Activity-Induced Increase in Achilles Tendon Blood Flow Is Age and Sex Dependent

Abstract

Background:

Previous research of a young adult population identified a lower increase in Achilles tendon blood flow immediately after a running activity as a significant predictor for the development of Achilles tendinopathy (AT). Furthermore, advancing age is often mentioned as a risk factor for the development of AT, and the highest incidence for AT is reported to occur in middle-aged recreational male athletes.

Purpose:

To investigate the effect of age, sex, and type of physical activity on the increase in Achilles tendon blood flow.

Study Design:

Controlled laboratory study.

Methods:

Blood flow measurements of 33 subjects aged 18 to 25 years and 30 subjects aged 40 to 55 years were obtained before and after 4 physical activities performed in randomized order: running, cycling, dynamic stretching, and rope skipping. Blood flow measurements of the Achilles tendon were performed before, immediately after, 5 minutes after, and 10 minutes after the physical activities. The effect of age, sex, and physical activities on the increase in blood flow was investigated with linear mixed models.

Results:

The results of this study identified that running, rope skipping, and cycling resulted in a significant increase in tendon blood flow (P ≤ .001), whereas stretching did not. Prominent was the finding that the increase in blood flow after activity was significantly lower in the older population as compared with the younger population (P < .001). Furthermore, male participants in the older group showed a significantly lower increase in tendon blood flow than did their female counterparts (P = .019).

Conclusion:

This study identified that sex and age significantly influence the increase in blood flow after activity, possibly explaining the increased risk for AT among middle-aged recreational athletes.

Clinical Relevance:

This study possibly identified one of the mechanisms explaining why an older male population is at increased risk for developing AT. Given that the lower increase in blood flow is an identified risk factor according to previous research, preventative measures should focus on improving this blood flow during physical activity in the physically active older male population.

Registration:

NCT03218605 (ClinicalTrials.gov identifier).

Keywords

Achilles tendon blood flow physical activity sex age

Although the Achilles tendon is the largest and strongest tendon in the human body, injuries are common.³⁷ The most common Achilles tendon injury is tendinopathy.⁴ The highest incidence for Achilles tendinopathy (AT) is usually reported to occur in middle-aged recreational male athletes.^2,26,33 This is surprising since the amount of sports participation decreases with advancing age and most other sports injuries are found to occur in a younger group.³⁹ Therefore, advancing age is often mentioned as a risk factor for the development of AT.^12,25,26,44 Advancing age is commonly associated with an increased prevalence of degenerative changes in tendons, such as decreased cellularity, lack of fiber organization, and decreased vascularity.^3,26,31 It is suggested that in a hypovascular tendon, the extent of necessary matrix remodeling is restricted, which may lead to weakening of the tendon structure, causing tendinopathy.^35,36

An increase in Achilles tendon blood flow is a normal physiologic response to activity since physical activity generates an increased metabolic demand. To fulfill this increased metabolic demand, a necessary cardiovascular redistribution of blood flow to the working soft tissue is induced.¹⁵ An impaired exercise-induced transient increase in blood flow leads to inadequate tissue oxygen delivery and metabolic dysregulation.^14,20 This relates to AT given that previous research of an adolescent population identified a lower increase in blood flow immediately after a running activity as a significant predictor for the development of AT.⁴²

Given that the incidence of tendinopathy increases with age and a lower increase in blood flow immediately after activity is identified as a risk factor in an adolescent population, it is possible that this increase in blood flow after activity is altered in an older population. However, it is striking that, to date, no research has investigated whether this blood flow response after activity is age, sex, or activity dependent. Therefore, the aim of this study was to investigate the effect of age and sex on Achilles tendon blood flow after different physical activities.

Methods

This study was performed at Ghent University. Approval was obtained by the Ethics Committee of the Ghent University Hospital (EC/2013/401), and all participants signed an informed consent. This study was registered at ClinicalTrials.gov (Protocol Registration and Results System; NCT03218605). Participants were subdivided into the younger or older group. Multiple physical activities were performed on different days in a randomized order to prevent fatigue and a possible interaction among them: running, cycling, dynamic stretching, and rope skipping. Blood flow measurements of the dominant Achilles tendon were performed before, immediately after, 5 minutes after, and 10 minutes after the physical activities.

