Exercise training with blood flow restriction (BFR) utilizes low weight exercises while a pneumatic cuff surrounding the proximal end of the exercising limb (1) reduces arterial blood flow to and venous blood flow from the exercising muscle. This form of exercise is increasingly used as a means of eliciting hypertrophy and strength gains (2) with as little weight as 20% of a 1-repetition maximum (1RM) (3). Protocols for BFR have varied in the application of cuff pressures. Earlier BFR studies used absolute pressures (250 mm Hg) (4–6), whereas others have set relative pressures based solely on the brachial systolic blood pressure of each individual (7–9). In an effort to minimize arterial occlusion and standardize BFR occlusion pressures (same stimulus) across all individuals, research has moved toward determining the total arterial occlusion pressure (AOP) (minimum pressure applied by the cuff to completely occlude arterial flow) of each, and then using a set relative percentage of AOP (%AOP) during BFR exercise (3,10).
Utilizing the lowest possible pressure to achieve a training response is considered the safest BFR training application (11–13), and it is also advantageous as it is perceptually less stressful to the individual performing the training, which in turn can improve exercise/therapeutic treatment adherence (13,14). Nevertheless, it is not clear if applying lower cuff pressures (e.g., 40% AOP) elicits a reduction in blood flow similar to higher cuff pressures (e.g., 70%–80% AOP). Data obtained when applying cuff occlusion to the arm indicate that the relationship between %AOP and blood flow is not linear and that, to a point (~40% AOP), lower pressures are roughly as effective at restricting brachial arterial inflow as higher pressures (~80% AOP) (15). In fact, Mouser et al. (15,16) reported that decreasing cuff pressure from 80% AOP to more comfortable, lower pressures had little impact of blood flow until reaching a threshold around 20% to 40% AOP, at which point even small decreases in %AOP result in large increases in brachial artery blood flow. Interestingly, a similar study with cuff pressure applied to the legs concluded a linear relationship between % AOP and flow, despite providing plots, which to the naked eye, appear nonlinear (17). Thus, the relationship between %AOP and blood flow in the legs is not clear.
If the relationship between cuff pressure and blood flow in the leg is linear, as has been suggested (17), the increase in blood pressure associated with exercise may have a large impact on the magnitude of BFR or ischemia during exercise. For example, Barnett et al. (18) measured AOP before and immediately after exercise and found that the pressure required to elicit AOP increased with exercise, such that a pressure corresponding to 40% of the AOP measured before exercise would correspond to only 32% of the AOP measured immediately after exercise. If cuff pressure does exhibit a linear relationship with blood flow in the leg (17), such a decrease in %AOP could present a potential issue where %AOP may decrease below the prescribed occlusion training range during exercise (12), even if cuff pressure remains the same, which could limit the desired outcomes of the BFR stimulus.
Therefore, the purpose of this study was to elucidate the relationship between BFR cuff pressure on the leg and leg blood flow at rest (i.e., is the relationship between cuff pressure and flow linear?), and determine if the application of an % AOP assessed at rest (rAOP) elicits a reduction in the blood flow response during exercise comparable to that elicited by the application of a % AOP determined during the exercise (eAOP), when a greater pressure is likely needed to occlude the artery (13,18).
The study used a randomized crossover design, where each subject served as his or her own control in each of the experiments.
Twenty-three subjects (11 male, 12 female; 175.2 ± 2.0 cm, 70.33 ± 2.4 kg, and 22.78 ± 0.50 yr [mean ± SE]) were recruited from a university setting. All subjects were classified as being recreationally active (defined in this study as exercising at least three times per week for 30 min or more per exercise session). Participants were excluded if they had more than one of the following risk factors for thromboembolism, which included the following: obesity (BMI ≥ 30 kg⋅m−2); diagnosed Crohn’s disease, past fracture of the hip, pelvis or femur; major surgery within the last 6 months; varicose veins; a family or personal history of deep vein thrombosis or pulmonary embolism. All subjects completed both study 1 and study 2.
