Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.

In Cardiac Patients ß-Blockers Attenuate the Decrease in Work Rate during Exercise at a Constant Submaximal Heart Rate.

PURPOSE: Exercise prescription based on fixed heart rate (HR) values is not associated with a specific work rate (WR) during prolonged exercise. This phenomenon has never been evaluated in cardiac patients and might be associated with a slow component of HR kinetics and ß-adrenergic activity. The aims were to quantify, in cardiac patients, the WR decrease at a fixed HR and to test if it would be attenuated by ß-blockers. METHODS: Seventeen patients with coronary artery disease in stable conditions (69 ± 9 yr) were divided into two groups according to the presence (BB) or absence (no-BB) of a therapy with ß-blockers, and performed on a cycle ergometer: an incremental exercise (INCR) and a 15-min "HR CLAMPED " exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to the gas exchange threshold +15%. HR was determined by the ECG signal, and pulmonary gas exchange was assessed breath-by-breath. RESULTS: During INCR, HR peak was lower in BB versus no-BB ( P < 0.05), whereas no differences were observed for other variables. During HR CLAMPED , the decrease in WR needed to maintain HR constant was less pronounced in BB versus no-BB (-16% ± 10% vs -27 ± 10, P = 0.04) and was accompanied by a decreased V̇O 2 only in no-BB (-13% ± 6%, P < 0.001). CONCLUSIONS: The decrease in WR during a 15-min exercise at a fixed HR (slightly higher than that at gas exchange threshold) was attenuated in BB, suggesting a potential role by ß-adrenergic stimulation. The phenomenon may represent, also in this population, a sign of impaired exercise tolerance and interferes with aerobic exercise prescription.

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte P O 2 ${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

Decrease in work rate in order to keep a constant heart rate: biomarker of exercise intolerance following a 10-day bed rest.

Aerobic exercise prescription is often set at specific heart rate (HR) values. Previous studies demonstrated that during exercise carried out at a HR slightly above that corresponding to the gas exchange threshold (GET), work rate (WR) has to decrease in order to maintain HR constant. We hypothesized a greater WR decrease at a fixed HR after simulated microgravity/inactivity (bed rest, BR). Ten male volunteers (23 ± 5 yr) were tested before (PRE) and after (POST) a 10-day horizontal BR and performed on a cycle ergometer 1) incremental exercise; b) 15-min HRCLAMPED exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to that at 120% of GET determined in PRE; 3) two moderate-intensity constant WR (MOD) exercises. Breath-by-breath O2 uptake (V̇o2), HR, and other variables were determined. After BR, peak V̇o2 (V̇o2peak) and GET significantly decreased, by ∼10%. During HRCLAMPED (145 ± 11 beats·min-1), the decrease in WR needed to maintain a constant HR was greater in POST versus PRE (-39 ± 10% vs. -29 ± 14%, P < 0.01). In six subjects the decreased WR switched from the heavy- to the moderate-intensity domain. The decrease in WR during HRCLAMPED, in PRE versus POST, was significantly correlated with the V̇o2peak decrease (R2 = 0.52; P = 0.02). A greater amplitude of the slow component of the HR kinetics was observed during MOD following BR. Exercise at a fixed HR is not associated with a specific WR or WR domain; the problem, affecting exercise evaluation and prescription, is greater after BR. The WR decrease during HRCLAMPED is a biomarker of exercise intolerance after BR.NEW & NOTEWORTHY During a 15-min exercise carried out at a heart rate (HR) slightly above that corresponding to the gas exchange threshold, to keep HR constant work rate significantly decreased; the decrease was more pronounced after a 10-day horizontal bed rest. The work rate decrease at a fixed HR can be considered a systemic biomarker of exercise intolerance during microgravity/inactivity and could also be easily and reliably determined during spaceflights or in patients.

Peripheral impairments of oxidative metabolism after a 10-day bed rest are upstream of mitochondrial respiration.

