The responses of glabrous and nonglabrous skin microcirculation to graded dynamic exercise and its recovery

Abstract

This study investigated the responses of skin blood flow (SkBF) in glabrous and nonglabrous skin to graded submaximal dynamic exercise and its recovery. We enrolled eight healthy young men with comparable maximal oxygen uptake (V_O2max). Laser-Doppler flux (LDF) was assessed on the finger pulp (glabrous site) and the volar forearm (nonglabrous site) simultaneously with skin temperature, heart rate and blood pressure; cutaneous vascular conductance (CVC) was calculated. Subjects were monitored before (baseline), during and 25 minutes after incremental cycling. CVC in the pulp decreased with the onset of exercise (0.53±0.09AUmmHg^–1 vs. baseline 1.23±0.25AUmmHg^–1, p = 0.006), and persisted low until exercise cessation, whereas CVC in the forearm started to increase at 60% of subjects’ V_O2max, attaining its maximum at the highest exercise load (0.44±0.11AUmmHg^–1 vs. baseline 0.12±0,03AUmmHg^–1, p = 0.017). In the recovery, CVC in the pulp attained a higher plateau value compared to baseline (1.51±0.22AUmmHg^–1, p = 0.021), interrupted by abrupt transient falls of CVC. On the forearm, CVC subsequently returned to its baseline. SkBF of glabrous and nonglabrous sites adjust in an opposite manner to graded exercise load and also differ during recovery.

Keywords

Skin microcirculation laser Doppler fluxmetry arterio-venous anastomoses submaximal graded exercice recovery to exercise glabrous skin nonglabrous skin cutaneous vascular conductance

1 Introduction

During exercise, the primary challenge of the cardiovascular system (CVS) is to deliver blood to active muscles to meet their metabolic needs. However, there are other regulatory demands, such as maintenance of blood pressure and body temperature that compete for blood flow during muscular work. The physiological integration of these conflicting demands is reflected in the changed distribution of blood flow to special circulations during exercise to meet optimal conditions for exercising [31]. The cessation of exercise with a sudden fall of metabolic needs, lost muscle pump, residual heat to be eliminated, etc. confers new challenges to the CVS. To fulfill these, blood flow is again redistributed during recovery period to prevent syncope and eliminate excessive heat until resting state is reached [16]. A particular target for an integrative regulation of blood flow during and after exercise is the cutaneous circulation [18].

Skin is under constantly competing thermoregulatory and nonthermoregulatory demands [5, 27]. Besides from sweating, heat balance in the human body is maintained by changes in the rate of heat loss via adjustments of cutaneous vascular conductance (CVC). During dynamic exercise, the production of heat in the working skeletal muscles increases tremendously and thermoregulatory reflexes induce a decrease of vascular tone in the skin: Skin blood flow (SkBF) during extreme exercise in a hot environment can attain up to 7 L/min as compared to 300 mL/min at rest in thermoneutral conditions [19, 20]. Independent of thermal control, there is a demand for maintaining blood pressure affecting SkBF [18]. Apart from baroreflex [16], metaboreflexes and mechanoreflexes of active skeletal muscles play a role in modulating SkBF during exercise and in the subsequent recovery [7 , 43].

The peculiarity of skin microcirculation is the dual control of its vascular tone: While acral glabrous areas (such as the finger pulp) of the skin are mainly under the influence of the sympathetic noradrenergic vasoconstrictor system [39], the nonglabrous areas (such as the volar forearm) are additionally innervated by sympathetic cholinergic vasodilatory nerve fibers with a yet unidentified transmitter; a range of mediators have been proposed [5 , 25]. Finally, the contribution of local factors such as endothelial vasodilators to the regulation of vascular tone should not be underestimated [26 , 48]. Special anatomical features of acral glabrous areas are arteriovenous anastomoses (AVAs), which when open are the main structural channels for heat elimination [3 , 38]. Additionally, it is assumed that the large variations in CVC observed in glabrous skin at rest represent AVAs’ function [3, 42].

