFR: Low-Intensity Resistance Exercise with Blood Flow Restriction. condition and time for each variable. Whenever a significant con-
HI: High-Intensity Resistance Exercise. CON: Non-Exercise Control. dition x time interaction was verified, the statistical model was de-
CI: Caloric Intake. CHO: Carbohydrate. %TDCI: Percent Total Daily
composed by examining the simple effects with separate one-way
Caloric Intake. Values are mean ± SD
repeated measures ANOVAs with Bonferroni correction factors for

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each group and time point. Additional repeated measure ANOVAs
were used to determine if any differences existed in total caloric or
1.5 macronutrient intakes across conditions. The alpha level was set at
0.05 for all analyses. Data are presented as mean ± SD. The PASW
†‡§
Statistics 18 for Windows (Chicago, IL) was used to run all the anal-
Quadriceps thickness (cm)

1.0
yses.
†‡
0.5

0.0
– 0.5
0 min 30 min
LI-BFR HI
▶Fig. 1 Quadriceps muscle thickness at rest and post-exercise
across each condition. LI-BFR: Low-Intensity Resistance Exercise with
Blood Flow Restriction; HI: High-Intensity Resistance Exercise; CON:
Non-Exercise Control. * Significant increase from Pre (p < 0.05).
†Significant difference from LI-BFR to CON (p < 0.05). ‡Significant
difference from HI to CON (p < 0.05). §Significant difference from HI
to LI-BFR (p < 0.05). Values are mean absolute change ± 95 % confi-
dence interval.
cycle of inflation and deflation was repeated until the exercise tar-
get pressure of 160 mmHg was reached. Participants then per-
formed one set of 30 repetitions followed by 3 sets of 15 repeti-
tions with 30 s rest between sets and between different exercises.
Leg press, knee extension, and leg curl exercises were performed
at 20 % of 1 RM. The cuffs remained inflated during rest intervals
and between exercises. The cuffs were deflated and removed after
post-exercise ultrasound measurements.
CON condition
Subjects did not perform any exercise and rested in a seated posi-
tion for the same quantity of time spent during the experimental
conditions.
Results
Participant’s characteristics
Participant’s demographic characteristics and strength measures
are presented in ▶ table 1. From the 10 participants that volun-
60 min
teered for this study, one participant did not complete a three-day
CON
food log and three participants did not complete a pQCT scan and
a circumference measurement. These three participants were still
included in the statistical analyses for the variables that they had
completed measurements but were excluded from the ANOVA
analyses.
Total caloric and macronutrient intakes
▶ table 2 presents the three-day caloric and macronutrients in-
takes and percentages of total caloric intake for each condition.
There was a significant (p = 0.02) difference in carbohydrate intake
across conditions, however, follow up comparisons revealed no sig-
nificant condition differences (p > 0.05). There were no significant
differences for total caloric (p = 0.11), protein (p = 0.28), or fat in-
takes (p = 0.29) across conditions.
Muscle thickness
As illustrated in ▶Fig. 1, a significant condition by time interaction
(p < 0.01), time main effect (p < 0.01), and condition main effect
(p < 0.01) was observed for quadriceps muscle thickness. Follow-
up analyses revealed that quadriceps muscle thickness was signifi-
cantly greater for LI-BFR immediately post-exercise (p < 0.01) and
30 min post-exercise (p = 0.01) in comparison to pre-exercise meas-
ures. For the HI condition, quadriceps muscle thickness was signif-
icantly greater immediately post-exercise (p = 0.01), 30 min post-

Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
 ▶table 3 Hematocrit values expressed as percent of blood volume and
plasma volume percent changes expressed relative to baseline values.
1.5

Condition
LI-BFR (n = 10) HI (n = 10) CON (n = 10)
Hamstrings thickness (cm)

1.0
Hematocrit ( %):
Pre-Exercise 41.4 ± 3.7 42.5 ± 3.6 41.4 ± 3.2
0.5
Im Post-Ex 44.7 ± 3.5 * † 45.5 ± 3.2 * † 41.9 ± 2.7
60 min Post-Ex 41.9 ± 3.8 43.0 ± 3.5 41.3 ± 2.6

