Acta Physiologica Hungarica, Volume 101 (2), pp. 158–166 (2014) DOI: 10.1556/APhysiol.101.2014.2.4

Blood flow restriction: Effects of cuff type on fatigue and perceptual responses to resistance exercise JP Loenneke1, RS Thiebaud1, CA Fahs1, LM Rossow1, T Abe2, MG Bemben1 1

Department of Health and Exercise Science, Neuromuscular Research Laboratory, The University of Oklahoma, Norman, OK, USA 2 Department of Health, Exercise Science, and Recreation Management, University of Mississippi, Oxford, MS, USA Received: January 21, 2013 Accepted after revision: June 17, 2013 Blood flow restriction (BFR) combined with low load resistance training has been shown to result in muscle hypertrophy similar to that observed with higher loads. However, not all studies have found BFR efficacious, possibly due to methodological differences. It is presently unclear whether there are differences between cuffs of similar size (5 cm) but different material (nylon vs. elastic). The purpose was to determine if there are differences in repetitions to fatigue and perceptual ratings of exertion (RPE) and discomfort between narrow elastic and narrow nylon cuffs. Sixteen males and females completed three sets of BFR knee extension exercise in a randomized crossover design using either elastic or nylon restrictive cuffs applied at the proximal thigh. There were no differences in repetitions to fatigue (marker of blood flow) or perceptual ratings between narrow elastic and narrow nylon cuffs. This data suggests that either elastic or nylon cuffs of the same width should cause similar degrees of BFR at the same pressure during resistance exercise. Keywords: KAATSU, failure, occlusion, skeletal muscle

Blood flow restriction (BFR) by itself or in combination with exercise has been shown to be beneficial for skeletal muscle (9). In addition, when BFR is combined with low load resistance training, it has been shown to result in similar muscular adaptations as higher load exercise (8) through a variety of proposed mechanisms such as muscle cell swelling and metabolicinduced fiber type recruitment (9). Recently, Nielsen et al. (17) presented research that suggests that the proliferation of myogenic stem cells may be an additional mechanism involved in the muscle hypertrophic response to high-frequency low load resistance exercise with BFR. The increased proliferation of myogenic stem cells with resistance training in combination with BFR is significant as it is thought that the myonuclear donation may be required in order to substantially increase muscle fiber cross-sectional area (18) although not all evidence supports this hypothesis (15). Despite most of the BFR literature being overwhelmingly positive, not all studies show a beneficial effect of BFR exercise compared to regular exercise without BFR (1). Some of the discrepancy can be explained by differences in methodology. For example, a recent study highlighted the importance of reporting cuff size after demonstrating that wide (13.5 cm) nylon cuffs result in arterial occlusion at a much lower pressure than narrow elastic (5 cm) cuffs (11). In addition, these narrow elastic cuffs are regulated by the Kaatsu Master which

Corresponding author: Jeremy Paul Loenneke 1401 Asp Avenue, Room 104, Norman, OK, 73019-0615, USA Phone: +1-405-325-5211; Fax: +1-405-325-0594; E-mail: [email protected] 0231–424X/$ 20.00 © 2014 Akadémiai Kiadó, Budapest