Participants

In this study, 33 subjects aged between 18 and 25 years and 30 subjects aged between 40 and 55 years participated. Participants were excluded from this study if they had a history of AT, surgery of the lower extremity, or severe trauma in the lower extremity within the previous year. All participants performed at least 1 hour of weekly sports participation and did not participate in >3 training sessions a week. This resulted in 63 included participants (31 male and 32 female), with a mean age of 34.4 years and an average weekly sports participation of 2.6 hours (Table 1).

Table 1

Patient Characteristics for the Younger and Older Group^a

	Total	Younger Group	Older Group
Age, y	34.4 ± 13.7	21.9 ± 1.7	48.2 ± 4.9
Height, m	1.74 ± 0.09	1.76 ± 0.09	1.73 ± 0.08
Weight, kg	69.9 ± 11.7	67.0 ± 8.6	73.2 ± 13.7
Body mass index, kg/m²	22.9 ± 2.9	21.6 ± 1.8	24.4 ± 3.2
Sport, h/wk	2.6 ± 1.2	3.2 ± 1.7	2.1 ± 1.0
Sex
Male	31 (49)	16 (48)	15 (50)
Female	32 (51)	17 (52)	15 (50)
Limb dominance
Right	55 (87)	31 (94)	24 (80)
Left	8 (13)	2 (6)	6 (20)

Values are presented as mean ± SD or n (%).

Study Design

Participants were instructed not to engage in any sports activities 48 hours before testing to ensure a valid measure of exercise-related increase in blood flow. Before the physical activity was performed, participants were instructed to rest on a treatment table for 10 minutes. After this resting period, blood flow was measured for a first time in prone position. Then, participants performed a physical activity (running, cycling, dynamic stretching, or rope skipping) in randomized order for 10 minutes. Immediately after this, blood flow measurements were repeated in the same prone position on the treatment table (immediate postactivity blood flow). To minimalize the transition time, the treatment table was positioned next to the area where the physical activities were performed. Next, participants were asked to rest on the treatment table while blood flow measurements were repeated 5 minutes after the physical activity. In addition, for the older population, blood flow was registered 10 minutes after the physical activity. As a consequence, 3 blood flow measurements were conducted per physical activity in the younger and older populations—preactivity blood flow, immediate postactivity blood flow, and 5-minute postactivity blood flow— with 10-minute postactivity blood flow registered only for the older population. Heart rate and rate of perceived exertion (RPE) were also measured. This test protocol was repeated for all physical activities, with a minimum 48 hours and a maximum 1 week between 2 physical activities. Participants performed all physical activities shod, wearing self-selected running shoes. Before the experimental protocol, participants were asked to fill in a questionnaire concerning demographic and anthropometric data (age, sex, height, weight, limb dominance), physical activities, and injury history.

Blood Flow Measurement

Blood flow data at the midportion of the dominant Achilles tendon were collected with the O2C device (Oxygen-to-See; LEA Medizintechnik). This noninvasive device is capable of measuring the perfusion and oxygenation of the subcutaneous tissue with an optical flat fiber probe. Measurements were performed as described by Wezenbeek et al⁴³ at a depth of 8 mm. The head of the probe was placed flat on the tissue at the measurement point, without pressure or movement. For standardization purposes, measurements were performed in a darkened room with constant temperature. The stability of the blood flow measurements has been investigated and the measurement shown to be reliable and valid.^18,43 As a measure for intraobserver reliability, a 2-way mixed single-measures intraclass correlation for absolute agreement was conducted (0.75).

Physical Activities

All activities were performed in controlled laboratory conditions (19°-21°C, 65% relative humidity) to exclude environmental influences. The younger and older populations both performed dynamic stretching, running, and rope skipping; the older population also performed cycling. These activities were performed in randomized order, and every activity was performed for 10 minutes. Heart rate was objectively measured with a heart rate monitor (Polar), as registered preactivity, immediately postactivity, and 5 minutes postactivity for all participants, as well as 10 minutes postactivity for the older population. The intensity of the exercise was subjectively monitored with an RPE scale immediately postactivity for all participants.

