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Original Investigations

Effects of Exercise Load and Blood-Flow


Restriction on Skeletal Muscle Function
SUMMER B. COOK, BRIAN C. CLARK, and LORI L. PLOUTZ-SNYDER
Musculoskeletal Research Laboratory, Department of Exercise Science, Syracuse University, Syracuse, NY

ABSTRACT
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COOK, S. B., B. C. CLARK, and L. L. PLOUTZ-SNYDER. Effects of Exercise Load and Blood-Flow Restriction on Skeletal Muscle
Function. Med. Sci. Sports Exerc., Vol. 39, No. 10, pp. 1708–1713, 2007. Resistance training at low loads with blood flow restriction
(BFR) (also known as Kaatsu) has been shown to stimulate increases in muscle size and strength. It is unclear how occlusion pressure,
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exercise intensity, and occlusion duration interact, or which combination of these factors results in the most potent muscle stimulus.
Purpose: To determine the effect of eight BFR protocols on muscle fatigue (decrement in maximal voluntary contraction (MVC) after
the performance of exercise), and to compare the decrement in MVC with the currently recommended resistance exercise intensity
(~80% MVC). Methods: During five test sessions, 21 subjects (14 males and 7 females, 27.7 T 4.9 yr) completed nine protocols, each
consisting of three sets of knee extensions (KE) to failure. One protocol was high-load (HL) exercise (80% MVC) with no BFR, and
the other eight were BFR at varying levels of contraction intensity (20 or 40% MVC), occlusion pressure (partial (~160 mm Hg) or
complete (~300 mm Hg)), and occlusion duration (off during the rest between sets or continuously applied). To evaluate each protocol,
MVC were performed before and after exercise, and the decrement in force was calculated. Results: Three sets of KE at 20% MVC
with continuous partial occlusion (20%ConPar) resulted in a greater decrement in MVC compared with HL (31 vs 19%, P = 0.001).
None of the other BFR protocols were different from the HL protocol, nor were they different from 20%ConPar (P > 0.05). Conclusion:
All BFR protocols elicited at least as much fatigue as HL, even though lower loads were used. The 20%ConPar protocol was the only one
that elicited significantly more fatigue than HL. Future research should evaluate protocol training effectiveness and overall safety of
BFR exercise. Key Words: ISCHEMIA, KAATSU, QUADRICEPS, FATIGUE, EXERCISE PROTOCOLS

T
he American College of Sports Medicine (ACSM) mechanical stress (10), endocrine responses (12), and
recommends resistance training at moderate to high metabolite accumulation (10). For example, large, acute
loads (70–85% of one-repetition maximum (RM)) increases in growth hormone (GH) immediately after HL
using multiple sets of 8–12 repetitions with short rest exercise is theorized to stimulate the secretion of insulin-
periods (1–2 min) two to three times per week (3). like growth factors (IGFs) leading to increased protein
Resistance training regimens that use the principles of synthesis and ultimately muscle hypertrophy (3,12).
progressive overload are likely to result in increased muscle During periods of reduced muscle use, such as space-
size and, consequently, strength (3). Skeletal muscle flight and post-injury/surgery, substantial losses in muscle
responds to overload with enhanced rates of protein mass and strength are observed (18,24). Because perform-
synthesis leading to increases in the size and amount of ing HL resistance training during these times are not always
contractile proteins within each muscle fiber (20). Although feasible and at times actually contraindicated, it is plausible
the exact mechanisms that trigger protein synthesis remain that the benefits of HL exercise can be achieved using
elusive, muscle hypertrophy and increased strength as a considerably lower loads and blood flow restriction (BFR)
result of high-load (HL) resistance training is generally (also known as vascular occlusion or ischemia). Exercising
thought to be associated with the recruitment of higher with BFR is routinely performed in Japan where it is
threshold motor units (14) resulting in increases in referred to as Kaatsu. Researchers have reported similar
muscular adaptations in Kaatsu as seen in HL exercise, and
Address for correspondence: Summer B. Cook, M.S., Syracuse University
Department of Exercise Science, 820 Comstock Avenue, Room 201, sometimes in a more rapid time course (1,25,27). For
Syracuse, NY 13244-5040; E-mail: slbaldwi@syr.edu. example, Takarada et al. (25) report similar gains in
Submitted for publication March 2007. strength and muscle cross-sectional area (CSA) after 16
Accepted for publication May 2007. wk of either BFR or HL resistance training of the elbow
0195-9131/07/3910-1708/0 flexors, and Abe et al. (1) describe an almost 9% increase in
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ CSA accompanied by a 17% rise in squat strength after only
Copyright Ó 2007 by the American College of Sports Medicine 2 wk of training twice per day with a vascular occlusion at
DOI: 10.1249/mss.0b013e31812383d6 20% 1RM. They also found 20% higher serum insulin-like