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can determine the initial pressure (pressure the cuff is applying to the limb prior to inflation) and different initial pressures have resulted in differing acute responses to BFR (7). However, although it is evident that there are differences in the degree of BFR between elastic narrow (5 cm) cuffs and nylon wide (13.5 cm) cuffs (11, 20), it is presently unclear whether or not there are differences in BFR between two cuffs of similar size (5 cm) but different material (nylon vs. elastic) during exercise. We recently demonstrated that cuffs of similar size but different material resulted in similar arterial occlusion pressures during supine rest (13), however, differences between the cuffs may only become evident during upright resistance exercise. This study is important because not every facility has access to the 5 cm specialized “Kaatsu” elastic cuffs and have therefore relied on using different pneumatic cuff systems (e.g. E-20 rapid cuff inflator) which are primarily used for cardiovascular measurements. If there are no significant differences between the nylon and elastic cuffs then this technique might be able to be more widely studied. However, if there are meaningful differences, then researchers using cuffs of similar size but different material may not be able to directly compare results across studies. We hypothesized that although the two cuffs are of similar size there would be significant differences in repetitions to fatigue between the two cuffs because of the inability to set the initial pressure with the narrow (5 cm) nylon cuffs. In addition, we conducted a secondary exploratory analysis to determine if sex differences exist for repetitions to fatigue. Due to the difficulty of directly measuring changes in blood flow with ultrasound during exercise, we chose to measure repetitions to fatigue as a surrogate marker of changes in blood flow (19). Materials and Methods Participants A total of seventeen recreationally active males (n = 8) and females (n = 9) were recruited to participate in the current study. Participants were excluded if they were pregnant, hypertensive (brachial pressure > 140/90 mmHg), or had an ankle brachial index (ABI) of less than 0.9. Further exclusion criteria included having more than one risk factor for thromboembolism which include the following: 1) obesity (BMI ≥ 30 kg/m2), 2) diagnosed Crohn or inflammatory bowel disease, 3) a past fracture of a hip, pelvis, or femur, 4) major surgery within the last 6 months, 5) varicose veins or, 6) a family history of deep vein thrombosis or pulmonary embolism (16). One male participant completed paper work but did not return for Visit 1; therefore, his data was excluded from all analyses leaving a final sample size of 16 (Table I). For Visit 1, all participants were tested at least two hours post-prandial and were instructed to avoid caffeine, medications, and exercise for the 24-hour period prior to their first visit. For Visits 2 and 3, participants were asked to refrain from strenuous exercise 48 hours prior to coming in for testing. The study received approval from the university’s institutional review board, and participants were thoroughly informed of the purpose, nature, practical details and possible risks associated with the experiment, as well as the right to terminate participation at will, before they gave their voluntary informed consent to participate. Experimental design The participants visited the laboratory on three separate occasions. The first visit included measurements of blood pressure, thigh circumference, strength, and a familiarization with Acta Physiologica Hungarica 101, 2014

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Table I. Descriptive data of the participants in the study Mean (n = 16) Age (yrs)

Min–Max

24 (3)

19–29

Height (m)

1.70 (0.10)

1.53–1.86

Body Mass (kg)

72.1 (17.9)

50.2–102.1

Circumference (cm)

58.9 (4.6)

52.0–68.5

90 (34)

45–142

1RM (kg)

1RM: one repetition maximum; Variability represented as standard deviations (SD)

the exercise cadence. Following Visit 1, in a randomized cross-over design, participants completed knee extension exercise to fatigue wearing either elastic or nylon cuffs (Visit 2). A minimum of 5 days later, participants reported back for Visit 3 where they completed knee extension exercise to fatigue wearing the cuffs not worn during Visit 2. The cuffs worn during exercise were either elastic (5 cm wide × 135 cm long) or nylon (5 cm wide × 83 cm long) and were placed at the most proximal portion of each leg and the cuffs were inflated and deflated until reaching their target pressure. Once the target pressure was reached, the cuffs were inflated and participants then completed 3 sets of dynamic knee extension exercise to volitional fatigue with 30 seconds rest between each set. The exercise was completed at a metronome controlled pace of 1.5 seconds for the concentric portion and 1.5 seconds for the eccentric portion of the lift at 30% of their concentric one repetition maximum (1RM). The participants were instructed to exercise until volitional fatigue or until they were unable to complete the repetition through a full range of motion or maintain the exercise cadence. In addition, prior to knee extension exercise and following each set of exercise, ratings of perceived exertion (RPE) and discomfort were taken to quantify the perceptual differences between the stimuli. The data from Visit 2 and Visit 3 were recorded on separate sheets to ensure that the researcher was blinded to the number of repetitions and perceptual responses from the previous visit. Also, the participants were blinded from Visit 2 to Visit 3 by not being told how many repetitions they completed during Visit 2. Systolic and diastolic blood pressure Brachial systolic (bSBP) and diastolic (bDBP) blood pressure was measured using an appropriate sized automatic blood pressure cuff (Omron, Model HEM-773). Blood pressure was taken in duplicate and averaged. Ankle brachial index (ABI) The ABI is a ratio of the blood pressure in the lower legs to the blood pressure in the arms and was used to detect peripheral vascular disease. With the participant supine, the bSBP was obtained in each arm using a hand-held bidirectional Doppler (MD4, Hokanson, Bellevue, WA) probe placed on the artery at an angle of 45–60 degrees. A MV10 segmental cuff attached to a manual handheld cuff inflator (Hokanson, Bellevue, WA) was placed proximal to the Doppler probe and inflated on the limb to a supra-systolic pressure and then slowly deflated until a pulse (arterial flow) was detected. Ankle blood pressure (ABP) was measured at the posterior tibial artery using the same procedure. The ABI was calculated by dividing ABP by the higher of the two brachial pressures. Peripheral vascular disease is indicated by an ABI of < 0.9. All participants had an ABI > 0.9. Acta Physiologica Hungarica 101, 2014