0.0 %∆PV:
Pre-Exercise N/A N/A N/A
Im Post-Ex − 12.3 ± 5.7 * † − 11.6 ± 5.9 * † − 2.1 ± 5.8
– 0.5
0 min 30 min 60 min 60 min Post-Ex − 1.7 ± 8.0 − 3.1 ± 5.8 0.5 ± 5.3
LI-BFR HI CON LI-BFR: Low-Intensity Resistance Exercise with Blood Flow Restriction.
TRE: Traditional Resistance Exercise. CON: Non-exercise con-
trol. %∆PV: Plasma Volume percent change. * Significant change
▶Fig. 2 Hamstring muscle thickness at rest and post-exercise from Pre (p < 0.05). †Significantly greater than CON at respective
across each condition. LI-BFR: Low-Intensity Resistance Exercise with time point (p < 0.05). Values are ± SD
Blood Flow Restriction; HI: High-Intensity Resistance Exercise; CON:
Non-Exercise Control. * Significant increase from Pre (p < 0.05).
Values are mean absolute change ± 95 % confidence interval.

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†‡
1 000

800
exercise (p < 0.01), and 60 min post-exercise (p < 0.01), when com-
pared to pre-exercise. There was no significant change over time 600
mCSA (mm2)

for CON. There were no significant differences across conditions at

400 ‡
baseline. However, LI-BFR and HI were significantly greater than
CON immediately post (LI-BFR: p < 0.01, HI: p = 0.02) and 30 min 200

post-exercise (LI-BFR: p < 0.01, HI: p < 0.01). Additionally, LI-BFR 0

was significantly greater than HI immediately post-exercise
– 200
(p = 0.01).
As shown in ▶Fig. 2, only a significant time main effect (p < 0.01) 15 min 75 min 24 h 48 h 72 h 96 h

and a significant interaction between condition and time (p = 0.03) LI-BFR HI CON

were observed for hamstring muscle thickness. Further analyses

revealed that hamstring muscle thickness for LI-BFR was signifi-
cantly greater immediately post-exercise (p = 0.03) when compared
to baseline. Furthermore, no significant differences over time were
observed in CON or HI (p > 0.05).
Hematocrit and plasma volume
The percent of blood volume consisting of red blood cells (hema-
tocrit percent) across all conditions are presented in ▶table 3. Sig-
nificant time (p = 0.03) and condition (p = 0.03) main effects, and
a significant condition by time interaction (p < 0.01) were observed
for hematocrit percent. Hematocrit percent was significantly great-
er for both LI-BFR (p < 0.01) and HI (p < 0.01) conditions immedi-
ately post-exercise from pre-exercise. In the comparison across
conditions, both LI-BFR (p < 0.01) and HI (p < 0.01) were significant-
ly greater than CON immediately post-exercise only.
▶ table 3 also illustrates the change in percent plasma volume
( %ΔPV) across all conditions. Significant condition (p = 0.03) and
time (p < 0.01) main effects and a significant interaction between
time and condition were detected for %ΔPV (p < 0.01). Further anal-
ysis revealed a significant decrease in %∆PV from pre-to post-ex-
ercise in both LI-BFR (p < 0.01) and HI (p < 0.01) conditions. Moreo-
ver, LI-BFR (p < 0.01) and HI (p < 0.01) were significantly greater than
CON immediately post-exercise.
▶Fig. 3 Muscle cross-sectional area at rest and post-exercise across
each condition. BFR: Low-Intensity Resistance Exercise with Blood
Flow Restriction; HI: High-Intensity Resistance Exercise; CON: Non-
Exercise Control. * Significant increase from Pre (p < 0.05). †Signifi-
cant difference from LI-BFR to CON (p < 0.05). ‡ Significant difference
from HI to CON (p < 0.05). Values are mean absolute change ± 95 %
confidence interval.
Muscle cross-sectional area
▶ Fig. 3 illustrates thigh mCSA at 50 % femur site across all condi-
tions tested. Significant main effects for time (p < 0.01) and condi-
tion (p = 0.03), and a significant condition by time interaction
(p < 0.01) were observed. No differences were observed across con-
ditions at baseline (p > 0.05). For LI-BFR, mCSA was significantly
greater than baseline values at 15 min (p < 0.01) and 75 min
(p = 0.01) post-exercise. For HI, mCSA was significantly higher than
baseline at 15 min post-exercise (p < 0.01), but it returned to val-
ues similar to pre-exercise within 75`min (p > 0.05). No significant
differences over time were observed for CON (p > 0.01). No signifi-
cant differences were observed across conditions at baseline
(p > 0.05). However, LI-BFR and (p < 0.01) and HI (p < 0.01) were sig-
nificantly greater then CON at 15 min post-exercise. Likewise, HI
was significantly greater than CON at 48 h post-exercise hours
(p < 0.01).

Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
 Training & Testing
3 However, these exercise conditions were performed until volition-
†‡
2 compared to the high-intensity condition. An additional study by
Circumference (cm)
1
0 tion in the volume of the exercise. In the present study, none of the
–1
15 min 75 min 24 h 48 h 72 h
LI-BFR HI CON
▶ Fig. 4 Thigh circumference at rest and post-exercise across each
condition. BFR: Low-Intensity Resistance Exercise with Blood Flow
Restriction; HI: High-Intensity Resistance Exercise; CON: Non-Exer-
cise Control. * Significant increase from Pre (p < 0.05). †Significant
difference from LI-BFR to CON (p < 0.05). ‡ Significant difference from
HI to CON (p < 0.05). Values are mean absolute change ± 95 % confi-
dence interval.
Thigh circumference
Thigh circumference at 50 % femur site across conditions is pre-
sented in ▶ Fig. 4. There was a significant main effect for time
(p < 0.01) and a significant condition by time (p < 0.01) interaction
for thigh circumference. No significant differences were observed
across conditions at baseline (p > 0.05). Follow-up analyses revealed
that all conditions were significantly greater than their respective
pre-exercise values at 15 min post-exercise (p < 0.01). Thigh cir-
cumference was significantly greater in LI-BFR (p = 0.03) and HI
(p < 0.01) at 75 min post-exercise when compared to their respec-
tive baseline values. Additionally, LI-BFR (p = 0.03) and HI (p < 0.01)
were significantly great than CON at 75 min post-exercise.
Discussion
This study aimed to investigate the time course changes in intra-
muscular fluid by looking at changes in plasma volume and muscle
swelling post-acute bouts of high-intensity resistance exercise and
low-intensity exercise with BFR. To the best of our knowledge, this
was the first study to investigate prolonged time course changes
in muscle swelling and plasma volume following BFR exercise up to
96 h post-exercise. The findings of this study partially confirm our
previous hypothesis that BFR exercise would induce a significant
increase in muscle swelling and a significant decrease in plasma
value; however, these responses were similar between both high-
intensity (80 % of 1RM) and low-intensity resistance exercise (20 %
of 1RM) with BFR.
Our results are consistent with previous literature, which has
also observed significant acute increases in muscle swelling post
resistance exercise with or without BFR [23]. Interestingly, Jenkins
et al. [16] observed that low-intensity resistance exercise at 30 %
of 1 RM caused greater acute muscle swelling immediately post-
Thieme
exercise in comparison to resistance exercise at the 80 % of 1RM.
al fatigue without BFR, which caused the low-intensity exercise
condition to present a larger exercise volume and total work done
Yasuda et al. [49] also performed the exercise to volitional fatigue,
but at the same low-intensity and it was observed that both exer-
cise conditions induced muscle swelling and decreased plasma vol-
ume; however, the application of BFR leads to a significant reduc-
exercise conditions were performed to fatigue and the execution
of resistance exercise with BFR induced acute responses similar to
96 h those observed at high-intensity with no BFR. Muscle swelling in-
duced by traditional high-intensity resistance exercise is due, in
part, to the muscle damage from this exercise modality [32]. On
the other hand, low-intensity BFR exercise has not been shown to
induce either acute or prolonged muscle damage [25, 43] or in-
flammation [1, 17, 18], regardless of the amount of pressure ap-
plied during exercise (unpublished data). The present study ob-
Downloaded by: University of Michigan. Copyrighted material.
served an acute increase in muscle swelling at 15 min post-exercise
measured by both ultrasound and pQCT, and at 30 min measured
by ultrasound. It is very likely that this early onset of muscle swell-
ing post-exercise was due to venous pooling. However, the accu-
mulation of metabolites inside the muscle caused by BFR may also
have induced a fluid shift from the extracellular to the intracellular
space, which could also have contributed to some extent, the ob-
served increased muscle swelling response. Nonetheless, a direct
measurement such as muscle biopsy is required to conform this
hypothesis and to examine what is happening at the cellular level.
Additionally, previous studies have demonstrated that the ap-
plication of BFR in the absence of exercise is effective at attenuat-
ing both muscle atrophy and muscle strength decreases as the re-
sult of limb immobilization [20, 21, 42]. Therefore, since we ob-
served that BFR exercise induced muscle swelling up to 75 min
post-exercise, these findings seem to support the previous hypoth-
esis that an increased muscle swelling response observed with BFR
exercise may stimulate hypertrophic response normally observed
with this training modality [22]. Other possibilities for the hyper-
trophic response include an increased muscle activation [47, 48]
and elevated anabolic hormone levels both systemically and local-
ly at the exercise site [28, 34, 40]. In this regard, Loenneke et al. [23]
investigated the effects of applying BFR in the absence of exercise
on muscle swelling, muscle activation, plasma volume, and lactate
production. The authors observed that the application of BFR with-
out exercise caused an acute increase in muscle swelling and an
acute decrease in plasma volume; there were no changes observed
in muscle activation and whole blood lactate. Muscle activation has
been shown to be increased with BFR exercise due to an early fa-
tigue of the slow-twitch muscle fibers and an early recruitment of
fast-twitch muscle fibers because of an increased sympathetic re-
sponse and increase in norepinephrine, which stimulates adrener-
gic B2 receptors, and results in a selective hypertrophy of the type
II fibers. In the case of lactate, it is believed that the buildup of hy-
drogen ions initiates a cascade of events that ultimately upregu-
lates anabolic hormones secretion, such as testosterone, GH, and
IGF-1. Therefore, the findings of Loenneke et al. [23] indicate that
Freitas EDS et al. Muscle Swelling Response To BFR Exercise … Int J Sports Med
the atrophy attenuating response observed in previous studies [3]
[20, 21, 42] might be due to the increased muscle swelling.
The present study also observed that the mCSA measured by
pQCT returned to baseline values within 75 min post-exercise. Pe-
[4]
ripheral QCT has been demonstrated to be a very valid and reliable
method to assess mCSA when compared with the gold standard
magnetic resonance imaging (MRI) [9], and the use of pQCT has
become a major method of assessing changes in both bone and
Ahtiainen JP, Pakarinen A, Alen M, Kraemer WJ, Häkkinen K. Muscle
hypertrophy, hormonal adaptations and strength development during
strength training in strength-trained and untrained men. Eur J Appl
Physiol 2003; 89: 555–563
ASCM.Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith
BK.ASCM. American College of Sports Medicine Position Stand.
Appropriate physical activity intervention strategies for weight loss
and prevention of weight regain for adults. Med Sci Sports Exerc 2009;
41: 459–471