Running

Participants were instructed to run on a motorized treadmill (HP Cosmos Saturn) at a running pace of 2.7 m/s, without an inclination angle.^8,22

Cycling

Participants were placed on a bicycle ergometer (Ergofit Cycle 400; Gymna) with standard pedals, with the pedal bars positioned under the heads of the metatarsal bones. Participants were instructed to remain seated and generate 90 rpm to increase the muscle activity of the gastrocnemius and soleus.¹⁶ Power output was determined at 100 W.²⁹

Rope Skipping

Ninety seconds of rope skipping was alternated with 30 seconds of rest, until the total duration of 10 minutes was completed. The length of the rope was individually adjusted: from the ground to the axilla of the subject.

Dynamic Stretching

During the dynamic stretch of the calf muscles of the dominant leg, the participant performed a classic standing wall push of the nondominant leg. The participants were instructed that the endpoint of the stretch should be at the point just before discomfort and that this self-chosen distance should be reached while the dominant knee remained straight and the dominant heel remained on the floor. Once the participants had reached this stretching position, they were instructed to move up and down at a pace of 1 movement per second with the front (nondominant) knee.²⁷

Statistical Analysis

Statistical analysis was done with SPSS (v 24; IBM Corp). The effect of age, sex, and physical activities (running, cycling, dynamic stretching, rope skipping) on the increase in blood flow immediately postactivity, 5 minutes postactivity, and 10 minutes postactivity (ie, postactivity blood flow minus preactivity blood flow) was investigated with linear mixed models. Analyses were executed with participants as a random factor and with age, sex and physical activities as fixed predictors. Post hoc analyses were performed with Bonferroni corrections. The effect of possible covariates was investigated: body mass index (BMI), heart rate, RPE, and sports participation. The residuals of the linear mixed model were checked for normal distribution and homoscedasticity. The level of significance was set at α = 0.05.

Results

BMI, heart rate, RPE, and sports participation did not have an effect on the outcome parameter and are therefore not included as covariates in the analyses (for subject demographics, see Table 1).

Table 2 displays the values of the blood flow variables, expressed in arbitrary units (AUs), per activity and timing of measurement for the younger and older groups. In both age categories, no significant differences in preactivity flow were found among the activities (P = .077 and P = .484 for the younger and older groups, respectively). The immediate postactivity blood flow was significantly higher than the preactivity flow after running, rope skipping, and cycling (P < .001 for the younger and older groups after running and rope skipping and P = .001 for the older group after cycling). The tendon blood flow measured 5 and 10 minutes after running, rope skipping, and cycling was significantly higher than the preactivity flow (P < .002 for 5 and 10 minutes after running and rope skipping in both age categories; P = .043 and P = .030 for 5 and 10 minutes after cycling in the older group), but significantly lowered compared with the immediate postactivity flow (P < .001 for 5 and 10 minutes after running and rope skipping in both age categories; P = .023 and P = .025 for 5 and 10 minutes after cycling in the older group). No significant differences were found between the flow at 5 minutes postactivity and 10 minutes postactivity for any activity in the older group (P = .499). Dynamic stretching did not significantly increase blood flow immediately after activity nor after 5 and 10 minutes (P value range: .277-.566 for the younger and older groups).

Table 2

Tendon Flow Characteristics per Activity and Timing of Measurement for the Younger and Older Groups per Activity^a

	Arbitrary Units, Mean ± SD
Activity: Timing	Younger Group	Older Group
Dynamic stretching
Preactivity	57.4 ± 16.7	64.4 ± 15.0
Immediately postactivity	59.3 ± 20.0	67.2 ± 17.4
5 min postactivity	56.1 ± 15.3	66.6 ± 16.8
10 min postactivity		66.4 ± 18.7
Rope skipping
Preactivity	51.5 ± 14.8	64.2 ± 16.3
Immediately postactivity	134.1 ± 48.0	114.9 ± 46.4
5 min postactivity	72.5 ± 23.4	85.6 ± 36.3
10 min postactivity		84.8 ± 24.7
Cycling
Preactivity		65.3 ± 23.7
Immediately postactivity		81.4 ± 31.6
5 min postactivity		71.5 ± 22.3
10 min postactivity		73.5 ± 21.8
Running
Preactivity	48.5 ± 10.6	70.4 ± 19.2
Immediately postactivity	141.6 ± 48.1	119.2 ± 42.4
5 min postactivity	76.6 ± 24.8	88.7 ± 26.7
10 min postactivity		84.5 ± 27.1

Stars indicate statistical significance, P < .05.

