There have been an increasing number of reports in the literature regarding the effects of exercise training with deliberate restriction of venous blood flow on skeletal muscle adaptations. This form of training, known as "occlusion training" or Kaatsu, serves as a powerful stimulant for rapid increases in specific metabolic enzymes, muscle mass, and strength (1,20-22). In fact, the muscle adaptations seen with restrictive venous blood flow training protocols suggest that the improvements can be accomplished with much lower intensities of exercise, which may represent an alternative method of training for individuals intolerant to higher-intensity training protocols. Interestingly, few studies have examined the concurrent vascular responses following restrictive venous blood flow training protocols.
Findings from our laboratory have consistently reported that regional-specific resistance training results in large conduit artery adaptations (2,3,9). In addition, our data show a direct association between vascular and physical function (e.g., muscular strength) (26). The underlying trigger for such adaptations and associations is believed to be muscular contraction-induced increases in local shear forces that contribute to vascular modifications including endothelial-mediated dilators (11). Given the consistent evidence that vascular function is linked to muscular strength (26), we anticipate that the muscular benefits with occlusion training would extend to the vasculature as well.
Thus, the purpose of the present study was to examine the effects of 4 wk of handgrip exercise training combined with or without restricted venous blood flow on handgrip strength and brachial artery dimensions and vasodilation. We hypothesized that handgrip exercise training with venous restriction would result in superior strength gains and vasoreactivity compared with the nonrestricted arm.
Twelve participants (mean ± SD: age = 22 ± 1 yr, men = 5, women = 7) were selected from the kinesiology student body at the Louisiana State University. Before initiation of the study, subjects completed a medical history or health habits questionnaire. In addition, all subjects were familiarized with the equipment and experimental procedures. Exclusion criteria were any diagnoses or evidence of cardiovascular, metabolic, orthopedic, and/or neurological disease; active infection; risk for adverse responses to exercise; and/or taking any medication that may affect cardiovascular function. Each participant signed an informed consent approved by the institutional review board of the Louisiana State University and Agricultural and Mechanical College.
Assessment of handgrip strength.
Handgrip strength was measured using a hydraulic hand dynamometer (Baseline®, Irvington, NY). The subject was asked to perform a maximum voluntary contraction (MVC), standing with the dynamometer at one side and gripping the dynamometer as hard as they could for 3 s. This was repeated three times for each hand. The average of the three trials for each hand was considered to be the maximum voluntary handgrip strength. Forearm circumference was examined using a weighted measuring tape positioned 10 cm distal to the midpoint between the lateral epicondyle and the olecranon process. All pretraining assessments were performed within the week before commencement of training. Handgrip strength trials were performed 5 min after ultrasound assessments. These tests were performed before and after the final week of training. The right arm was assessed first each time, and subjects were allowed 1 min of rest between handgrip trials.
Assessment of vascular function and blood velocity profiles.
All brachial artery imaging was conducted by the same ultrasonographer in accordance with the "International Brachial Artery Reactivity Task Force" guidelines (5). Testing was performed between the hours of 7:00-11:00 a.m. Participants were required to refrain from caffeine before imaging. Subjects were also instructed to fast and refrain from strenuous activity for 12 h and from alcohol for 48 h. In addition, subjects completed a 24-h history questionnaire recalling past meals, drinks, activities, sleep, and medications taken. Baseline ultrasound images were obtained after 20 min of supine rest in a dark, climate-controlled, quiet room (22°C-24°C), with the participants arm immobilized and slightly supinated and elevated. An additional 10 min of rest was given before imaging the opposite arm. The right arm was imaged first in each case.
All brachial artery imaging and velocity profiles were obtained using a Hewlett-Packard Sonos 2000 (Bloomfield, CT) Doppler ultrasound, with a 7.5-MHz linear array transducer. Images were obtained in the longitudinal view, approximately 4 cm proximal to the olecranon process, in the anterior or medial plane. Image depth was set at 4 cm, and gain settings were adjusted to provide an optimal view of the anterior and posterior intimal interfaces of the artery and kept constant throughout. Doppler velocity profiles were collected simultaneously using a pulsed Doppler signal at a corrected insonation angle of 60° to the vessel, with the velocity cursor positioned to sample the volume, mid artery.