Different vascular responses to exercise with respect to measuring skin site have been reported [29 , 50]. Saad et al. [42] showed that static isometric exercise elicits a reduction of CVC accompanied by a decrease in the fluctuation of SkBF in glabrous parts, while the CVC in nonglabrous sites did not change, and concluded that the AVAs have more sustained vasoconstrictor tone during isometric exercise than at rest. Yamazaki [47] found an increased amplitude of CVC response to sinusoidal exercise in the palm compared to the forearm as well as different phase lag of CVC in both skin sites. In another study, Yanagimoto el al. [50] reported that during short-term (60 s) dynamic exercise, CVC in both, glabrous and nonglabrous areas decreased with increasing exercise intensity.

It has been established that the threshold at which nonglabrous SkBF begins to rise, increases with the intensity of exercise [5, 21]. Furthermore, there are regional differences in the threshold for vasodilation in response to an increase in exercise intensity [27, 29].

Recovery from dynamic exercise is associated with significant cardiovascular and thermoregulatory adjustments that affect skin blood flow through several modifications of the vasoconstrictor and active vasodilator system [4 , 46]. Studies have also shown that the contribution of the above-mentioned reflexes to the regulation of SkBF in the recovery period is strongly dependent on the mode of recovery: During inactive recovery, baroreflex appears to be primarily involved, while muscle pump and central command during active recovery diminish the baroreflex demand [4 , 22].

As the results of the above mentioned studies are inconsistent, it is obvious that the regulation of SkBF during and following exercise is a complex phenomenon integrating vasoactive adjustments of different skin vascular structures (AVAs, capillaries) to central and local stimuli. To the best of our knowledge, there are no available studies on the impact of exercise load on SkBF during graded submaximal dynamic exercise and no reports on the response of glabrous skin microcirculation in the recovery.

Accordingly, the aim of our study was to evaluate the response of SkBF, CVC and skin temperature (T) on the finger pulp (glabrous site) during submaximal incremental cycling and in the subsequent inactive recovery and to compare it with the simultaneously measured response on the volar forearm (nonglabrous site). Simultaneously, heart rate (HR) and mean arterial pressure (MAP) were assessed.

2 Methods

2.1 Subjects

Following ethical approval from the National Ethics Committee, eight healthy, physically active young men, non-smokers, with comparable maximal oxygen uptake (V_O2max) were recruited toparticipate in the study. Written informed consent was obtained from each and the study was conducted in accordance with the Helsinki Declaration. Subjects were 20.8±0.4 years old, their body mass index (BMI) was 23.58±0.52 kg/m² and their V_O2max 54.85±2.00 mL kg^–1 min^–1, as estimated indirectly using the Astrand and Ryhming nomogram for graded cycling [2].

2.2 Experimental procedure

Subjects arrived at the laboratory at 11 a.m. after abstaining from alcohol and caffeine consumption for at least eight hours; a light breakfast early in the morning was allowed. They were asked to avoid physical activity for 48 hours before testing. Their approximate maximal HR (HR_max) was estimated using a “220 - years of age” formula and HR corresponding to the 85% HR_max was used as a target HR value.

At the arrival to the laboratory, subjects changed to shorts and athletic shoes. Experiment took place in a quiet and comfortable place with ambient T of 23°C and relative humidity of 60%, after 20 min of acclimatization, during which the subjects were instrumented with the measuring devices. Measurements were performed for 5 minutes in a supine position. Afterwards, subject mounted a cycle ergometer (Ergoline, Germany), and his right arm and hand were placed into the arm rest to avoid movement artifacts during exercise and to match the heart level. The left hand was left free to hold the handle bar. We assumed that the cardiovascular system adjusted to the new posture in 10 minutes. After 5 minutes of recording in the sitting resting position to obtain baseline values, the exercise protocol commenced. It consisted of graded cycling and a subsequent 25-min inactive recovery period as described in our previous study [8]. Subjects cycled on cycloergometer starting at 40W, the workload was increased in steps of 50W every 3 minutes till the target HR was reached with no rest between the cycling bouts. The pedaling rate was kept constant at 60 rpm for small workloads and was increased spontaneously for workloads greater than 200W, in accordance with the cycle ergometer built-in protocol for high loads. Immediately after the target HR was reached, subjects were asked to stop cycling and remained seated at rest on the cycle ergometer for 25 minutes in the recovery period avoiding any movements. All measured parameters were recorded during stepwise exercise and in the recovery period without interruption.