In order to identify peripheral biomarkers of impaired oxidative metabolism during exercise following a 10-day bed rest, 10 males performed an incremental exercise (to determine peak pulmonary V̇O2 (V̇O2 p)) and moderate-intensity exercises, before (PRE) and after (POST) bed rest. Blood flow response was evaluated in the common femoral artery by Eco-Doppler during 1 min of passive leg movements (PLM). The intramuscular matching between O2 delivery and O2 utilization was evaluated by near-infrared spectroscopy (NIRS). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in isolated muscle fibres, and in vivo by NIRS by the evaluation of skeletal muscle V̇O2 (V̇O2 m) recovery kinetics. Resting V̇O2 m was estimated by NIRS. Peak V̇O2 p was lower in POST vs. PRE. The area under the blood flow vs. time curve during PLM was smaller (P = 0.03) in POST (274 ± 233 mL) vs. PRE (427 ± 291). An increased (P = 0.03) overshoot of muscle deoxygenation during a metabolic transition was identified in POST. Skeletal muscle citrate synthase activity was not different (P = 0.11) in POST (131 ± 16 nmol min-1  mg-1 ) vs. PRE (138 ± 19). Maximal ADP-stimulated mitochondrial respiration (66 ± 18 pmol s-1  mg-1 (POST) vs. 72 ± 14 (PRE), P = 0.41) was not affected by bed rest. Apparent Km for ADP sensitivity of mitochondrial respiration was reduced in POST vs. PRE (P = 0.04). The V̇O2 m recovery time constant was not different (P = 0.79) in POST (22 ± 6 s) vs. PRE (22 ± 6). Resting V̇O2 m was reduced by 25% in POST vs. PRE (P = 0.006). Microvascular-endothelial function was impaired following a 10-day bed rest, whereas mitochondrial mass and function (both in vivo and ex vivo) were unaffected or slightly enhanced. KEY POINTS: Ten days of horizontal bed rest impaired in vivo oxidative function during exercise. Microvascular impairments were identified by different methods. Mitochondrial mass and mitochondrial function (evaluated both in vivo and ex vivo) were unchanged or even improved (i.e. enhanced mitochondrial sensitivity to submaximal [ADP]). Resting muscle oxygen uptake was significantly lower following bed rest, suggesting that muscle catabolic processes induced by bed rest/inactivity are less energy-consuming than anabolic ones.

Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures.

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose-response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15-25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health.

Obese Patients Decrease Work Rate in Order to Keep a Constant Target Heart Rate.

PURPOSE: "Slow components" of heart rate (HR) kinetics, occurring also during moderate-intensity constant work rate exercise, represent a problem for exercise prescription at fixed HR values. This problem, described in young healthy subjects, could be more pronounced in obese patients. METHODS: Sixteen male obese patients (age, 22 ± 7 yr; body mass, 127 ± 19 kg; body mass index, 41.6 ± 3.9 kg·m-2) were tested before (PRE) and after (POST) a 3-wk multidisciplinary body mass reduction program, entailing moderate-intensity exercise. They performed on a cycle ergometer an incremental exercise to voluntary exhaustion (to determine peak pulmonary oxygen uptake (V˙O2peak) and gas exchange threshold (GET)) and constant work rate exercises: moderate-intensity (MODERATE; 80% of GET determined in PRE), heavy-intensity (HEAVY; 120% of GET determined in PRE), and "HRCLAMPED" exercise, in which work rate was continuously adjusted to maintain a constant HR corresponding to that at 120% of GET. Breath-by-breath V˙O2 and HR were determined. RESULTS: V˙O2peak and GET (expressed as a percent of V˙O2peak) were not significantly different in PRE versus POST. In POST versus PRE, the HR slow component disappeared (MODERATE) or was reduced (HEAVY). In PRE, work rate had to decrease by ~20% over a 15-min task in order to keep HR constant; this decrease was significantly smaller (~5%) in POST. CONCLUSIONS: In obese patients, a 3-wk multidisciplinary body mass reduction intervention i) increased exercise tolerance by eliminating (during MODERATE) or by reducing (during HEAVY) the slow component of HR kinetics, and ii) facilitated exercise prescription by allowing to translate a fixed submaximal HR value into a work rate slightly above GET.

Exercise training alone or in combination with high-protein diet in patients with late onset Pompe disease: results of a cross over study.