1708

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
growth factor-1 (IGF-1) at the end of the 2 wk of training, pation in this study. All subjects signed an informed consent
attributing the rise in CSA and strength to increased protein approved by the Syracuse University Institutional Review
synthesis through the GH–IGF–1 axis (1). Comparable Board. Subjects completed a health questionnaire and
improvements in strength and IGF-1 levels have been anyone with a family history (including themselves) of
shown after 13 wk of HL training at 70% 1RM (5). In blood clotting disorders and individuals with orthopedic
addition to these chronic positive effects, our laboratory has injuries or limitations associated with the legs were
reported an acute ninefold increase in serum GH from excluded from the study. Additionally, subjects who
baseline to the cessation of an exercise bout consisting of reported using drugs that are known to increase the risk of
knee extensions at 20% maximum voluntary contraction circulatory problems (hormonal contraceptive medicine)
(MVC) with BFR (17), and others have reported GH were excluded. The subjects were 27 T 4.9 yr, had a mean
increases of up to 290 times baseline values (21,23,26,28), height of 1.73 T 0.07 m, and weighed 74.4 T 14.4 kg. All
with the GH responses following BFR exercise being subjects participated in some form of regular physical
similar to, or even high than those reported during HL activity (i.e., running, cycling, resistance training), but were
exercise of intensities at about 70% 1RM (11,19). asked to refrain from strenuous bouts of exercise for 2 d
When the long- and short-term effects of BFR exercise on before each testing session.
muscle and endocrine function are considered collectively, the
Experimental Design
data suggest that BFR exercise may indeed be a potent

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stimulator of muscle growth. However, since training with a The study required subjects to visit the laboratory on five
blood flow restriction is rather novel (since about 2000), little is separate occasions, with at least 5 d between visits. Subjects
known about the most effective BFR protocol regarding completed nine different exercise protocols, and the order of
exercise intensity and occlusion pressure and occlusion the protocols was counterbalanced. Each testing session
duration. Currently, studies using BFR vary greatly in terms involved the completion of two exercise protocols and
of the protocol employed. For instance, exercise loads have lasted approximately 1.5 h. Before testing, blood pressure
ranged from 20 to 50% of 1RM or MVC (1,6,16,17,21– was taken and used to determine occlusion pressure.
23,25–29), occlusion pressures have been moderate (about Strength testing. Isometric muscle strength was
30% above systolic blood pressure, or about 160 mm Hg) assessed before and immediately upon completion of each
(1,6,19,21,22,25) or high enough to completely restrict blood exercise protocol. To measure exerted force, subjects were
flow (~300 mm Hg) (8,16,17,26,27,30), and the occlusion seated in a knee extension dynamometer (MedX, Ocala,
duration is not often specified, thus making it unclear whether FL). The back rest was adjusted to create a hip joint angle
the pressure was constantly applied throughout rest periods or of 100- from flexion, and a seat belt was secured across the
released at the completion of each exercise set (25,27). If subject_s hips to reduce any movements of the hip joint, and
BFR exercise is to be developed as a viable intervention to to minimize assistance from other muscle groups. For MVC
enhance muscle mass and strength, understanding the inter- testing, the knee joint angle was set at 60- from extension.
play among these factors is critical in the development of the During testing the contralateral limb was extended and
most effective BFR exercise protocol. Therefore, the purpose rested on a pad. To obtain an MVC, subjects were instructed
of this study was to determine the acute effect of eight to push as hard as possible against an immovable arm
different BFR protocols on skeletal muscle fatigue (decrement attached to a force transducer. Isometric force was measured
in MVC immediately following the performance of exercise) by a force transducer (model U1T, HBM Inc., Marlborough,
and compare these changes with the currently recommended MA; sensitivity of 0.002 VIN-1), amplified and recorded at
resistance exercise intensity (~80% MVC) by the ACSM (3). 1000 Hz using a 16-bit data acquisition card (MP150,
On the basis of our previous finding that subjects who BioPac Systems Inc., CA). The force exerted by the subject
experienced the greatest decrement in force after a bout of was displayed on a 43-cm computer monitor located 1 m
BFR exercise concomitantly experienced the highest plasma directly in front of the subject. Subjects performed MVC
GH concentrations exercise (Spearman r = j0.69) (17), and before the exercise protocols until two consecutive trials
on the basis of the findings of Häkkinen and Pakarinen (9), were within 5% of each other, and the highest MVC
who report that the more fatiguing the exercise, the greater the obtained was used in the analysis. The day-to-day reliability
GH response, we suggest that in the present study, the most of the MVC using coefficient of variation was less than 8%.
fatiguing exercise protocol could reasonably be the most Subjects performed one MVC at the completion of the
potent stimulator for muscle growth and should be further exercise protocol, and this post strength was measured
tested in training studies. within 30 s after volitional fatigue. During all MVC, strong
verbal encouragement was given.
METHODS Exercise protocols. At each testing session subjects
performed two different exercise protocols (one with each
Subjects
leg) that involved three sets of dynamic knee extensions to
Twenty-one healthy, normotensive males and females volitional task failure. Before each protocol, the subject
were recruited from the university community for partici- performed a brief warm-up of 10–15 repetitions at a very