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Thigh circumference The distance from the inguinal crease to the top of the patella was measured using a tape measure and a mark was made on the leg 33% distal to the inguinal crease. Thigh circumference was measured at this mark to capture an accurate representation of the site at which the cuffs would be applied. One repetition maximum (1RM) Participants’ bilateral knee extensor strength was tested using a seated knee extension machine (Cybex Strength Systems,Medway, MA, USA). The participants were instructed to perform 4–6 repetitions bilaterally for each leg (estimated ~50–60% 1RM). Following a rest of 60 seconds, the weight was increased again and participants were instructed to perform 2 bilateral repetitions (estimated ~70–80% 1RM). Following the two warm ups, the weight was progressively increased until the 1RM was determined. All 1RM’s were achieved within 5 attempts. 1RM was defined as the most weight that could be lifted through a controlled, full range of motion (ROM). Full ROM was visually defined as completing a repetition from the starting angle of 90˚ to a full lockout at 180˚. Perceptual responses Participants’ received verbal instructions on rating RPE and discomfort on the second and third visit, similar to those used by Hollander et al. (6). For RPE, participants were told, “We want you to rate your perception of exertion, that is, how heavy and strenuous the exercise feels to you. The perception of exertion depends mainly on the strain and fatigue in your muscles. We want you to use this scale from 6–20 and, where 6 means ‘no exertion at all’ and 20 means ‘maximal exertion’; any questions?” Participants fully understood how to rate RPE prior to actual testing. RPE was taken prior to exercise and after each set (4 time points). A rating of discomfort was taken using Borg’s Discomfort scale (CR-10+). Participants were asked, “What are your worst experiences of discomfort? ‘Maximum discomfort (rating of 10)’ is your main point of reference; it is anchored by your previously experienced worst discomfort. The worst discomfort that you have ever experienced, the ‘Maximum discomfort’ may not be the highest possible level of discomfort. There may be a level of discomfort that is still stronger than your 10; if this is the case, you will say 11 or 12. If the discomfort is much stronger, for example, 1.5 times ‘Maximum Discomfort’ you will say 15; any questions?” Participants fully understood how to rate discomfort prior to actual testing. A  rating of discomfort was taken prior to exercise and after each set of exercise (4 time points). Blood flow restriction (BFR) Participants wore either elastic (5 cm wide, 135 cm long, Kaatsu-Master, Tokyo, Japan) or nylon (5 cm wide, 83 cm long, Hokanson, SC5, Bellevue, WA, USA) cuffs around the most proximal portion of each leg. The elastic cuffs were applied with an initial compressive force of 50 mmHg (7). The nylon cuffs were applied tightly around the upper thigh; however, the device which inflates the nylon cuffs does not allow an initial compressive force to be set. The elastic cuffs were connected to a Kaatsu-Master Cuff inflator (Sato Sports Plaza, Tokyo, Japan); the nylon cuffs were connected to an E 20 Rapid Cuff Inflator (Hokanson, Bellevue, WA, USA). Both devices adjust cuff pressure automatically and actual cuff pressures were confirmed on the machines’ digital window. The same inflation protocol was used for both types of cuffs. Initial cuff pressure was set to 50 mmHg. Cuffs were then inflated to the Acta Physiologica Hungarica 101, 2014