Forearm occlusion consisted of inflation of a pneumatic cuff (E-20 rapid cuff inflator, AG-101 air source; D.E. Hokanson, Bellevue, WA) positioned approximately 1 cm distal to the olecranon process, inflated to 200 mm Hg for 5 min. Images for vessel diameter and velocity profiles were obtained for 30 s at rest and continuously from the final 30 s of occlusion until 2 min after the release of the blood pressure cuff. In addition, heart rate and blood pressure were monitored throughout the imaging process. Heart rate and blood pressure were recorded using the ECG from the ultrasound and an automated blood pressure device (Datascope-Accutorr 4®; Mindray DS USA, Mahwah, NJ) before, during occlusion, and after release of the pneumatic cuff. The ultrasound images were recorded digitally and saved on disc for subsequent offline analysis.
An examination of the blood velocity profile during handgrip exercise was also performed. In one arm, a cuff was placed on the forearm, approximately 4 cm distal to the antecubital fossa. It should be noted that only six individuals participated in the experiment to examine blood velocity patterns during exercise, with restricted venous blood flow, after completion of the study. Three women and three men were selected for blood velocity during exercise experiment. The purpose of this additional experiment was to assess the impact of partial forearm vascular occlusion on brachial artery blood velocity patterns. It should be noted that the magnitude of blood flow was not pertinent to this particular investigation, only the pattern of the velocity profiles (e.g., antegrade and retrograde profiles). In addition, when performing the Doppler ultrasound imaging of the brachial artery during handgrip exercise, the blood pressure cuff was placed distal to the position that was used during the actual training intervention. This distal position was chosen to facilitate the placement of the ultrasound probe. The training session followed the same protocol as the study (see Exercise training section). A total of five, 10-s ultrasound images were recorded in each arm (at rest and during 5, 10, 15, and 20 min of exercise).
Offline analyses of diameters were analyzed similar to previously published reports (9,26), using a semiautomated edge-detecting software, Brachial Analyzer (Medical Imaging Applications, LLC, Coralville, IA). The reproducibility of this technique in our laboratory has yielded average mean differences in brachial artery diameter change for days and testers of 1.91% and 1.4%, respectively, with intraclass correlation coefficients of 0.92 and 0.94, respectively (25). Arterial diameters were calculated as the mean distance between the anterior and the posterior wall at the blood vessel interface, with the image in diastole, defined as the peak of the R wave on the electrocardiograph. Resting diameter was defined by the average of 30 s of data obtained after 20 min of resting conditions. Peak dilation was defined as the largest diameter after release of the occluding cuff. Finally, brachial artery flow-mediated dilation (BAFMD) was defined as the percent change in vessel diameter from rest to peak diameter after forearm occlusion.
Blood velocity profiles were analyzed similar to previously published reports (6,9). Each profile was traced using Image Pro Plus 4.0 software (Media Cybernetics, Bethesda, MD). The antegrade component was defined as the area of tracing above 0 cm·s−1 from the Doppler ultrasound scale, and the retrograde component was defined as the area below. The velocity profiles were then divided by the ejection time (s) from that cardiac cycle to subsequently determine the mean velocity (cm·s−1). The mean velocity (Vmean) during baseline was calculated as the difference between the antegrade and the retrograde velocity components. To establish an estimate of oscillatory flow patterns, a ratio was taken between the antegrade and the retrograde flow velocities (antegrade/retrograde ratio) (6). Shear rate (4 × Vmean (cm·s−1) / diameter (cm)) was measured at 10-s intervals during reactive hyperemia up to the point of maximum vessel diameter and plotted against time (s). A trapezoidal model was then used to calculate area under the curve (AUC) above baseline (9,19). During a handgrip training session, three blood velocity profiles were traced within 2 min of each time point (at rest and during 5, 10, 15, and 20 min of exercise) before a muscular contraction and averaged to determine flow velocity patterns during each time point of exercise.
Exercise training involved gripping a hydraulic hand dynamometer (Baseline®) and contracting the forearm at a rate of 15 times per minute (one contraction every 4 s) at the pace of an electronic metronome and a resistance of 60% of MVC. The intensity was marked on the gauge of the handgrip dynamometer using a dry-erase marker. The subjects were asked to train for 20 min, 3 d·wk−1 for 4 wk, at the Louisiana State University, under the supervision of a laboratory technician. Throughout the study, the participants were positioned facing two small mirrors to allow for a visual reference of the handgrip dynamometer. Subjects trained both hands, at the same time. However, for one of the limbs, the pneumatic blood pressure cuff was placed on the upper arm, 4 cm proximal to the antecubital fossa. The decision which arm would receive the occlusion during training was randomized to avoid a dominant or a nondominant hand bias.