MUSCLE FUNCTION CHANGES WITH OCCLUSION Medicine & Science in Sports & Exercised 1709

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
light (less than 20% MVC) workload. Each set of knee P G 0.05. Statistics were computed using SPSS version 15.0
extensions was separated by a 90-s rest period, and (Chicago, IL).
completion of the two protocols was separated by
approximately 30 min of rest. The range of motion of the
RESULTS
exercise was between 12 and 108- of knee extension
(0- = full extension), and the subjects performed the leg MVC. Although males had higher initial MVC than
extensions at a fixed cadence (approximately a 2-s females (868.8 T 168.3 vs 550.8 T 61.0 N, P G 0.01, power =
concentric contraction and a 2-s eccentric contraction). 1.0, G2 = 0.55), the amount of fatigue (percent decrement
The BFR protocols included two different exercise in force) was similar across all protocols (P = 0.31, power =
intensities (20 or 40% MVC), two occlusion pressures 0.54, G2 = 0.06). Further gender comparisons were not
(partial (~160 mm Hg) or complete (~300 mm Hg)) and made because the fewer number of female subjects in the
two occlusion durations (no pressure during the rest sample substantially decreased the power of this analysis.
between sets or continuously applied). Each of these When the subjects repeated their first protocol on their
variables was independently manipulated resulting in a last visit, there were no differences in MVC (P = 0.89),
total of eight different protocols with an occlusion stimulus. force decrement (P = 0.82) and number of repetitions
An additional protocol was performed at 80% MVC with no performed (P = 0.17). Furthermore, there were no signifi-
BFR. The order of testing was counterbalanced and the leg cant differences between the subjects_ MVC over the nine
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tested on each protocol was randomly selected. On the fifth protocols (P = 0.91). This provides evidence that there was
testing session after all nine protocols were completed, each no training effect of the repeated testing.
subject repeated the first protocol they performed at the first Exercise loads. The average exercise load in the HL
testing session to ensure there was no training effect. was 609.3 T 170.8 N, whereas the LLO protocols at 20 and
The occlusion pressure was applied via a 6  83-cm 40% MVC exhibited loads of 161.1 T 50.4 and 304.2 T 85.0
tourniquet cuff (D.E. Hokanson, Inc., Bellevue, WA), N, respectively. All three exercise loads were significantly
placed at the most proximal position on the subject_s different from one another (P G 0.01).
thigh, and inflated (E20 Rapid Cuff Inflator, D.E. Hokanson, Repetitions. Subjects performed more repetitions
Inc., Bellevue, WA) to the designated pressure. In the during all BFR protocols when compared with HL (Table 1;
partial occlusion, the cuff was inflated to a pressure 30% P G 0.01, power = 1.0, G2 = 0.44). The number of
higher than the subject_s resting systolic blood pressure, and repetitions completed in the protocols at 20% MVC were
during the complete occlusion, pressure was set at 300 mm not different, regardless of occlusion pressure and duration
Hg. It has been suggested that a pressure 1.3 times systolic (mean = 165.0 T 108.9; P > 0.05). The number of
blood pressure (partial occlusion) impedes venous blood repetitions performed in the protocols at 40% MVC were
