The effects of whole body vibration training combined with blood flow restriction on von Willebrand factor response

Abstract

BACKGROUND:

Blood flow restriction (BFR) exercise benefits muscle performance. However, there is limited research on vascular dysfunction, particularly using involuntary muscle contraction modality plus BFR.

OBJECTIVE:

To investigate the acute and accumulative effects of whole body vibration (WBV) with BFR on vascular dysfunction, as evaluated by von Willebrand factor (vWF) levels.

METHODS:

Physically inactive men were randomly assigned to the WBV $+$ BFR group ( $n=$ 8) and the WBV group ( $n=$ 8). Participants in the WBV group were subjected to 10 sets of internment WBV exercise 20 min/day, 3 days/week for 8 weeks. Participants in the WBV $+$ BFR group received the same WBV treatment, but the proximal portion of the thighs was compressed by inflatable cuffs.

RESULTS:

The increase in vWF levels in the acute WBV $+$ BFR group was significantly higher ( $P<$ 0.05) by 17.2% than that in the WBV group. However, vWF levels exhibited equal decrements in the two groups after training ( $P>$ 0.05).

CONCLUSIONS

: WBV $+$ BFR may acutely cause vascular dysfunction potential to a greater extent than WBV alone. However, regular WBV and WBV $+$ BFR training may produce an equally beneficial effect on vascular function in a previously untrained population.

1. Introduction

Blood flow restriction (BFR) resistance training has attracted a great deal of attention in the past few decades. This training method typically compresses the proximal portion of the limbs during relatively low-load resistance exercise [20%–30% of a one-repetition maximum (1-RM)] to reduce venous return while partially restricting arterial inflow to the muscle [1, 2]. BFR resistance exercise has largely been reported to have both an additive effect on muscle performance [1] and augmenting several acute physiological responses [3]. Due to the mechanical compression of the occluded vessels, structural damage occurs [4], and the ischaemic environment derived from BFR may lead to thrombosis [5], which raises the concern that BFR resistance training may impact vasculature function. Nevertheless, research on the issue of vascular dysfunction is limited.

An alternative method to assess vascular endothelial function commonly involves measuring the levels of the biomarker von Willebrand factor (vWF) [6]. The vWF is a complex glycoprotein involved in haemostasis [6]. It mediates proper adhesion of platelets to the endothelium, which plays a major role in blood coagulation [6]. When vascular endothelial cell damage occurs, vWF is released into the bloodstream and considered to be an indicator of endothelial function [6, 7]. Higher vWF levels have been detected in clinical populations than in healthy individuals [8, 9]. Regarding the effects of exercise on vWF response, both acute endurance and resistance exercise have been demonstrated to elevate vWF levels in a healthy population [10, 11, 12, 13]. Exercise-induced increases in shear stress from increased blood flow, heart rate (HR) and blood pressure have been believed to increase platelet counts, thus increasing the levels of vWF [14]. In contrast, vWF levels were found to decrease after regular training [12, 15]. Regarding BFR resistance training, only one study has been conducted that showed that vWF levels were decreased after regular low-load BFR resistance training but remained unchanged in the same resistance training without BFR [3]. In that study, the vWF data of the acute response were not available. Taken together, it appears that the deteriorating phenomenon of vascular dysfunction may occur only in acute exercise, and regular training would not only compromise the dysfunction but also lead to vascular function improvement. However, in the event that exercise modality in nature has the potential to cause acute vWF elevation, whether additional BFR would magnify both acute exercise response and chronic training adaptation remain to be explored.