After screening, all subjects provided informed, written consent for this study, which was approved by the Brigham Young University, institutional review board in accordance with the Declaration of Helsinki. Subjects then returned to the laboratory on three occasions in a fasted state (>4 h), having abstained from exercise and alcohol for at least 24 h and having abstained from caffeine for at least 8 h before testing. Figure 1 illustrates the experimental procedures of each of the three visits.
Each day subjects reported to the laboratory, and were seated in a chair with the legs extended and supported to 180° knee extension. Subjects were then equipped with an uninflated 10 cm Hokanson cuff (Hokanson E20; Hokanson, Inc., Belleview, WA) around the upper thigh near the inguinal crease of the selected leg. A finger photoplethysmography unit (CNAP; CNSystems, Graz, Austria) was placed on the index and middle fingers to measure beat-by-beat changes in blood pressure and heart rate. As described in greater detail below, a Doppler ultrasound probe was held on the superficial femoral artery (SFA) to measure blood flow throughout the experiment. To minimize potential fatigue or soreness from one visit to the next, the experimental leg was randomly selected on the first visit and subsequently alternated for the remaining visits, such that the same leg was not studied two visits in a row. Therefore, the leg studied during visit 1, was again studied on visit 3. To account for any day-to-day variation, the AOP used for each day was determined at the start of each visit.
Study 1 (i.e., Visit 1): Determining the Relationship between Cuff Pressure and Resting Blood Flow
Measurement of rAOP
After the setup protocol and acclimation period, resting blood flow through the SFA was measured for 60 s with Doppler ultrasound as described below. Subsequently, the occlusion cuff was inflated to 50 mm Hg for 30 s and then deflated for 10 s. Each additional inflation was increased by 30 mm Hg (30 s on, 10 s off) until blood flow had been occluded. Occlusion was determined by the disappearance of Doppler velocity waveforms and absence of color flow flashes. Once occluded, the pressure was decreased in increments of 10 mm Hg (30 s on, 10 s off) until evidence of blood flow (i.e., Doppler velocity waveforms and color flow flashes) reappeared. Pressure was then increased 1 mm Hg until blood flow was no longer detected. The lowest pressure at which arterial blood flow was occluded at rest was defined as the rAOP. Once rAOP was determined, the cuff was deflated and subjects rested quietly for 5 min.
Measurement of flow at multiple percentages of rAOP
Cuff pressures were calculated (10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90%) based upon the individual’s rAOP and applied in a randomized fashion for each subject to account for possible time order effects with the application of the various cuff pressures. Specifically, the cuff was the inflated to the randomized relative pressure and a Doppler ultrasound measurement of SFA blood flow was recorded for 60 s. The cuff was then deflated and subjects rested for a period of 5 min followed by another relative pressure measurement until all %rAOP’s and Doppler ultrasound measurements were recorded. Mean arterial pressure was measured with finger photoplethysmography throughout.
After the relationship between cuff pressure and blood flow had been studied at rest, each subject’s 1RM was assessed for ankle plantar flexion exercise, in preparation for the second and third visits of the study. Plantar flexion 1RM was assessed on a Hammer Strength selectorized leg press (Life Fitness, Inc., Schiller Park, IL). The assessment of the plantar flexion 1RM was completed using the protocol prescribed by the National Strength and Conditioning Association (19), which entailed a warm-up of approximately five to six repetitions of a moderate weight, followed by a 2- to 4-min rest and increasingly heavier lifts estimated to yield two to three repetitions. The weight was then increased an additional 10% to 20% and subjects were asked to complete one repetition. If subjects successfully moved the weight through a full range of motion, the weight was increased by an additional 10% until task failure. The greatest weight lifted through a complete range of motion was defined as 1RM. Note that 2 to 4 min of rest separated each attempt.