flow causing blood to pool in the capacitance vessels distal similar (mean = 83.8 T 43.4; P > 0.05) but were
to the cuff while restricting some arterial blood flow (25). significantly less than the 20% MVC protocols (P G 0.05).
Using Doppler ultrasound technology, our laboratory has Volume. Protocol volume (load  repetitions) was
previously confirmed that a pressure of 300 mm Hg results lowest in the HL protocol, and this was significantly lower
in blood flow cessation to the limb (7). in comparison with the 40% continuous partial occlusion
(40% ConPar ) and 40% intermittent venous occlusion
(40%IntPar) only.
Statistical Analysis
Fatigue. On the average, subjects experienced the least
Statistics are reported as means T standard deviations. amount of fatigue during the HL protocol (~19 T 12%)
Boxplots were used to display specific percentile points and and the highest during the 20% continuous complete
the overall shape of the data distribution. The central
horizontal line within each box is the median (50th
TABLE 1. Total repetitions completed during three sets of each protocol.
percentile) of the data. The top and bottom of each box
Protocol
displays the 25th and 75th percentiles while the ends of the
% MVC Pressure Duration Pressure Intensity Repetitions
whiskers are the 10th and 90th percentiles (29). One-way
HL 80 — — 33 T 10*
repeated-measures analysis of variance were used (within- 20%IntPar 20 Intermittent Partial 194 T 100
subject main effect: protocol) on the following variables: 20%IntCom 20 Intermittent Complete 143 T 75
20%ConPar 20 Continuous Partial 182 T 153
exercise load, repetitions, protocol volume (load  repeti- 20%ConCom 20 Continuous Complete 140 T 102
tions), force decrements, and force decrements per protocol 40%IntPar 40 Intermittent Partial 90 T 47†
volume. Post hoc comparisons were performed using the 40%IntCom 40 Intermittent Complete 84 T 37†
40%ConPar 40 Continuous Partial 83 T 32†
Bonferroni adjustment for multiple comparisons. Paired 40%ConCom 40 Continuous Complete 73 T 53†
t-tests comparing MVC, force decrement, and number of Data are displayed as means T SD.
repetitions on the protocol that each subject repeated were HL, high-load exercise; MVC, maximal voluntary contraction; int, intermittent; con,
continuous; par, partial; com, complete.
also done. Power and eta squared (G2) were reported as * Significant difference from all occlusion protocols (P G 0.05); † significant
appropriate, and significance was set at an alpha level of difference from all occlusion protocols at 20% MVC (P G 0.05).

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Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
FIGURE 1—Boxplot of percent force decrement (from MVC before and immediately after exercise) for each protocol. Protocol abbreviations are
listed in Table 1. The central horizontal line within each box is the median (50th percentile). The top and bottom of each box displays the 25th and
75th percentiles, and the ends of the whiskers are the 10th and 90th percentiles. Open circles represent individual outliers of 90th percentiles, and

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asterisks denote ‘‘far-out’’ outliers. A repeated-measures analysis of variance and Bonferroni adjustment for multiple comparisons post hoc test
reveal that 20%ConPar is significantly different from HL (P G 0.01).