2.3 Measurements

The surface electrocardiogram (ECG) was monitored using a conventional ECG apparatus to determine HR and beat to beat R-R interval duration (RR) from lead II. Arterial blood pressure (BP) was measured continuously by the Finapres 2300 (Ohmeda, USA) at the middle digit of the right hand, fixed at the heart level. SkBF was estimated by assessing laser Doppler flux (LDF) on the representative measuring sites, simultaneously with the corresponding T measurement (PeriFlux System 5000, PF 5001 main control unit, PF 2010 LDPM and PF 2020 Temp Unit, Perimed, Stockholm, Sweden). LDF was expressed in arbitrary perfusion units (AU). The principles of laser Doppler (LD) blood perfusion monitoring and the limitations of the method are described elsewhere [23 , 40]. Two LD probes were attached to the skin to an area without visible vessels, the first one to the pulp of the right index finger representing glabrous skin and measuring pulp LDF and the second one to the right volar forearm representing nonglabrous skin, measuring forearm LDF. Subjects were instructed to relax their right arm during measurements, especially during exercise. The T probes were fixed to the same spots under the LD probe holder. CVC was calculated as the ratio of LDF to MAP for the glabrous (pulp CVC) and for the nonglabrous (forearm CVC) skin. CVC data are presented in AUmmHg^–1 or relative to the baseline value at the resting sitting position.

2.4 Data acquisition and statistical analysis

The output signals of the lead II of ECG, Finapres and PeriFlux were digitalized at a sampling rate of 500 Hz using a DI-720 Series analog-to-digital converter, recorded and analyzed with DATAQ Instruments acquisition and analysis software. To determine RR and MAP, the Nevrokard (Medistar, Slovenia) software was used.

During graded exercise, data were averaged over the last minute of exercise at each workload, when the cardiovascular system was assumed to reach a new steady state, being adapted to the particular workload. During recovery period, data were averaged over 5-minute intervals. The data are presented as the mean values±standard error of means (SEM). All values obtained during and after exercise were compared to the resting sitting values by a one way ANOVA for repeated measurements (Dunnett’s test). The differences of the measured parameters between different phases of the response to our protocol were tested by a paired t-test. We performed paired student t-test to find the differences between glabrous and nonglabrous skin sites. Significance was accepted at p ≤0.05.

3 Results

3.1 Baseline values

The values of the measured parameters recorded in the sitting position at rest were taken as baseline values: RR 847.20±33.08 ms, MAP 98.86±4.88 mmHg, pulp LDF 116.65±20.76 AU, pulp CVC 1.23±0.25 AUmmHg^–1, pulp T 32.05±0.68 °C, forearm LDF 11.64±2.21 AU, forearm CVC 0.12±0.03 AUmmHg^–1 and forearm T 32.80±0.34 °C.

Both, the LDF and CVC baseline values significantly differed between the pulp and the forearm (p < 0.0001 for LDF and CVC), whereas there was no significant difference in the skin T between both measuring sites (p = 0.34).

3.2 Response to exercise

The predicted target HR of all subjects was 169.3±0.4 min^–1. The subjects reached their own target HR at 240 W (n = 6) or at 290 W (n = 2); the mean cycling duration was 14.85±0.25 min.

Figure 1 shows a typical response to the protocol in one subject that can be divided in two parts: The response during exercise and the response in the recovery.

3.2.1 Response during exercise

Figure 2 depicts the response of RR (A), MAP (B), CVC (C-pulp, D-forearm), LDF (E) and skin T (F) to the protocol. With each consecutive exercise load there was a consistent and significant reduction in the RR (Fig. 2A) associated with a significant increase in BP (Fig. 1) and MAP (Fig. 2B). The HR variability decreased with increased load (Fig. 1).

LDF, CVC and the corresponding skin T of the same skin spot changed in parallel throughout graded exercise. We found opposite responses to graded dynamic exercise in the glabrous and nonglabrous skin, i.e., falling of LDF, CVC and skin T in the former and rising in the latter skin spot, respectively (Figs. 1, 2C, 2D, 2E, 2F). Compared to sitting rest, the pulp LDF (56.31±8.65 AU, p = 0.005), CVC (0.53±0.09 AUmmHg^–1, p = 0.006,) and skin T (30.81±0.74 °C, p = 0.001) decreased significantly at the onset of exercise (load = 40 W) and persisted significantly decreased at all loads(Figs. 2C, E, F). There were no significant differences in the responses in glabrous LDF and CVC with respect to exercise load.