Considering that the additive effect of BFR resistance training is often observed under resisting a relatively low load, recently, the concept of resisting relatively low-force exercise with BFR has also been incorporated into vibration exercise – a reflexive muscle contraction modality [16, 17, 18]. Vibration, particularly whole body vibration (WBV), has become a popular strategy as an alternative training modality that has favourable effects on muscle fitness [19]. It has also been reported that these oscillating characteristics evoked by WBV can acutely increase the muscle blood flow, consequently leading to optimisation of vascular function [20]. WBV benefits populations such as load-contraindicated individuals who find it difficult to engage in active resistance training or to maintain even regular physical activity. Studies have demonstrated that participants exhibited a greater acute response of HR, lactate levels and rating of perceived exertion, as well as muscle activation, when exposed to WBV applied with BFR [16, 18]. These findings may reveal that exposure to WBV $+$ BFR provides a basis for greater training potential in physiological adaptation. Regarding WBV in the context of vWF, there is limited research and previous findings have indicated that vWF levels were significantly increased following vibration exposure [21]. However, data on vWF levels in response to acute and regular WBV $+$ BFR exercise are currently unclear.

Therefore, this study was conducted to investigate the acute and cumulative effects of WBV $+$ BFR exposure on vWF response and to investigate whether WBV $+$ BFR is more effective in acute and cumulative response than WBV alone. We hypothesised that WBV $+$ BFR would elicit both acute and chronic exercise responses to a greater extent than isolated WBV.

2. Material and methods

2.1 Participants

A total of 16 untrained men volunteered to participate in this study. All participants were identified to be physically inactive by screening with the International Physical Activity Questionnaire-Short Form [22]. Participants were randomly divided into a WBV $+$ BFR group ( $n=$ 8; age: 21.12 $\pm$ 0.74 years, height: 173.25 $\pm$ 1.93 cm, body mass: 69.62 $\pm$ 4.91 kg) and a WBV group ( $n=$ 8; age: 20.48 $\pm$ 0.09 years, height: 172.5 $\pm$ 1.93 cm, body mass: 66.63 $\pm$ 3.95 kg). The Institutional Review Board of Kaohsiung Medical University Chung-Ho Memorial Hospital approved all the methods and procedures used in this study, and all participants provided the written informed consent.

2.2 Experimental procedures

This study used a randomised trial design, where the participants were randomly divided into WBV $+$ BFR and a WBV groups. The study protocol comprised the measurement of baseline HR and vWF, assessment of the acute effects of WBV $+$ BFR training, conducting WBV $+$ BFR or WBV training for 8 weeks, and post-training measurement of vWF measured at baseline. The post-training measurements were performed 36–48 h after the last bout of exercise to avoid the acute effect of exercise. For analysis of vWF, blood samples were collected before, immediately after and 8 weeks after the end of the training program.

One week before the experiment, the participants were familiarised with the experimental procedures and devices. Subsequently, the participants in the WBV group performed 10 sets of internment static WBV exercise for 20 min/day, 3 days/week for8 weeks. The participants in the WBV $+$ BFR group received the same WBV treatment, but the most proximal portion of both thighs was compressed using inflatable cuffs.

The acute effect of exercise was assessed on the first training day. On the assessment day, the participants arrived at the laboratory between 07:30 and 09:00 hours and rested for 10–15 min. The lowest HR recorded during this period was considered as the resting HR. A registered nurse then collected fasting blood samples from the participants in the sitting position for baseline measurements. The participants then completed 10 sets of WBV exercise with or without BFR. At the end of each set, the participants’ HR values were recorded. Immediately after exercise, blood samples were collected again from each participant in the sitting position.

To investigate the long term effects of 8-week WBV with or without BFR training on vWF adaptation, fasting blood samples were collected again between 07:30 and 09:00 hours from the participants in the resting condition in the sitting position.

In addition to the first training session performed in the morning, each participant was trained on the same separate days each week at approximately the same time each day for the duration of the study. All measurements and training were performed in a thermoneutral room, which was maintained at 24 ${}^{\circ }$ C–26 ${}^{\circ }$ C and 40%–60% humidity, and all training sessions were conducted strictly under the direct supervision of persons technically familiar with WBV and BFR training.