During the training, this blood pressure cuff was partially inflated (80 mm Hg) to ensure venous occlusion. Although some arterial inflow may have been restricted, the purpose was to induce venous pooling within the forearm vasculature. Previous work using restricted venous blood flow in the legs has indicated that the application of 100 mm Hg was significant enough to restrict venous blood flow and to cause venous pooling in the thighs distal to the cuff (14). The current study examined venous restriction in the forearm, and the application of 100 mm Hg caused discomfort and exercise intolerance during handgrip training. An occlusion pressure of 80 mm Hg was tolerable and sufficient, given that the average resting diastolic blood pressure in the experimental (EXP) arm for the participants was approximately 71 mm Hg. Subjects were allowed to take 1-min rest periods after the completion of 5 min of training while the cuff remained inflated but were encouraged to progress through each session.
Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows (Version 17.0; SPSS Inc., Chicago, IL). Data are presented as mean ± SD. To determine the effects of the 4 wk of handgrip exercise training on handgrip strength and BAFMD, a 2 (EXP arm vs control (CON) arm) × 2 (pretraining vs posttraining) repeated-measures ANCOVA was performed, using the baseline (pretraining) measures as the covariate. To determine gender differences for the magnitude of change in BAFMD and handgrip strength after exercise training, an ANCOVA was performed (men vs women), using the baseline (pretraining) measures, MVC and BAFMD, as the covariate. To examine the change in blood velocity patterns (antegrade/retrograde ratio and shear rates) during exercise training, a subsequent 2 (EXP arm vs CON arm) × 5 (velocity at rest and 5, 10, 15, and 20 min of exercise) repeated-measures ANOVA was performed. Differences between means were evaluated using a post hoc LSD test. An alpha level of P ≥ 0.05 was required for statistical significance.
Twelve participants completed all facets of this study. All individuals were free of symptoms indicative of chronic illness. No one was taking any vascular medication that may influence the results. The baseline characteristics of these individuals are presented in Table 1. Resting systolic and diastolic blood pressure for the participants (pretraining and posttraining) averaged 116 ± 9/71 ± 8 and 113 ± 8/71 ± 7 mm Hg, respectively. The average height for men and women in the present study was 185.93 ± 4.89 and 168.37 ± 6.8 cm, respectively. The average weight for the men and women was 94.09 ± 13.02 and 68.7 ± 10.95 kg, respectively.
Handgrip strength and forearm circumference.
All subjects completed a total of 12 training sessions. There were no significant strength or circumference differences between arms before training. The results of the ANCOVA for handgrip strength (covariate = baseline MVC) revealed an increase in strength for the CON arm (8.32%, P = 0.05) and the EXP arm (16.17%, P = 0.05). These results are illustrated in Figure 1 as the mean change in handgrip strength (kg) between study arms after 4 wk of handgrip exercise. It should be noted that there was no significant gender difference between men and women for the magnitude of change in handgrip strength (P = 0.36). After training, there was also a significant increase in forearm circumference for the CON (1.62%: pretraining = 24.80 vs posttraining = 25.20 cm, P = 0.05) and EXP arms (2.42%: pretraining = 24.80 vs posttraining = 25.40 cm, P = 0.05).
Assessment of vascular function and blood velocity profiles.
Values for vascular diameters are presented in Table 2. No significant differences in baseline brachial diameter, BAFMD, or velocity profiles were noted between arms before training. The average baseline brachial diameters were EXP arm = 4.21 ± 0.34 mm and CON arm = 4.29 ± 0.25 mm for men and EXP arm = 3.45 ± 0.42 mm and CON arm = 3.54 ± 0.6 mm for women. Figure 2 presents the results from the ANCOVA for BAFMD, pretraining, and posttraining. BAFMD increased in the CON arm (24.19%, P = 0.0001; absolute change: pretraining = 0.22 ± 0.01 mm vs posttraining = 0.29 ± 0.11 mm) and decreased in the EXP arm (30.36%, P = 0.0001; absolute change: pretraining = 0.27 ± 0.07 mm vs posttraining = 0.19 ± 0.06 mm). There were no significant gender differences for the magnitude in change in BAFMD (P = 0.11). Figure 3 presents the actual BAFMD values, between study arms, for the individuals after 4 wk of handgrip exercise. Mean values for blood velocity profiles and shear AUC, pretraining and posttraining, are presented in Table 3.