In contrast, the forearm LDF and CVC increased consistently with an increased load, not significant during the first two exercise bouts but significant at 60% of the subjects’ V_O2max (28.08±8.59 AU, p = 0.043 and 0.25±0.09 AUmmHg^–1, p = 0.042, respectively) (Figs. 2D, E). The forearm skin T increased slightly with graded exercise load but reached significance only at the highest exercise level (34.37±0.59 °C, p = 0.047) (Fig. 2F).

Comparing glabrous and nonglabrous skin, LDF and CVC significantly differed during the first three loads of exercise (p < 0.0001 for LDF and CVC at 40 W; p = 0.002 for LDF and p = 0.007 for CVC at 90 W; p = 0.033 for LDF and p = 0.046 for CVC at 140 W), (Figs. 1, 2E), whereas the difference disappeared at higher loads (p = 0.751 for LDF and p = 0.850 for CVC at 190 W; p = 0.524 for LDF and p = 0.502 for CVC at 240 W) while the skin T difference was significant at this point (5.85±1.54°C, significantly higher at the forearm, p < 0.0001) (Fig. 2F).

At the end of exercise, RR was 360.6±2.7 ms and MAP 138.8±5.1 mmHg. The pulp LDF (46.26±9.86 AU) and CVC (0.34±0.08 AUmmHg^–1) reached their minimum values by the end of exercise, whereas the forearm LDF (58.21±15.19 AU) and CVC (0.44±0.11 AUmmHg^–1) attained their maximum at this point. The pulp CVC was only one third of its baseline value, whereas the forearm CVC was nearly four times greater than its pre-exercise sitting value.

3.2.2 Response in the recovery

The onset of recovery after graded dynamic exercise was marked with a prominent RR increase and an abrupt fall of MAP from 138.8±5.1 mmHg to 113.29±4.45 mmHg (p < 0.001) (Fig.1).

After these transient changes, all measured parameters approached their baseline, pre-exercise values (Fig. 1). The major changes occurred within the first five minutes after the cessation of exercise (early recovery period) and were minimized in the late recovery period (after the 5th minute of recovery). In general, during recovery the LDF, CVC and T of the same skin site changed in parallel, with an exception: During the first 31.36±3.24 s after the cessation of exercise, the pulp LDF and CVC rose while the pulp T remained constant (Fig. 1).

In early recovery, MAP remained nearly stable, whereas RR continued to rise. The pulp LDF increased in parallel with RR, the slope of the pulp LDF increase was 3.32±0.27 AUs^–1. The corresponding skin T was constant (28.76±0.69 °C) for nearly half a minute after the cessation of exercise. Thereafter, the pulp skin T started to rise at a rate of 0.01 °Cs^–1, while the pulp LDF continued to increase even though 10 times slower than at the beginning of the early recovery (0.31±0.16 AUs^–1). CVC changed in parallel with LDF. The forearm LDF, CVC and T decreased simultaneously.

In late recovery, some of the parameters returned to their baseline value, reaching it by the end of the experiment (MAP, forearm LDF, forearm CVC and forearm T), while others (RR, pulp LDF, pulp CVC and pulp T) attained a significantly higher plateau values (669.98±30.63 ms, p < 0.0001; 156.86±19.92 AU, p = 0.0018; 1.51±0.22 AUmmHg^–1, p = 0.0296 and 33.73±0.36 °C, p = 0.0238, respectively) (Fig. 2) compared to the baseline.

A striking feature of the responses in glabrous LDF and CVC was a sudden onset of marked transient falls approximately 2 minutes after exercise cessation that were markedly expressed throughout the remaining recovery period.

At the end of the experiment, both, the LDF and CVC values significantly differed between the pulp and the forearm (p < 0.0001 for LDF and CVC) whereas there was no significant difference in the skin T between both measuring skin sites (p = 0.2924).