2.3 WBV protocol

Each participant was trained three times per week for 8 weeks. The WBV program begins with a relatively low-training intensity but slowly progresses according to the overload principle. The progressive WBV training protocol and vibration frequency at the beginning was adapted from previous studies, which have reported a greater acute physiological response, e.g. HR, lactate and muscle activation, when external BFR was applied [16, 18]. In addition, the vibration frequency used at the beginning of the current study has previously been reported to increase muscle blood flow [20], which is a part of the initiator of shear stress. Briefly, the participants stood on a commercially available platform (BH YT18, Taipei, Taiwan) in a static squat position at 100 ${}^{\circ }$ of knee flexion, with their hands placed on the rigid lever arms, and were instructed to wear thin socks without shoes. The participants were exposed to 10 sets of WBV, each with a 1-min duration and 1-min rest between sets, except for 2 min of rest allowed after the fifth treatment. During the rest intervals, the participants were instructed to stand on the vibration platform. The amplitude of vibration was 4 mm (peak-to-peak), and the frequency was progressively increased every eight sessions for that individual in 4-Hz increments from 26 to 34 Hz of the vibration.

Table 1

Changes in heart rate and von Willebrand factor levels before and after initial WBV and WBV $+$ BFR exercise (means $\pm$ SE)

		Pre	Post	Delta (%)	Between-group difference
HR (beat/min)	WBV $+$ BFR ( $n=$ 8)	71.25 $\pm$ 4.29	116.55 $\pm$ 3.12	66.16*	17.45‡
	WBV ( $n=$ 8)	71.63 $\pm$ 3.38	105.17 $\pm$ 2.33	48.71*
vWF (%)	WBV $+$ BFR ( $n=$ 8)	90.86 $\pm$ 7.76	113.59 $\pm$ 13.37*	23.39*	17.12.‡
	WBV ( $n=$ 8)	78.10 $\pm$ 6.06	82.68 $\pm$ 5.98*	6.27*

*Significantly different from pre-test values, as determined by paired $t$ -test ( $P<$ 0.05). ‡Changes significantly greater than those in the WBV group, as determined by analysis of covariance ( $P<$ 0.05). HR $=$ heart rate. vWF $=$ von Willebrand factor. WBV $+$ BFR $=$ whole body vibration plus blood flow restriction. WBV $=$ whole body vibration.

Figure 1.

vWF levels before and after the training period (means $\pm$ SE). * Significantly different from pre-training values, as determined by paired $t$ -test ( $P<$ 0.05). vWF $=$ von Willebrand factor. WBV $+$ BFR $=$ whole body vibration plus blood flow restriction. WBV $=$ whole body vibration.

2.4 BFR device and pressure applied

The BFR device is custom-made and similar to a handheld sphygmomanometer. The device is composed of two inflatable cuffs (made of nylon; width $=$ 9 cm, length $=$ 70 cm), a hand bulb pump with a check valve, a pressure gauge and rubber tubes. The two cuffs are connected to the hand bulb pump by the rubber tubes, through which air passes during pumping. Another tube from the bulb connects the pressure gauge, in which the pressure of the cuffs is obtained. The occlusion target pressure for participants in the WBV $+$ BFR training was calculated based on mid-thigh circumference [50–55 cm, 160 mm Hg ( $n=$ 5); 55–60 cm, 180 mm Hg ( $n=$ 3)] because arterial occlusion pressure is largely influenced by thigh circumference, which needs to be adjusted for limb circumference [23]. The pressure was maintained throughout the duration of exercise (20 min), including rest periods. Cuff air pressure was released immediately upon completion of each session.

2.5 HR response

The participants’ HR was measured before and during the first training session using an HR monitor (Garmin Forerunner 935, Taipei, Taiwan). Immediately at the end of each set of exercise sessions, HR was recorded and averaged for statistical analysis. The average value for the 10 sets was calculated for statistical analysis based on a previous study [16] to represent a more accurate assessment of the entire exercise session.