(20%ConCom) and 20% continuous partial (20%ConPar) show that all acute bouts of exercise with BFR are as
occlusion protocols (33 T 18 and 32 T 12%, respectively). fatiguing or more fatiguing than a bout of HL exercise.
However, the only significant difference in fatigue among Whereas HL exercise resulted in a 19% decrement in
the nine protocols was between HL and 20% ConPar isometric force after a bout of exercise, BFR exercise showed
(P = 0.01, power = 0.91, G2 = 0.15). Although there was strength reductions of 24–33%. Häkkinen and Parkarinen (9)
a slightly greater decrement in force observed during report similar amounts of fatigue in that muscle force was
20%ConCom, this was not significantly different from HL reduced by 10.3 T 4.7 and 24.6 T 18.9% after two different
(P = 0.29), because of the greater variability associated with high-load protocols (20  1RM and 10 sets of 10 repetitions
the protocol. The boxplot (Fig. 1) reveals the data at 70% 1RM, respectively). Using a BFR protocol similar to
distribution associated with muscle fatigue. The 20%ConPar 20%ConCom but with a higher volume of exercise (five vs
protocol has the largest minimum fatigue value of all the three sets) being performed, Pierce et al. (17) have reported
protocols, indicating that subjects exhibited at least a 12% a 55.8% strength decrement. The magnitude of muscle
decrement in force, whereas other protocols resulted in fatigue after resistance exercise is known to be associated
small force decrements (20%IntPar = 2%, HL = 3%, and with the intensity of the exercise load, type of load (concen-
20%ConCom = 4%). Also, the 20%ConPar protocol has a small tric or eccentric muscle contractions), the rest intervals
spread (low variability) of values among the 25th and 75th between sets, and individual characteristics such as muscle
percentiles. The boxplots with the widest spread (most morphology and training status (9,13). In the present study, the
variability) are the 20%IntPar, 20%ConCom, 40%ConCom, and intensity of the load was the only factor that was manipulated,
40%IntPar protocols, respectively. and we have demonstrated that a bout of BFR exercise can be
Protocol efficiency. To evaluate the efficiency as effective as HL in generating muscle fatigue.
(whether more fatigue was induced using lower volumes Large increases in serum GH levels have been correlated
of exercise) of the protocols, fatigue was normalized to each with fatigue after single bouts of HL exercise (2,9), and GH
protocol volume (decrement in force/[load  repetitions]). is well-known to influence protein regulation and muscle
Although significant differences between protocols were growth during HL resistance training (11,12). We recently
found (P = 0.01), no significant pairwise comparisons were reported a relationship between acute fatigue and GH
evident using the Bonferroni adjustment for multiple secretion after nine subjects were observed under both
comparisons. The boxplot (not shown) exhibits similar BFR with resistance exercise and BFR without exercise
median values for force decrement per load in all protocols, (muscle ischemia without contraction) (17). Here, the
and all have similar spreads of values. ischemic condition alone resulted in a 16% decrement in
muscle force independent of a significant rise in GH, and
low-load exercise coupled with BFR resulted in a 55.8%
DISCUSSION reduction in muscle force accompanied by a ninefold
In this study, we sought to determine the most effective increase in GH levels. When the relationship between
combination of exercise load, occlusion intensity, and fatigue and GH response was evaluated using these data, a
occlusion duration to produce muscle fatigue. Our data significant correlation of j0.69 was evident, indicating that

MUSCLE FUNCTION CHANGES WITH OCCLUSION Medicine & Science in Sports & Exercised 1711