4 Discussion

Our study aimed at tracing the responses of glabrous and nonglabrous skin to submaximal graded dynamic exercise simultaneously with some other cardiovascular parameters. The responses of the pulp LDF and CVC distinctly differed from the responses of LDF and CVC on the volar forearm during exercise as well as in the recovery, implying different mechanisms of vasomotor control. CVC in the pulp decreased with increasing load reaching the lowest value at exercise cessation whereas CVC in the forearm started to increase at 60% of subjects’ V_O2max attaining its maximum at the highest exercise load. The main finding of the present study is a specific pattern of the pulp CVC in the recovery that has so far not been described in any other available study. The pulp CVC increased rapidly after exercise cessation to a higher value compared to pre-exercise and persisted as a plateau throughout recovery. Furthermore, in the recovery, abrupt transient falls of LDF and CVC appeared in glabrous skin, potentially reflecting the closing of AVAs. As CVC in the forearm decreased after exercise cessation, we might speculate that nonglabrous areas are the main skin sites for heat elimination during exercise, whereas glabrous areas overtake the thermoregulatory role in the recovery.

Our results showed a substantial decrease of SkBF and CVC in the finger pulp during graded dynamic exercise and an increase of SkBF and CVC in the volar forearm. Regarding the finger pulp, Midttun and Sejrsen [38] used the heat washout method and showed an instantaneous decrease in SkBF in the thumb as a response to moderate bicycle exercise followed by an increase to the resting level after 46 minutes of exercise. Similar trend of decreased CVC in the palm at the very beginning of exercise was observed by Yamazaki [47]. Different behavior of the responses later during exercise might be the result of different mode and intensity of exercise applied [47]. Since blood vessels of the finger pulp are innervated mainly by the sympathetic vasoconstrictor fibers [39], the fall of CVC in the finger pulp might be explained by an increase in the sympathetic tone during exercise that could indirectly be implicated from simultaneous increase of HR and MAP shown in our study. Also, the fluctuations of CVC in the pulp diminished during exercise, accordingly with the finding of Saad et al. who proposed that the blood flow through AVAs decreased with exercise [42]. During thermoneutral resting conditions, AVAs that are present in glabrous skin show marked fluctuations of blood flow reflecting their synchronous closing and opening due to bursts of efferent sympathetic impulses [3]. These fluctuations are abolished when AVAs remain mainly closed or mainly opened [3].

Contrary to the pulp, SkBF in the the volar forearm started to rise during exercise in our study. The increase of LDF during exercise is in accord with some other studies that assessed SkBF in the volar forearm during exercise [10 , 38]. As these areas receive vasoconstrictor and vasodilator fibers, the increase of CVC which became significant at a workload of about 60% V_O2max, might reflect the activation of vasodilator fibers.

While most other studies focused on nonglabrous areas [15 , 46] during recovery, our study is the first that also assessed the response of the pulp SkBF. The rapid increase of the pulp LDF and CVC along with the increase of RR early in the recovery after the cessation of exercise might imply sympathetic withdrawal and consequent release of vascular tone [15]. Contrary to the pulp LDF, the pulp skin T remained unchanged for a while; subsequently, also the pulp T started to increase. We found this phenomenon very interesting as it was observed only in this very phase. A similar phenomenon of independent LDF and T action has not been described elsewhere. We might explain the delay of the pulp T increase with respect to the pulp LDF by the time needed for heat to be transferred from the cutaneous blood vessels’ pool in the pulp to the surface of the skin. Factors, such as thickness of the subcutaneous tissue as well as heat conductance of the skin could impact the conduction of the heat. One might argue that the delay could be a consequence of the time characteristics of the temperature-measuring device, but because the same phenomenon was not observed at any other sites or in any other phases this argument seems less probable.

Since nonglabrous areas also receive vasodilator fibers, the decrease in the forearm LDF and CVC after exercise cessation might be a reflection of a partial withdrawal of this vasodilator tone. Indeed, it has been shown that active cutaneous vasodilation is modified by baroreflex in the recovery [35]. SkBF, CVC and skin T subsequently returned to the baseline, pre-exercise sitting values on the volar forearm.