soft tissues. Since BFR training has been shown to induce muscle
hypertrophy earlier than previously thought [1, 2], pQCT could be
used to assess muscle hypertrophy as early as 24 h post-exercise
without the problem of tissue swelling due to fluid shifts into the
muscle, since this study showed that the swelling disappears be-
fore 24 h post-exercise.
The present study has several limitations that warrant discus-
sion. One issue was that no female participants were included and
a standard pressure of 160 mmHg was used to restrict blood flow,
regardless of limb size. Even though these methods have been
largely applied throughout the literature, recent evidence suggest
[5] Van Beaumont W. Evaluation of hemoconcentration from hematocrit
measurements. J Appl Physiol 1972; 32: 712–713
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Downloaded by: University of Michigan. Copyrighted material.

that the pressure should be individually determined for each par-
ticipant [10]. Additionally, there was no direct assessment of mus-
cular tissue in the current study; thus, without this measurement
we can only speculate what happens at the cellular level.
Conclusion
In conclusion, an acute bout of low-intensity resistance exercise
(20 % 1RM) with BFR is capable of inducing acute muscle swelling
and acute decreases in plasma volume post-exercise to the same
extent as observed with traditional high-intensity resistance exer-
cise (80 % 1RM) with no BFR, however, these responses return to
baseline within 24 h post-exercise. Future studies should investi-
gate the impact of different levels of BFR pressures on muscle swell-
ing and plasma volume changes and perform direct tissue meas-
urements in order to determine the cellular physiological adapta-
tions within the muscle.
Funding
Financial support was provided by the office of the vice president
of research of the University of Oklahoma.
Conflicts of interest
The authors have no conflict of interest to declare.
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