2.6 Blood sample collection and analysis

Blood samples were collected from the antecubital vein and stored at 4 ${}^{\circ }$ C. Then, they were centrifuged at 1500 rpm for 30 min within 2 h of sampling. The obtained serum samples were sent to the clinical laboratory for further assays. For the quantitative determination of von Willebrand Factor Antigen (vWF:Ag), vWF levels in sodium citrate plasma samples were estimated via enzyme-linked immunoassays), that were performed according to the manufacturer’s instructions. Plasma vWF:Ag values are generally expressed in relative percent compared to pooled normal plasma.

2.7 Statistical analyses

Data are expressed as mean $\pm$ standard error (SE). Analysis of covariance (ANCOVA) was used to evaluate effects in acute exercise and regular training between the two groups, using the pre-exercise values as covariates. Pre-to-post within-group differences were also analysed using a paired $t$ -test. Statistical significance was accepted at $P<$ 0.05 for all tests.

3. Results

HR values were obtained by averaging the results of 10 sets of each treatment session. The paired $t$ -test showed that after the initial exercise, the HR response was significantly increased compared to that before the exercise in both groups ( $P<$ 0.05, Table 1). The ANCOVA results demonstrated that the increase in HR was significantly higher in the WBV $+$ BFR group than in the WBV group ( $P<$ 0.05, Table 1).

Acute changes in vWF levels before and after the initial exercise are presented in Table 1. The paired $t$ -test showed that the vWF levels were significantly increased in the WBV $+$ BFR group by 23.39% ( $P<$ 0.05) and in the WBV group by 6.27% ( $P<$ 0.05). Furthermore, the ANCOVA results revealed that the increase in vWF levels was significantly higher ( $P<$ 0.05) in the WBV $+$ BFR group than in the WBV group.

Figure 1 shows the vWF levels before and after the 8-week training regimen. As shown in the figure, the vWF levels were significantly decreased in both groups after training ( $P<$ 0.05). The decrements between the two groups were equal as determined by ANCOVA ( $P>$ 0.05).

4. Discussion

The principal finding of the present study was that acute WBV exercise with BFR can lead to augmentation of vWF response compared with isolated WBV. However, after an 8-week training programme, both WBV $+$ BFR and WBV training sessions elicited similar decrements in vWF response in the previously untrained male adults in our study.

The acute HR response in the present study was similar to that in previous findings obtained using a similar protocol, wherein external BFR manipulation to WBV resulted in an additive effect in eliciting HR response compared to that in the non-BFR-treated WBV group [16]. In addition, although we did not compare EMG amplitude between WBV and WBV $+$ BFR groups, a previous study using a similar protocol found that WBV $+$ BFR exercise yields greater EMG amplitudes in the quadriceps muscles, suggesting higher muscle force exertion. Taken together, these data suggest that exposure to WBV $+$ BFR achieves greater exercise intensity than exposure to WBV alone. Furthermore, exposure to a series of intermittent WBV treatment sessions elevated vWF levels. These findings are similar to those of Pope et al. who observed that vWF was increased in the blood after exposure to WBV exercise [21]. These findings are also consistent with previous studies using maximal [10, 11] and submaximal exercise [12] as well as resistance exercise [13] in a healthy population. In a cycling study, vWF levels were increased after one bout of session but returned to baseline the next day [24]. Similarly, Creighton et al. demonstrated that the elevation of vWF levels returned to baseline at 60 min after resistance exercise [13]. However, other studies have demonstrated that vWF levels remained unchanged after acute resistance exercise in patients with coronary heart disease [25] and decreased after maximal treadmill exercise in participants with hypertension [8]. Such differences between the studies may be attributed to the subject population used. Regarding the WBV $+$ BFR group in the present study, the elevation in vWF response was greater than that in the WBV group. To the best of our knowledge, this is the first study to demonstrate that acute WBV $+$ BFR exercise induced an increase in vWF levels. The elevation of vWF levels following acute exercise may be indicative of vascular endothelial cell damage and platelet adhesion. Taken together, this result implies that WBV when applied with BFR would temporarily cause vascular damage and coagulation potential to a greater extent. The elevation in vWF response induced by exercise may be mediated by shear stress [12], catecholamine release [12], and adrenergic stimulation [26]. The elevated HR could be derived from raised catecholamine levels and adrenergic stimulation, consequently increasing pulsatile shear stress [14]. In the present study, the greater HR response observed in the WBV $+$ BFR group helps explain our findings of magnifying the acute response in vWF. Furthermore, as mentioned earlier, mechanical compression by BFR may also contribute to cause structural damage to the vasculature.