Study 2 (i.e., Visits 2 and 3): Comparing Blood Flow during Plantar Flexion Exercise with Cuff Pressure Set to Either 40% rAOP or 40% eAOP
All subjects completed a plantar flexion BFR exercise bout under two conditions in random order over the next two visits. Other than the leg performing the exercise, the main difference between visits 2 and 3 was the way that AOP was determined during each visit. For one visit (e.g., visit 2), AOP was determined at rest (rAOP) using methodology identical to visit 1. The rAOP from visit 1 was not used for rAOP to account for potential differences in AOP from day to day or between legs. On another visit (e.g., visit 3), AOP during exercise (eAOP) was determined while the subjects performed low-intensity (20% 1RM, 30 contractions per minute), steady-state (>3 min) plantar flexion exercise (described below). When determining eAOP, subjects first performed this light exercise until Doppler velocities appeared to be plateaued (>3 min), at which point it was assumed that blood flow had reached steady state (20,21). After reaching an apparent steady state, the cuff was first inflated to the rAOP determined for visit 1 and adjusted as needed to establish eAOP. Blood flow through the SFA was measured with Doppler ultrasound during minutes 2 to 3 of unrestricted plantar flexion, as well as the entire sequence of cuff inflation and deflation. As mentioned above, the rAOP exercise condition and eAOP exercise condition were always performed on different legs and on different days to minimize the potential for soreness or fatigue from one visit to affect the next. Importantly, AOP was determined during each visit for the leg of interest.
After 20 min of rest after the determination of rAOP, a Velcro™ strap attached to a weighted cable pulley (NK664-75 DeLuxe wall pulley; NK Products, Lake Elsinore, CA) was placed around the forefoot with the weight set to 20% of 1RM. The cuff was then inflated to 40% rAOP. Subjects then completed a four-set series of 30–15–15–15 repetitions of plantar flexion exercise at a metronome-aided tempo of 30 contractions per minute, with a 60-s rest period between each set. Subjects were again instructed to perform controlled concentric and eccentric actions during the exercise. Blood flow through the SFA and blood pressure were measured throughout the entire protocol (see below).
On a separate visit, after 20 min of rest after the determination of eAOP, subjects performed the same exercise protocol as utilized in the rAOP condition, but this time the cuff was inflated to 40% of eAOP. Blood flow through the SFA and blood pressure were measured throughout the entire protocol as described below.
Measurement of SFA flow and central hemodynamics
Blood flow was measured in the SFA (~60% of the distance from the anterior superior iliac spine to the top edge of the patella) just distal to the inferior border of the cuff using a 9-MHz ultrasound sound probe (Logiq e, 9 L probe; General Electric Company, Fairfield, CT). Ultrasound gel (Aquasonic 100; Parker Laboratories, Inc., Fairfield, NJ) was used as a medium between the sound head and the subject’s skin. The insonation angle of the probe was set and maintained at 60° (22). Doppler velocity waveforms and color flow mode was inspected for the presence of arterial blood flow through the SFA. After being seated and instrumented for 15 min, resting blood flow was recorded for 60 s. The Doppler ultrasound recordings were used to determine average blood velocity (i.e., TAmean), as well as antegrade and retrograde velocity in 4-s averages. Vessel diameter was measured during end diastole from the superficial to deep wall of the SFA, perpendicular to the direction of blood flow with the calibrated software on the ultrasound system. Femoral artery blood flow was subsequently calculated with the following equation:
Blood pressure and heart rate were measured continuously with a finger photo plethysmography system (CNAP; CNSystems, Graz, Austria) placed on the first and second fingers at heart level. MAP was calculated as the pressure–time integral of the continuous finger BP measurement (22).
A mixed-model ANOVA with blocking on subjects was used to determine significance in our studies. In the event of a significant omnibus (P < 0.01), a Tukey post hoc test was performed. A lack-of-fit test was also performed to determine if the relationship between cuff pressure and flow was linearly related. Statistical significance was set at P ≤ 0.01. All data were analyzed using JMP Pro version 14.0 (JMP, Cary, NC). Data are represented as mean ± error of the mean unless otherwise stated.