Figure 1 displays tendon flow characteristics. In both age groups, the increase in blood flow (immediately postactivity – preactivity) is significantly higher for rope skipping and running as compared with the other activities (P < .001). Analyses between the age groups showed that the increase in blood flow (immediately postactivity – preactivity) is significantly smaller for the older group versus the younger group, as illustrated in Figure 2 (P < .001 for running and rope skipping). Also, the decrease after activity (5 minutes postactivity – immediately postactivity) is significantly smaller for the older group versus the younger group (P < .001 for running and rope skipping). The increase in blood flow 5 minutes after activity (5 minutes postactivity – preactivity) showed no significant difference between the age groups (P = .333 for running and rope skipping).

Table 3 shows the values of the RPE and heart rate (bpm) per activity and the timing of measurement for the younger and older groups. In both age categories, no significant differences in preactivity heart rate were found among the different activities (P = .314 and P = .122, for the younger and older groups, respectively). The immediate postactivity heart rate was significantly higher than the preactivity heart rate after all the performed activities (P < .001 in both age categories). The heart rate measured 5 and 10 minutes postactivity was significantly lower than the immediate postactivity heart rate after all the performed activities (P < .001 in both age categories). In both age categories, the increase in heart rate (immediately postactivity – preactivity) is significantly higher in rope skipping and running as compared with the other activities (P < .001). Analyses between the age categories showed no significant differences in increase in heart rate (immediately postactivity – preactivity) (P = .180 for running and rope skipping). Also the decrease in heart rate after activity (5 minutes postactivity – immediately postactivity) showed no significant differences between the age categories (P = .176 for running and rope skipping).

Table 3

HR and RPE per Activity and Timing of Measurement for the Younger and Older Groups per Activity^a

	Younger Group		Older Group
Activity: Timing	RPE	HR	RPE	HR
Dynamic stretching
Preactivity		74.1 ± 9.5		67.5 ± 10.0
Immediately postactivity	9.8 ± 2.2	96.3 ± 16.0	7.9 ± 1.6	79.5 ± 10.9
5 min postactivity		75.5 ± 10.0		65.1 ± 8.4
10 min postactivity				63.2 ± 8.6
Rope skipping
Preactivity		76.6 ± 12.5		69.3 ± 10.0
Immediately postactivity	14.8 ± 2.1	161.1 ±18.9	14.9 ±2.0	156.2 ± 14.5
5 min postactivity		98.2 ± 10.3		95.2 ± 9.9
10 min postactivity				87.6 ± 11.5
Cycling
Preactivity				68.7 ± 10.6
Immediately postactivity			11.4 ±2.6	127.6 ± 24.0
5 min postactivity				80.3 ± 15.8
10 min postactivity				75.7 ± 13.5
Running
Preactivity		72.7 ± 9.7		72.2 ± 9.8
Immediately postactivity	13.6 ± 2.3	149.1 ±24.2	13.7 ±1.9	156.9 ± 20. 8
5 min postactivity		94.1 ± 11.2		90.8 ± 11.9
10 min postactivity				85.8 ± 11.1

Stars indicate statistical significance, P < .05. HR, heart rate; RPE, rate of perceived exertion.

BMI, heart rate, RPE, and amount of sports participation did not have a significant effect on the increase in tendon blood after activity and were therefore not included as covariates in the analyses. Sex did significantly influence the increase in tendon blood flow after activity but only in the older population (P = .019). Figure 2 demonstrates the increase in tendon blood flow (immediately postactivity – preactivity) after rope skipping and running per age category for male and female participants. As illustrated, no significant difference in increase in blood flow was found between male and female participants in our young population, whereas the male participants in the older population showed a significantly lower increase in tendon blood as compared with the female participants.