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participant’s bSBP for 30s and then released for 10s. This 30s inflation / 10s deflation process was performed in increasing increments of 20 mmHg until the target pressure was reached. This protocol is used to slowly introduce the restriction pressure to participants, rather than going directly to the target pressure. Using previous data which suggests thigh circumference as the biggest predictor of arterial occlusion pressure during supine rest [(11), n = 116], we plotted thigh circumference against arterial occlusion to determine a relative sub-occlusion exercise pressure for each participant (i.e. < 45–50 cm = 120 mmHg; 51–55 cm = 150 mmHg; 56–59 cm = 180 mmHg; and ≥ 60 cm = 210 mmHg). This would ensure that the inflated cuff pressure was individualized to the person and would not cause arterial occlusion during upright exercise. Statistical analyses All data were analyzed using the SPSS 18.0 statistical software package (SPSS Inc., Chicago, IL, USA) with variability represented as standard deviation (SD). A two (cuff) by three (time) repeated measures analysis of variance (ANOVA) was used to determine differences in repetitions across time. If significance was found, a paired sample t-test with a Bonferroni corrected alpha was used to determine where the difference existed. To compare differences in the perceptual responses (RPE and Discomfort), the Wilcoxon related samples nonparametric test was used to determine if significant differences existed between conditions at different time points (Pre vs. Pre, 1st set vs. 1st set, 2nd set vs. 2nd set, and 3rd set vs. 3rd set). Spearman’s rho was used to determine if there was a relationship between the absolute pressure applied and the percent drop in repetitions from the first to the third set of exercise. A secondary exploratory analysis using a two (cuff) by three (time) repeated measures ANOVA with sex as a between subject factor was used to determine possible sex differences in repetitions to fatigue. Statistical significance was set at an alpha level of 0.05. Results No significant (p = 0.198) overall difference was found between cuff types for the average number of repetitions performed per set [elastic 14 (3) vs. nylon 13 (3) repetitions; d = 0.33]. With respect to changes in the number of repetitions completed, there was a significant (p < 0.01) time effect, with repetitions decreasing across sets (1st set > 2nd set > 3rd set, Fig. 1). There were no significant correlations between the BFR pressure applied and the percent drop in repetitions from the 1st set to the 3rd set for either the elastic (rho = –0.078, p = 0.773) or nylon (rho = –0.052, p = 0.849) cuffs, suggesting that the absolute pressure was not driving the decrease in repetitions. In addition, no significant differences were found between cuff types for RPE (all time points had a p ≥ 0.317) or ratings of discomfort (all time points had a p ≥ 0.296, Table II). A secondary exploratory analysis between sex on repetitions to fatigue did not find a significant overall cuff difference [elastic 13 (3) vs. nylon 13 (3) repetitions; d = 0.00, p = 0.216], sex difference (p = 0.295), cuff × time × sex interaction (p = 0.115), cuff × sex (p = 0.957) interaction, or a sex × time (p = 0.823) interaction. The only significant (all time points had a p ≤ 0.012) finding was a main effect for time (1st set > 2nd set > 3rd set). Mean differences (male mean–female mean) between the total repetitions completed found that on average males completed fewer repetitions than females for both the elastic (–1 repetitions) and nylon (–1 repetitions) cuffs. However, the difference between sexes appears to visually increase as Acta Physiologica Hungarica 101, 2014

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the duration of exercise increases (~3 repetitions difference for the third set, Fig. 2). Finally, the most commonly applied pressure was 210 mmHg (n = 4) and 150 mmHg (n = 4), for males (ranged from 180–210 mmHg) and females (ranged from 150–210 mmHg), respectively.

Fig. 1. The mean number of repetitions completed separated out by cuff type (elastic vs. nylon). Variability represented as standard deviations (SD)

Table II. Percentile (25th, 50th and 75th) ratings of perceived exertion (RPE) and discomfort representing each set of exercise for both cuff types (elastic vs. nylon) Elastic cuffs

25th

50th

75th

Nylon cuffs

25th

50th

75th

RPE at rest

6

6

6

RPE at rest

6

6

6

Set 1

13

16

17

Set 1

15

15

17

Set 2

15

17

18

Set 2

16

17

19

Set 3

15

18

19

Set 3

16

18

19

Discomfort at rest

0

0

0

Discomfort at rest

0

0

0

Set 1

3

4

7

Set 1

3

5

7

Set 2

4

7

8

Set 2

5

6

8

Set 3

5

7

9

Set 3

6

7

9

Discussion Contrary to our hypothesis, there were no significant differences between cuff types with respect to repetitions to fatigue (Fig. 1). We hypothesized that, although they would be inflated to the same pressure, there would be differences in blood flow between the cuffs due to the inability to set the “initial pressure” with the nylon cuffs. Therefore, this study suggests that setting the initial pressure may not be as important with less stretchable nylon cuffs. In addition, there were no significant differences in RPE or ratings of discomfort between cuff types (Table II). A secondary purpose of the study was to explore the possibility of a sex Acta Physiologica Hungarica 101, 2014

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difference with respect to repetitions to fatigue. Although our study found no statistical difference, descriptively, mean and percentile differences between sexes may begin to become apparent towards the end (~3rd set to fatigue) of exercise (Fig. 2 and Table III).