Study 1: determining the relationship between cuff pressure and resting blood flow
As illustrated in Figure 2, a significant lack-of-fit test (P = 0.0001) determined that a straight line did not fit the model for average blood flow, indicating that the relationship between cuff pressure (% rAOP) and blood flow in the lower extremity is nonlinear in a seated position. Average blood flow at 10% rAOP is significantly different than 50% to 100% rAOP (P < 0.0002) and 20% is different from 80% to 100% rAOP (P value range = 0.009 to 0.0001); however, between 30% and 80% rAOP blood flow values were not significantly different (30% vs 80% P = 0.08; 40,50,60,70 vs 80%%: P = 1.00) from one another. Thus, although 30% versus 80% is trending toward being significantly different (P = 0.08), 40% to 70% versus 80% (P = 1.00) are clearly not different. The resting condition (0%) and 90% and 100% rAOP were significantly different from all other conditions (P ≤ 0.0002).
As described in Table 1, no effect of cuff pressure on MAP was detected (P = 0.80). Consequently, when considering flow in terms of vascular conductance (i.e., Flow/MAP), a nonlinear relationship between cuff pressure and vascular conductance was observed, very similar to that pictured in Figure 2. Additionally, a significant lack-of-fit test (P = 0.0001) determined that a straight line did not fit the model for average vascular conductance, indicating that the relationship between cuff pressure (% AOP) and conductance in the lower extremity is nonlinear in a seated position. As listed in Table 1, significant differences were found in conductance (P < 0.01) with decreases in blood flow occurring in a nearly identical manner as depicted in Figure 2. A detailed summary of central and peripheral hemodynamics observed during study 1 can be found in Table 1.
Study 2: comparing blood flow during plantar flexion exercise with cuff pressure set to either 40% rAOP or 40% eAOP
As illustrated in Figure 3, eAOP was significantly greater than rAOP (228.87 ± 1.5 mm Hg vs 201.49 ± 1.5 mm Hg, P < 0.01, respectively). Consequently, there was also a significant difference (P < 0.01) in cuff pressure applied during the 40% rAOP (80.5 ± 0.6 mm Hg) and 40% eAOP (91.4 ± 0.6 mm Hg) exercise conditions. Interestingly, a significant difference in occlusion pressures between legs existed (P < 0.01) with the right leg averaging 235.7 ± 1.6 mm Hg compared with 194.6 ± 1.6 mm Hg on the left leg. Note that 1RM did not differ between legs (right leg: 180 ± 10 vs left leg 180 ± 9, P = 0.42).
Figure 4 illustrates the blood flow responses to the plantar flexion exercise protocol with cuff pressure set to either 40% rAOP or 40% eAOP. Despite the difference in the cuff pressure applied to the leg between conditions, there was no significant difference in the blood flow response to plantar flexion exercise in the rAOP or eAOP conditions (P = 0.49). Regardless of condition, a significant main effect of exercise/rest period on blood flow was observed (P = 0.001). Indeed, blood flow significantly increased above resting values with each exercise bout and remained significantly elevated during recovery periods 1, 2, and 4 (i.e., Rec1, Rec2, and Rec4). Nevertheless, post hoc analyses indicated that flow that flow at every time point (4 s average) illustrated in Figure 4 was significantly less than the steady-state flow achieved during uncuffed exercise (uncuffed exercise flow = 514 ± 47 mL·min−1, P < 0.01).
Although a significant main effect of exercise/rest period on vascular conductance was observed (P < 0.001), no main effect of AOP condition nor interaction between AOP condition and exercise period was observed for vascular conductance (cuff condition, P = 0.74; interaction, P = 0.87). Furthermore, no differences in the MAP and heart rate responses between cuff conditions were observed (P = 0.17–0.98). A summary of comparisons in the hemodynamics responses for each exercise or recovery period (with data pooled from both conditions) and their levels of significance can be found in Table 2.
The purpose of this set of studies was to elucidate the relationship between the cuff pressure used during BFR on the leg and leg blood flow at rest and during exercise, with the aim of determining if lower cuff pressures provide a similar ischemic stimulus to higher cuff pressures. There were two novel findings in this regard. First, the relationship between applied cuff pressure and blood flow through the SFA is nonlinear, meaning that a given increase or decrease in pressure does not always result in a commensurate change in flow. Second, despite requiring a ~25 mm Hg greater cuff pressure to achieve full occlusion during exercise, accounting for this increase in AOP during plantar flexion has no meaningful impact on exercise flow, likely due to the nonlinear relationship between cuff pressure and blood flow. The implications of these findings will be discussed below.