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
subjects who experienced the largest acute muscle fatigue situations in which a bloodless (via complete occlusion)
also had the highest plasma GH secretion (17). Therefore, operating field is needed, McEwen et al. (15) recommend
on the basis of these findings (17), we speculate that the using the minimum occlusion pressure possible to prevent
most fatiguing BRF exercise protocol in this study is the nerve, muscle, and skin injury. Although the long-term
most potent stimulator for muscle growth, as it would likely effects of BFR resistance training are unknown, other
elicit the greatest GH response. Although current studies authors have suggested that muscle and microvascular
reveal that BFR exercise results in muscle hypertrophy and damage may result from ischemia, including thrombus and
increased strength in as little as 2 wk (1,25,27,28), the pulmonary embolism formation (4,25). However, Takarada
muscular adaptations leading to hypertrophy remain et al. (26) found no evidence of muscle damage or oxidative
unknown. Additional training studies are warranted to stress when assessed by creatine phosphokinase and lipid
further establish the role of GH as a hypertrophic factor in peroxide, respectively, after a bout of exercise. Because
response to BFR exercise. there were no differences in fatigue among any of the BFR
Although there were no differences in the amounts of protocols tested in this study, we recommend using at most
fatigue exhibited among the BFR protocols, it is important a partial occlusion of 1.3 times systolic blood pressure
to determine which protocol would be best suited for a around the quadriceps femoris. With more research, it is
resistance training regimen. We evaluated several factors in possible that occlusion pressures less than that can
the BFR protocols, including degree of muscle fatigue, the effectively elicit muscle fatigue.
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range of fatigue within each protocol, fatigue variability, Although we did not take measurements of pain or
and protocol efficiency (force decrement per protocol discomfort associated with the exercise protocols, we
volume). On the basis of these criteria, at the present time anecdotally observed that 20%ConPar protocol was more
we recommend using the 20%ConPar protocol for several comfortable and tolerable than protocols with higher
reasons. First, this protocol was the only one that resulted in exercise loads and occlusion pressures. Wernbom et al.
a significantly greater decrement in force than HL (a (30) have reported pain ratings to be higher with BFR
decrease of 240 vs 140 N, or a 32% decrease in MVC vs exercise compared with a nonoccluded exercise at loads
a 19% decrease in MVC). Although 20%ConCom resulted in higher than 20% 1RM. They used a pressure of about 200
similar decrements as 20%ConPar, the subject variability in mm Hg, which is greater than the pressure used on
fatigue was much higher, making the impact of this protocol 20%ConPar. Therefore, although there were no differences
less predictable. Second, all subjects tended to respond to between the eight BFR protocols in the amount of fatigue
20%ConPar. For example, the minimum force decrement in exhibited, 20%ConPar seems to be a suitable protocol in
the 20%ConPar protocol was 64 N (or 12% MVC), whereas terms of comfort and effectiveness to induce muscle fatigue.
the minimum force decrements in the HL and 20%ConCom In conclusion, all BFR protocols elicited at least as much
protocols were 10 N (or 2% MVC) and 15 N (or 2.5% fatigue as HL, despite the fact that much lower loads were
MVC), respectively. Therefore, we expect that individuals used. The 20%ConPar protocol was the only one that elicited
would exhibit fatigue after 20%ConPar. Third, the variability significantly more fatigue than HL exercise and, therefore,
(as displayed by the spread of the boxes and the ends of the could have the potential to stimulate muscle growth. Future
whiskers in Fig. 1) is considerably uniform in 20%ConPar studies should include a comprehensive analysis of the
when compared with the other protocols. HL exercise is acute and long-term training adaptations and mechanisms
rather consistent, but, as stated previously, it exhibits much for hypertrophy from BFR resistance training and compare
lower force decrements than 20%ConPar. Fourth, although them to HL exercise training. The overall safety of BFR
more repetitions are performed during BFR, the exercise exercise needs to be evaluated as the effect of repeated,
volume (load  repetitions) is consistent in the 20%ConPar, regular bouts is unknown. Health risks associated with
20%ConCom, and HL protocols. Furthermore, the amount of long-term BFR training should be determined, and pop-
force decrement per exercise volume is the same in all ulations in which this type of training is contraindicated
protocols, indicating that although one may perform fewer should be established. Finally, the effectiveness of BFR
repetitions with HL, it is not more efficient in creating training for individuals who cannot engage in HL resistance
fatigue than an occlusion protocol. training (frail elderly, individuals postsurgery) should be
We also believe that 20%ConPar is more conservative (and further evaluated.
possibly safer) than several of the other BFR protocols,
because the occlusion pressure used is lower. Although This investigation was supported by the National Aeronautics
severe and often irreversible damage to skeletal muscle is and Space Administration (NASA) (NNX06AG26H).
Present address of B.C. Clark as of August 2006: Dept. of
believed to occur after a prolonged exposure to ischemia Biomedical Sciences, College of Osteopathic Medicine, Ohio Univ.,
(> 3 h) (4), each BFR protocol in this study was completed 211 Irvine Hall, Athens, OH 45701.
in less than 20 min, and no adverse effects of the exercise
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1712 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

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