An examination of the blood velocity pattern during exercise revealed that upon inflation of the cuff, before exercise, the retrograde flow velocity component increased (preinflation = 1.27 cm·s−1 vs postinflation = 13.49 cm·s−1, P = 0.03) and the antegrade velocity decreased (preinflation = 17.96 cm·s−1 vs postinflation = 14.68 cm·s−1, P = 0.05). Consequently, the antegrade/retrograde ratio decreased significantly (preinflation = 14.14 cm·s−1 vs postinflation = 1.09 cm·s−1, P = 0.05) after cuff inflation in the EXP arm. Furthermore, the retrograde flow velocity component remained for the occluded arm, with no such evidence in the nonoccluded arm. Figure 4 illustrates the mean antegrade and retrograde shear rate (s−1) values during the training session.
The present study examined the effects of 4 wk of handgrip exercise training, coupled with and without restricted venous blood flow, on handgrip strength and brachial artery vasodilation. The data indicate that forearm exercise training combined with restricted venous blood flow results in a significantly different change in muscular strength (superior strength gains) and vascular function (reduced vasodilation) compared with the nonrestricted arm.
Handgrip strength and forearm circumference.
The present study observed significant improvements in handgrip strength and forearm circumference after regional-specific handgrip training. These results compare to others who have observed the effects of regional-specific exercise on handgrip strength changes (2,3). Alomari and Welsch (3) reported a 14.5% improvement in grip strength after 4 wk (five sessions per week) of handgrip exercise training. Interestingly, the present study reports a significantly greater improvement in grip strength in the EXP arm compared with the CON arm.
Previous studies have shown that combining resistance training with restricted venous blood flow results in significant improvements in muscle size and strength (20-22). Consistent with this statement, the present study confirms a 50% greater improvement in handgrip strength in the EXP arm compared with the CON arm. Mechanisms that could have contributed to this increase in strength are not entirely understood but have been proposed to be the consequence of an up-regulation in specific growth factors (e.g., IGF-I) (1) and specific metabolic enzymes (e.g., creatine phosphokinase) (1), the result of hormonal changes (e.g., increase in growth hormone) (1), and/or a preferential recruitment of larger, fast motor units (17,20).
Vascular function and blood velocity profiles.
Brachial artery resting diameter, before training, was similar between arms and to previous reports from our laboratory (2,8) and significantly associated with BAFMD before training (r = 0.57, P = 0.04). Moreover, the average vasodilatory response after 5 min of occlusion, before training, were also similar between arms and in agreement with Dobrosielski et al. (8), who reported a BAFMD value of 7.7% ± 3.5% in healthy adults (age = 28 ± 8 yr).
The present data indicate that after 4 wk of handgrip exercise training, BAFMD improved 24.19% in the CON arm. In fact, 10 of 12 arms showed improvements after training, indicating the consistency of the adaptive response. However, the observed improvement is less than that previously reported by Allen et al. (2). In that study, BAFMD improved 62% after 4 wk of handgrip exercise training using a protocol of 20 min·d−1, 5 d·wk−1. The discrepancy between studies could in part be the result of a significantly lower volume of training in the present study (∼50% less).
Typically, improvements in BAFMD with exercise training are believed to be secondary to the changes in shear stress induced by the muscular contractions during the acute bouts of exercise (11). The muscular contraction-induced changes in shear stress are thought to alter the endothelial machinery involved in vasodilatory pathways, including increased nitric oxide production, eNOS, PGI2, antioxidant defenses, and reduction in reactive oxygen species, adhesion molecules, and vasoconstriction factors (e.g., endothelin 1) (11,13,15). We also acknowledge that the improvement in BAFMD, in the present study, may also be the result of endothelial independent changes in resistance vessel function and microcirculation (11) because the relevant shear stimulus was higher at week 4 in both the CON and the EXP arms compared with the pretraining measures. The fact that in the EXP arm BAFMD declined after training despite higher shear AUC is intriguing and suggests a significant alteration in the vasodilatory response to a larger trigger.