The relationship between cuff pressure and leg blood flow is not linear
As illustrated in Figure 2, the results of the current study indicate that the relationship between cuff-induced pressure and blood flow in the SFA is nonlinear when measured in a seated position. While increasing from 10% to 20% AOP or 80% to 90% rAOP both significantly impacted blood flow, changing cuff pressure between 30% and 80% rAOP did not significantly impact SFA blood flow (30% vs 80% rAOP, P = 0.08; 40%–70% vs 80% rAOP, P = 1.00). Thus, while blood flow may be trending toward a difference between 30% and 80% rAOP, the data convincingly illustrate (Fig. 1) that cuff pressures ranging from 40% to 80% rAOP elicit very similar blood flow responses at rest.
The nonlinear relationship between cuff pressure and BFR is consistent with data collected by Mouser et al. (15,16) when observing brachial artery blood flow in response to varying levels of cuff occlusion applied to the arm. At first glance, our current data appear to be at odds with the other data collected by Mouser et al. (17), who concluded that cuff pressure exhibited a linear relationship with blood flow in the leg (posterior tibial artery) in a supine position. Differences in body position and measurement site (SFA vs posterior tibial artery) may account for this apparent discrepancy. Nevertheless, the plot of pressure versus flow in the study by Mouser et al. (17) visibly varies from the line of agreement, putting the conclusion of linearity into question. Moreover, similar to the current study, the flow values elicited by cuff pressures ranging from 30% to 70% rAOP appear to have not significantly differed from each other (17). Thus, when applying BFR cuff pressure to the thigh, it appears that varying pressure from ~40% to ~80% rAOP will elicit comparable reductions in resting leg blood flow.
The failure of increased cuff pressure in the range of ~40% to ~80% rAOP to elicit proportional reductions in arterial inflow could be for a variety of reasons, including a compensatory increase in perfusion pressure, and a nonlinear distribution of cuff pressure on artery diameter. Of the two possibilities, the nonlinear effect of cuff pressure to the artery seems the most likely. As described by Poiseuille’s law (23), flow through an artery is primarily influenced by the radius of the artery, which is presumably reduced by cuff occlusion, and the difference in pressure from the artery to the vein. If each increase in cuff pressure elicits a proportional reduction in the artery diameter, perfusion pressure must increase to compensate for the theoretical change in diameter for blood flow to be maintained from ~40% to 80% rAOP. As depicted in Table 1, MAP did not differ between any of the various cuff pressures applied. Consequently, vascular conductance, which normalizes blood flow for potential changes in MAP, exhibited the same nonlinear relationship as flow (Table 1). Certainly, MAP is only one half of the equation for perfusion pressure (perfusion pressure = MAP − mean venous pressure), but given the likely occlusion of the venous circulation by the cuff, an increase in mean venous pressure seems more likely under these circumstances, which would cause a decrease in perfusion pressure, not an increase. Thus, it appears that the plateau in flow from 40% to 80% rAOP is more likely related to the efficacy of the cuff pressure on the artery diameter in that pressure range, not a compensatory increase in perfusion pressure. This could be potentially due to movement of the tissues from the cuffing pressure producing unequal pressure distribution onto the artery. Owing to the inability to view the artery deep to the cuff, a direct measure of artery diameter directly deep to the cuff was not possible in this study.