Table 4 presents the effects of physical activities, age categories, and sex on the increase in blood flow after activity (immediately postactivity – preactivity).

Table 4

Effect of Age Categories, Activities, and Sex on the Increase in Blood Flow After Activity

	b	SE	P Value	95% CI
Intercept	54.50	6.07	<.001	42.48 to 66.51
Age,^a 18-25 y	24.36	5.72	<.001	12.95 to 35.77
Activity^b
Dynamic stretch	−70.55	6.07	<.001	−82.55 to −58.55
Rope skipping	−5.26	6.05	.385	−17.21 to 6.68
Cycling	−44.06	7.90	<.001	−59.68 to −28.44
Female sex^c	10.67	5.41	.054	−0.18 to 21.51

Older age (40-55 years) is the reference category.

Running is the reference category.

Male is the reference category.

Discussion

The results of this study identify that running, rope skipping, and cycling resulted in a significant increase of tendon blood flow. Prominent was the finding that the increase in blood flow after activity is significantly lower in the older population as compared with the younger population. Furthermore, male participants in the older group showed a significantly lower increase in tendon blood flow than did their female counterparts.

Effect of Age on Achilles Tendon Blood Flow

The results of this study show that the increase in blood flow after activity is lower in the older population versus the younger group. This is an important finding, since previous research showed that the lower the increase in blood flow after physical activity, the higher the hazard for developing AT.⁴² Therefore, this lower increase in blood flow after activity places the older population at higher risk for the development of AT, possibly explaining the higher incidence of AT among middle-aged athletes.

It is well established that physical activity generates an increased metabolic demand. To fulfill this increased metabolic demand, a necessary cardiovascular redistribution of blood flow to the working soft tissue is induced.¹⁵ Consequently, an increase in Achilles tendon blood flow as a normal physiologic response to activity was observed.³⁴ This exercise-induced transient increase in blood flow is primarily due to a local vasodilatory response that serves as a feedforward mechanism for exercise hyperemia.¹³ With advancing age, the normal regulation of exercising blood flow is impaired in the skeletal muscles. The age-associated impairments in vascular conductance are thought to be the result of vascular stiffness and impaired local vasodilatory or vasoconstrictor signaling.²⁰ This impaired exercising muscle blood flow leads to inadequate tissue oxygen delivery and metabolic dysregulation.^14,20 This is important since metabolic disorders have paramount relevance to the progression of tendon damage.¹

As stated, the results of this study demonstrate that the increase in blood flow after activity is lower in the older population as compared with the younger group. This finding is in accordance with the study of Langberg et al,²⁴ who found nonsignificantly lower peritendinous absolute flow in a middle-aged population versus a younger group after a static calf muscle exercise. Previous research in the Achilles tendon found an association between a decrease in microcirculation and the onset of tendon degeneration.¹⁷ Furthermore, this decreased vascularity is thought to cause decreased tensile strength or to indirectly weaken the tendon through degenerative changes and structural vulnerability with decreased healing potential.^28,36,40 Therefore, it is plausible that this age-induced lower increase in blood flow after activity and possibly resultant altering of metabolic properties lead to weakening of the normal tendon structure and eventually AT.

Clinical consequences are that this study possibly identified one of the mechanisms why an older male population is at increased risk for developing AT. Given that the lower increase in blood flow was identified as a risk factor in previous research, it seems logical that the increase in blood flow during activity should be stimulated in an older population. Previous research stated that prostaglandins, nitric oxide, heat, massage, vibration techniques, and longer warm-up elevate blood flow. However, further research is needed to investigate the vascular response of these latter techniques in the Achilles tendon, since the current literature is mainly limited to changes in blood flow in the skin surface.⁴² In addition, further research should focus on investigating strategies to modify this diminished vascular response to activity in the Achilles tendon. The effect of training programs on the vascular response to activity in tendons should be investigated because physical activity has the potential to offset the age-related decline in blood flow in skeletal muscles during exercise, thereby improving oxygen delivery and an enhanced energy production from oxidative metabolism. This effect was shown in skeletal muscles after a period of aerobic high-intensity exercise training,^6,32 but to the best of our knowledge, this has not yet been studied in tendons.