Uniquely, the present study observed a significant reduction in BAFMD in the EXP arm. The reduction was apparent in 9 of 12 arms and appeared to be greatest in those who had the highest pretraining BAFMD, suggesting those individuals "suffered" to a greater extent than those who had lower vascular function before training. The fact that the change in vascular function is completely in the opposite direction of the CON arm is quite intriguing. Interestingly, a recent study examined oxidative stress in response to partial vascular occlusion of the upper arm in young men (10). Goldfarb et al. (10) found an elevation in oxidative stress, as defined by a glutathione ratio and plasma protein carbonyls, in response to moderate-intensity resistance training as well as with prolonged vascular occlusion (e.g., 20 mm Hg less than resting diastolic pressure). The present study used a similar occlusion pressure and exercise training intensity, which could have resulted in an elevation in oxidative stress within the EXP arm. This is important considering the inherent effects of oxidative stress on endothelial function (12,13).
An additional explanation for the decline in BAFMD observed in the EXP arm stems from the hypothesis that regular exposure to exercise induced increases in endothelial "shear stress" is the primary signal for a positive expression of endothelial function (11,13,15,16,27). A reduction or an alteration of the shear stimulus during exercise may compromise the vascular adaptive response. In fact, in the present study, upon inflation of the cuff and before exercise in the EXP arm, the retrograde velocity component increased, and the antegrade velocity component decreased. Consequently, the antegrade/retrograde ratio decreased significantly after cuff inflation in the EXP arm. The fact that handgrip exercise with restricted venous blood flow has such a large retrograde component, in comparison with antegrade, suggests that there may be a significant change in oscillatory flow patterns and shear stress (6,16,23,24). Such a shear stress is thought to promote a proatherogenic phenotype and oxidative stress within the endothelium, resulting in a decline in vascular function (7,16).
The examination of flow velocity patterns during exercise should be interpreted within the constraints of potential limitations. Our study used a noninvasive measure of blood velocity and flow. It is difficult to establish an estimate of oscillatory flow patterns within a vessel with two-dimensional imaging. However, it is interesting to see that these patterns change when exposed to an increase in resistance (e.g., restricted venous blood flow). The findings that the flow patterns are changed during restrictive flow conditions are in agreement with Tinken et al. (24), who reported that during handgrip exercise, cuffed arm retrograde flow was higher than that in the noncuffed. In fact, BAFMD was not significantly changed in the cuffed arm in response to acute bouts of heating, handgrip, and cycling (24). In another study, Thijssen et al. (23) reported that acute alterations in flow velocity patterns, at rest, resulted in a reduction in subsequent measures of BAFMD. In that study, it was noted that with increasing occlusion pressures (50-75 mm Hg), there was a dose-response reduction in reactivity of the brachial artery. The apparent reduction in reactivity seen with Thijssen et al. (23) may also have been, in part, the consequence of a change in pressure exerted upon the arterial wall (18). Interestingly, Padilla et al. (18) observed a decline in vascular reactivity in the brachial artery when acutely exposed to an increase in hydrostatic pressure.
Clinical relevance and future recommendations.
Finally, from a clinical perspective, it is critical to understand that alterations in regional blood flow patterns due to vascular disease (peripheral vascular disease) may affect the exercise adaptation. Perhaps, a change in regional flow patterns in patients with peripheral arterial disease may explain why they experience an acute inflammatory response with a subsequent reduction in BAFMD after an acute bout of exercise (4). Given this evidence, future studies should investigate the effects of moderate-intensity exercise training with partial vascular occlusion on markers of oxidative stress (e.g., peroxynitrite, superoxide, and reactive oxygen species) and endothelial function (e.g., flow-mediated dilation). In addition, given the milieu of hemodynamic forces exerted upon the arterial wall, future investigations should continue to target the underlying mechanisms involved in vascular responses and adaptation.
These data indicate that forearm exercise training combined with restricted venous blood flow results in a significant increase in muscular strength, coupled with a significant decrease in vascular function (reduced vasodilation). The contrasting change in vascular function after exercise training with venous blood flow restriction in the forearm may in part be the consequence of significant alterations in blood flow patterns during handgrip exercise.
The authors thank Travis Godawa, Anna Lyons, and Vanessa Dueñas for their dedication, commitment, and technical support.
This research was supported by a grant from the National Institute on Aging (1 P01 AG022064) (S.M. Jazwinski).
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
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Keywords:©2010The American College of Sports Medicine
BLOOD FLOW RESTRICTION; REGIONAL EXERCISE; VASCULAR FUNCTION; MUSCULAR STRENGTH