Fig. 2. The mean number of repetitions completed separated out by sex and cuff type (elastic vs. nylon). M-Elastic: male elastic; M-Nylon: male nylon; F-Elastic: female elastic; and F-Nylon: female nylon. Variability represented as standard deviations (SD)

Table III. Percentile (25th, 50th and 75th) differences in the number of repetitions completed separated out by sex and cuff type (elastic vs. nylon) Elastic cuffs

25th

50th

75th

Male set 1

22

23

30

Set 2

7

9

10

Set 3

3

6

Female set 1

21

Set 2

6

Set 3

7

Nylon cuffs

25th

50th

75th

Male set 1

21

22

33

Set 2

4

8

8

7

Set 3

2

6

8

25

31

Female set 1

21

23

32

8

13

Set 2

7

8

13

7

10

Set 3

6

7

9

Methodologically this data may have important implications for the study of BFR in combination with resistance exercise. Prior to this investigation, it was known that differences in cuff width resulted in marked differences in blood flow; however, it was unknown if cuff material (elastic vs. nylon) also affected the response during exercise. The results of this study found no difference in repetitions to fatigue between cuff types, suggesting the possibility that narrow nylon cuffs regulated by the E-20 rapid cuff inflator (Hokanson) device produce a similar response as the elastic cuffs regulated by the Kaatsu-Master device. There was a 72% and 74% reduction in repetitions from the first set to the third set for the elastic and nylon cuffs, respectively. This large drop in repetitions has been observed previously, and is attributed to transient muscle fatigue, not muscle damage (12). Although Acta Physiologica Hungarica 101, 2014

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not measured in the present investigation, muscle fatigue may have been due to an increase in intramuscular inorganic phosphate concentration, as this has been previously observed to occur following resistance exercise in combination with BFR (21). These findings suggest that the muscle fatigue with the elastic and nylon cuffs may have been due to a decline in the amplitude of the calcium transient and an inhibition of the cross-bridge cycle (4). This increased fatigability with the application of BFR in combination with resistance exercise is thought to provide at least part of the mechanistic rationale for inducing skeletal muscle hypertrophy (14). The perceptual responses (Table II) to BFR in combination with resistance exercise were not different between the elastic and nylon cuffs. The 50th percentile for both cuffs resulted in a rating of 18 (Very Hard–Extremely Hard Exertion) for RPE and 7 (Very Strong Discomfort) for ratings of discomfort following the final set of resistance exercise. These high ratings are similar to what has been observed previously with low load resistance exercise in combination with BFR (10, 12). The elevated perceptual responses with BFR in combination with resistance exercise despite the low load used, is in response to the elevated intramuscular intensity from the application of BFR (12). When separating by sex, there were no statistical differences with repetitions to fatigue. However, when investigating the means, medians, and the 25th and 75th percentiles across exercising sets (Fig. 2 and Table III), the data collectively suggests that females may be completing more repetitions than males as exercise duration increases. This is currently speculation and should be interpreted cautiously, but a potential explanation may be due to differences in exercise load; because males exercised with a much higher load (males = 37 kg vs. females = 19 kg) in the present investigation. It has been previously shown that greater loads are associated with a greater increase in intramuscular pressure, which can increase fatigue by reducing blood flow and subsequently increasing metabolic accumulation (5). On the surface this may seem to contradict Clark et al. (2) who have found that sex differences are eliminated when blood flow is completely occluded. However, the current mode of exercise does not result in arterial occlusion. Instead, the goal of BFR in combination with resistance exercise is to occlude venous flow from the muscle while only restricting arterial flow into the muscle. We chose to perform this investigation on the lower body because the majority of BFR studies have utilized lower body BFR exercise training (3). Consequently, these findings cannot necessarily be applied to upper body resistance exercise. In addition, we assessed changes in blood flow based on repetitions to fatigue in this study; therefore, we suggest that future studies directly quantify the amount of blood flow restriction between cuff types. In conclusion, there were no differences in repetitions to fatigue (a marker of blood flow) between narrow elastic and narrow nylon cuffs. In addition, the perceptual response to fatiguing exercise between cuffs was similar. These data suggests that either elastic or nylon cuffs of the same width should cause similar degrees of BFR at the same pressure during resistance exercise. Future research is needed to further explore potential sex differences that may become more apparent with increasing exercise duration. Funding Sources The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this manuscript. This study was not supported by any funding.

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Conflict of Interest None of the authors report a conflict of interest.

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Blood flow restriction: effects of cuff type on fatigue and perceptual responses to resistance exercise.

Blood flow restriction (BFR) combined with low load resistance training has been shown to result in muscle hypertrophy similar to that observed with h...
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