Effect of Sex on Achilles Tendon Blood Flow

Next, this study found that male participants in the older population showed a lower increase in tendon blood flow versus the females in this age group. The lower increase in tendon flow after activity among the male participants in the older population is in agreement with previous research stating that male sex and advancing age are associated with diminished tendon blood flow. This was investigated with laser Doppler flowmetry in the assessment of Achilles tendon blood flow among 75 participants.⁵ Furthermore, previous research studied the effect of estrogen on the peripheral blood flow and found a significant increase in blood flow associated with a reduction of vascular resistance, explaining some of the beneficial effects of estrogen on the vascular system.⁴¹ The results of this study might explain the higher incidence of AT found among male middle-aged athletes.^5,26 However, it should be considered that differences in physical activity between male and female athletes make it difficult to evaluate the independent effect of sex on Achilles tendon blood flow, since no previous study investigated sex as an independent risk factor per amount of sports participation (eg, 1000 hours). The logical clinical implication is that middle-aged men with a lower increase in blood flow after physical activity need more emphasis on warm-up to improve the vascular response to activity and consequently reduce their risk for developing AT.

Effect of Activities on Achilles Tendon Blood Flow

Running, rope skipping, and cycling resulted in an increase of tendon blood flow, and this increase after running and rope skipping was significantly higher as compared with cycling. In addition, the results of this study identified that dynamic stretching did not significantly alter Achilles tendon blood flow. An explanation for the induced increase in tendon blood flow after running, rope skipping, and cycling is that these activities are dynamic exercises that require contraction and relaxation of the working tissue. This is directly related to physiologic processes, such as an increase in body temperature and the metabolic rate of the working tissue, that lead to vasodilation of the blood vessels in the working soft tissues and subsequently to an increase in blood flow.^{11,15,19,21,23,34,38} The lower increase in blood flow observed after cycling versus rope skipping and running is unsurprising and in agreement with previous research observing a lower total limb blood flow immediately postexercise in cycling over running. Millet et al³⁰ explained this by differences in muscle pump efficiency, exercise position, and differences in type of muscle contraction between the exercises. Furthermore, during exercise, skeletal muscle blood flow was shown to increase with higher workload,⁹ and the workload during running is higher than that during cycling.⁷

Methodological Considerations

Several limitations of this study are noteworthy. First, our study was performed on a healthy population. Therefore, our results cannot be generalized to pathologic tendons. Next, the study design of the older population was more extensive since cycling and the blood flow measurement 10 minutes after activity was added to the protocol used in the younger population. Since this younger population was tested first, preliminary analysis showed a decrease in blood flow 5 minutes after physical activity but the further course of the blood flow remained unclear. In addition, cycling was added for the comparison of the vascular response to a non-weight bearing physical activity with working muscle pump to be able to interpret the results more profound. Therefore, the cycling activity and the measurement 10 minutes after physical activity were added to the study design of the later tested older age group. We are aware that this is a limitation of this study. Nevertheless, we believe that adding cycling and the extra blood flow measurement ensured a more correct and more extensive interpretation and discussion of the results. Also, given the known association between the increase in Achilles tendon blood flow and tendon degeneration, measuring tendon structure would have given this study an added value. Another limitation of this study is that no ultrasound imaging of the tendon nor detection of possibly present neovascularization was performed to exclude or include participants. In this study, we used O2C to perform the blood flow measurements. There is no gold standard for measuring blood flow,¹⁰ and this noninvasive device has been shown to be valid and reliable.^18,43

Despite several limitations, this study is the first to investigate the effect of age and sex on Achilles tendon blood flow after different physical activities performed in randomized order.

Conclusion

This study is the first to investigate the effect of age and sex on Achilles tendon blood flow after different physical activities. The results showed that the increase in Achilles tendon blood flow during physical activity is lower in an older population and that the male participants in the older population had a lower increase in tendon blood flow as compared with their female counterparts. Furthermore, the increase in Achilles tendon blood flow was activity dependent, with running and rope skipping resulting in the highest increase in blood flow, followed by cycling. Stretching did not alter Achilles tendon blood flow.

Footnotes

The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

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