Elevated resting vWF levels have previously been associated with cardiovascular events [27]. However, resting vWF levels were lower in a healthy population than in patients with chronic diseases, such as diabetes and hypertension [8, 9]. Except for extreme cases [28], vWF is considered to be a biomarker of endothelial function [6, 7]. In this study, despite the elevation in vWF levels after acute WBV or WBV $+$ BFR exercise, exposure to regular WBV or WBV $+$ BFR training resulted in a similar decrease in vWF levels. The data obtained in the present study suggest that both regular WBV and WBV $+$ BFR training was equally effective in restoring and improving vascular endothelial function, which appears to elicit a beneficial effect on the endothelium of the untrained participants. This observation favours the view that regular physical exercise has a favourable effect on vascular function [29]. These results are consistent with those reported previously, which indicated vWF levels in sedentary subjects was reduced by aerobic cycling training [12], and vWF levels were found to decrease after a 7-week strenuous pre-season preparation training in elite male professional soccer players [15]. Our results are also similar to those of previous studies that demonstrated decreases in vWF levels after a 4-week stretching exercise [30], resistance exercise, aerobic exercise and resistance plus aerobic exercise in patients with coronary disease [31]. The mechanisms involved in mediating the reduction of vWF levels are not clear. It has been reported that activation of nitric oxide [30], attenuation in the production of reactive oxygen species [15, 30] and decrease in catecholamine release, which down-regulate the performance of platelet adrenergic receptors [12], may contribute to the potential adaptation in vWF response. In addition, it is worth noting that manipulating BFR to a WBV training regimen provides no additional long term effect in vWF response compared with isolated WBV training. The results did not support the experimental hypothesis that adding BFR to WBV training would demonstrate a significantly greater vWF response than that with WBV training alone. Such a finding is relatively inconsistent with a previous study that showed that vWF levels decreased only in BFR resistance training but exhibited no significant changes in the non-BFR resistance training [3]. The differences in vWF response between our findings and previous studies may be related to the exercise modality and the intensity and volume of exercise. In this study, we used WBV, whereas Shimizu et al. used typical BFR resistance training, which is the combination of 20% 1-RM resistance exercise plus BFR [3]. Shimizu et al. demonstrated that isolated resistance training failed to produce significant changes in vWF levels after 4-weeks of training [3]. However, the WBV modality applied in our study is characterised by an oscillating movement to the entire body. These gravitational fluctuations evoked by WBV can acutely increase muscle blood flow, consequently leading to optimisation of vascular function [20]. On this basis, the characteristics of WBV may leave less room for marginal improvements in vascular function when additional BFR is applied. Consequently, the magnitude of the response in vWF levels exhibited no significant differences between the WBV $+$ BFR and WBV groups.

Regarding the interpretation of the study results, there are a few limitations that need to be emphasised. First, as the participants in this study were a sedentary population, the results might not be appropriate to extrapolate to populations who are physically active. Second, the same target cuff pressure was maintained for each participant throughout the training period. Therefore, further studies are warranted to clarify whether progressive BFR would optimise the training effect.

In conclusion, although one bout of WBV $+$ BFR magnifies the vWF response compared to that with WBV alone, implying the manipulation of BFR may acutely cause vascular damage and coagulation potential to a greater extent. However, the elevation in vWF response did not progress till 8 weeks of training. After 8 weeks of training, the vWF levels were decreased and the magnitude was similar between the WBV $+$ BFR and WBV groups. It appears that both regular WBV and WBV $+$ BFR training produce an equally beneficial effect in improving vascular endothelial function in a sedentary population, regardless of the application of external BFR.