Accounting for the exercise-induced increase in AOP has no effect on exercise flow
Previous studies have indicated that the pressure required to fully occlude an artery during exercise (i.e., eAOP) is likely greater than the pressure required to fully occlude the same artery at rest (i.e., rAOP) (13,18), most likely due to the increase in MAP typically associated with exercise (24). In agreement with these previous studies, the current study indicated that eAOP during plantar exercise is, on average, ~25 mm Hg greater than rAOP (Fig. 3). With eAOP being ~25 mm Hg greater than rAOP, applying 40% rAOP (~81 mm Hg), as is common practice (12), would actually only equate to approximately ~35% of the pressure needed to occlude the artery during exercise. If the relationship between cuff pressure and blood flow was linear in this range of pressures, the failure to account for the exercise-induced increase in AOP could potentially result in less flow restriction during exercise than anticipated. Nevertheless, consistent with the nonlinear relationship between cuff pressure and blood flow illustrated in Figure 1, variations in cuff pressure in this range (35%–40% AOP) had no appreciable impact on blood flow during plantar flexion exercise. Thus, the relationship between cuff pressure and blood flow appears to be nonlinear even during exercise, meaning that it is not necessary to account for differences in rAOP and eAOP when applying cuff pressure during exercise.
Implications of the nonlinear relationship between cuff pressure and blood flow
Results of our study have significant clinical and practical implications for the application of cuff pressure during BFR exercise. As one might guess, higher cuff pressures are associated with greater levels of pain and rating of perceived exertion (25). Thus, in terms of the tolerability of the exercise, lower pressures are preferable. The lack of a difference in effects of lower (~40% rAOP) and higher (~80% rAOP) on blood flow in the current study suggest that the lower, more comfortable pressures may be utilized without reducing the ischemic stimulus. In support of the equivalency of moderate and higher pressures, a 12-wk lower extremity study, which utilized BFR strength training with either 40% or 80% rAOP, indicated that training with the lower cuff pressure yielded similar gains in strength and hypertrophy to training with the higher cuff pressure (26). In another recent study (27), it was reported that low-load exercise utilizing either 40% or >80% AOP on opposite arms produced similar increases in muscle size, strength, and endurance in the upper extremity. It was also noted that the higher pressure condition produced higher ratings of discomfort throughout the training program (27). The data from our study suggest that the similarity of training adaptations with 40% and 80% rAOP is likely related to the observation that the reduction in blood flow is fairly similar with these very different pressures.
Our study was performed with subjects being in a seated position, with a 10-cm cuff size and Hokanson E-20 rapid cuff inflator device. Although there are several other types of devices (Kaatsu, B-strong, Delphi) and cuff sizes that can be utilized for exercise that yield very different cuff pressures, because the cuff pressure was primarily analyzed as a percentage of AOP, the results of this study are likely applicable to other BFR devices, regardless of type or cuff size (15), when considered in terms of %AOP. As body position can impact perfusion pressure, it is possible that the current findings may be different in a different body position (e.g., supine or standing).
During the course of the study, we alternated legs between visits to minimize soreness or training effects. Interestingly, as described in the results section, we noted a significant between-leg difference (P < 0.0001) in rAOP. As cuff pressures in this study were applied as a percent of each leg’s own rAOP or eAOP, this phenomenon likely had minimal impact on the conclusions of this study. Nevertheless, that rAOP differed between legs has potential implications for the use of a single rAOP for each leg. Additional research specifically designed to study potential between-leg differences (e.g., right vs left or dominant vs nondominant) needs to be completed to determine the importance of this unexpected observation.
When performing BFR on the thigh (SFA), cuff pressure exhibits a nonlinear relationship with blood flow, such that approximately similar reductions in blood flow associated with a cuff pressure of 80% rAOP can be achieved with pressures around 40% rAOP. Furthermore, despite an exercise-induced increase in the pressure required to obtain arterial occlusion during exercise, utilizing 40% of the AOP determined at rest results in the same BFR as utilizing 40% of the higher AOP determined during exercise. Together, these data indicate that lower, potentially more-comfortable, cuff pressures can be applied during BFR to obtain a reduction in blood comparable to higher, less-comfortable pressures.
The authors thank the subjects for their generous participation. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Additionally, the results of the present study do not constitute endorsement by ACSM.
Funding: This study was funded in by an IRA Fulton College of Life Sciences Grant, and by the BYU Inspiring Learning Funds.
Disclosures: The authors have no conflicts of interest to report.
The results of the present study do not constitute endorsement by ACSM. This study was funded in by an IRA Fulton College of Life Sciences Grant, and by the BYU Inspiring Learning Funds. The authors have no conflicts of interest to report.
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