Later in the recovery, the pattern of most haemodynamic variables resembled that of the resting conditions, while the increased LDF and CVC far above the resting level persisted in the pulp, presumably as a consequence of open AVAs. Since AVAs are the main vasoconstrictor target during exercise [42], we can speculate that the increase of the pulp LDF and CVC after exercise cessation could be the consequence of AVAs’ reopening. High plateau values of the pulp LDF and CVC with minimal time oscillations early in the recovery could be associated with synchronous opening of AVAs, in order to emitting residual heat. This notion is supported by the finding that fluctuations in SkBF are abolished when AVAs remain mainly opened [3]. In this period, marked transient drops of the pulp CVC and LDF almost to zero appeared. They might reflect the synchroneous closing of AVAs to redirect SkBF to the nutritive capillaries and thus prevent them from being unnourished.

Increased LDF in the pulp throughout the recovery (25 minutes) might reflect the need to eliminate additional heat in order to achieve thermoneutral condition; in this scenario, the core T would still remain elevated but not to the threshold needed to activate the vasodilatory fibers innervating the volar forearm. In the light of the remaining increase of CVC, LDF and T in the pulp, we might assume that glabrous areas play an important role in thermoregulation in the recovery. We can only speculate about the underlying mechanisms of increased LDF in the pulp. Apart from the sympathetic withdrawal, the endothelium-dependent vasodilation might play a role; augmented shear stress due to increased blood flow stimulates the release of endothelial vasodilators that subsequently increase SkBF [13 , 48]. The steep slope of the pulp LDF increment with no visible fluctuations at the beginning of recovery might reflect the endothelial component. The impact of local skin T and thermoreflexes could also be taken into account [9 , 27]. Implication for local thermal mechanisms could be deduced from the study of Hales et al. [14] where the authors proposed that local T strongly impacted glabrous areas during a thermoregulatory challenge. Last but not least, apart from differences in the innervation, the different responses of glabrous and nonglabrous LDF and CVC might be the result of a presynaptic modification of vasomotor reflexes. For example, NO has been shown to be able to modify the release of noradrenaline from the presynaptic nerve endings [44]. Also, the sensitivity of vascular smooth muscle cells to neural or local stimuli might be different in these two areas [15].

Some limitations of the study should be considered. As we did not apply any inhibitors of vascular tone mediators, speculation on the potential mechanisms involved can be drawn only on the basis of previous reports. An application of bretylium [20, 27] might have revealed the potential involvement of vasodilatory fibers, whereas the blockade of endothelial vasodilators would demonstrate the endothelial contribution. Furthermore, the determination of core T would have been of great usefulness in establishing the threshold for vasodilation and explaining the alterations in skin T and LDF. A determination of sweat rate at different measuring sites would have enabled a better discrimination of the mechanisms involved. By enrolling only young men with comparable V_O2max in the study as well as performing the study on the same time of the day, we were trying to eliminate the impact of age [17, 28], gender [11 , 33], fitness level [28 , 45] and circadian variability [1] on the cardiovascular control.

In conclusion, our study has confirmed that SkBF of glabrous and nonglabrous areas adjust in an opposite manner to graded exercise load and also differ during recovery. We might speculate that nonglabrous areas are the main skin sites for heat elimination during exercise, whereas glabrous areas overtake the thermoregulatory role in the recovery. Namely, the increased CVC and skin T in glabrous parts persisted at least 25-minutes in the recovery, whereas it returned to the baseline level in nonglabrous parts by that time. Glabrous CVC response reflects the blood flow through AVAs. The transient falls of CVC in the pulp in late recovery might reflect the closing of AVAs to redirect blood flow to the nutritive capillaries.

Further studies are needed to explain the mechanisms of different responses, elucidating the impact of sympathetic nervous system and endothelium. Particular focus should be addressed on the role of increased glabrous SkBF in the recovery and to elucidate to which extent it could be ascribed to thermoregulation. Also, the characteristic falls in SkBF should be clarified: Is it merely the need to redirect flow to the nutritive capillaries or do they serve some other purpose?

Footnotes

Acknowledgments

We would like to thank to all volunteers who participated in the study.

Financial support for the study was provided from Ministry of Education, Science and Sports, Republic Slovenia (Grant No.P3-0019).

The authors declare no conflict of interest.

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