BACKGROUND: Late onset Pompe disease (LOPD) is a lysosomal neuromuscular disorder which can progressively impair the patients' exercise tolerance, motor and respiratory functions, and quality of life. The available enzyme replacement therapy (ERT) does not completely counteract disease progression. We investigated the effect of exercise training alone, or associated with a high-protein diet, on the exercise tolerance, muscle and pulmonary functions, and quality of life of LOPD patients on long term ERT. METHODS: The patients were asked to participate to a crossover randomized study comprehending a control period (free diet, no exercise) followed by 2 intervention periods: exercise or exercise + diet, each lasting 26 weeks and separated by 13 weeks washout periods. Exercise training included moderate-intensity aerobic exercise on a cycle ergometer, stretching and balance exercises, strength training. The diet was composed by 25-30% protein, 30-35% carbohydrate and 35-40% fat. Before and after each period patients were assessed for: exercise tolerance test on a cycle-ergometer, serum muscle enzymes, pulmonary function tests and SF36 questionnaire for quality of life. Compliance was evaluated by training and dietary diaries. Patients were contacted weekly by researchers to optimize adherence to treatments. RESULTS: Thirteen LOPD patients, median age 49 ± 11 years, under chronic ERT (median 6.0 ± 4.0 years) were recruited. Peak aerobic power (peak pulmonary O2 uptake) decreased after control, whereas it increased after exercise, and more markedlyafter exercise + diet. Serum levels of lactate dehydrogenase (LDH) significantly decreased after exercise + diet; both creatine kinase (CK) and LDH levels were significantly reduced after exercise + diet compared to exercise. Pulmonary function showed no changes after control and exercise, whereas a significant improvement of forced expiratory volume in 1 sec (FEV1) was observed after exercise + diet. SF36 showed a slight improvement in the "mental component" scale after exercise, and a significant improvement in "general health" and "vitality" after exercise + diet. The compliance to prescriptions was higher than 70% for both diet and exercise. CONCLUSIONS: Exercise tolerance (as evaluated by peak aerobic power) showed a tendency to decrease in LOPD patients on long term ERT. Exercise training, particularly if combined with high-protein diet, could reverse this decrease and result in an improvement, which was accompanied by improved quality of life. The association of the two lifestyle interventions resulted also in a reduction of muscle enzyme levels and improved pulmonary function.

Skeletal muscle V̇o2 kinetics by the NIRS repeated occlusions method during the recovery from cycle ergometer exercise.

Near-infrared spectroscopy (NIRS) has been utilized as a noninvasive method to evaluate skeletal muscle mitochondrial function in humans, by calculating muscle V̇o2 (V̇o2m) recovery (off-) kinetics following short light-intensity plantar flexion exercise. The aim of the present study was to determine V̇o2m off- kinetics following standard cycle ergometer exercise of different intensities. Fifteen young physically active healthy men performed an incremental exercise (INCR) up to exhaustion and two repetitions of constant work-rate (CWR) exercises at 80% of gas exchange threshold (GET; MODERATE) and at 40% of the difference between GET and peak pulmonary V̇o2 (V̇o2p; HEAVY). V̇o2p and vastus lateralis muscle fractional O2 extraction by NIRS (Δ[deoxy(Hb+Mb)]) were recorded continuously. Transient arterial occlusions were carried out at rest and during the recovery for V̇o2m calculation. All subjects tolerated the repeated occlusions protocol without problems. The quality of the monoexponential fitting for V̇o2m off-kinetics analysis was excellent (0.93≤r2≤0.99). According to interclass correlation coefficient, the test-retest reliability was moderate to good. V̇o2m values at the onset of recovery were ~27, ~38, and ~35 times higher (in MODERATE, HEAVY, and INCR, respectively) than at rest. The time constants (τ) of V̇o2m off-kinetics were lower (P < 0.001) following MODERATE (29.1 ± 6.8 s) vs. HEAVY (40.8 ± 10.9) or INCR (42.9 ± 10.9), suggesting an exercise intensity dependency of V̇o2m off-kinetics. Only following MODERATE the V̇o2m off-kinetics were faster than the V̇o2p off-kinetics. V̇o2m off-kinetics, determined noninvasively by the NIRS repeated occlusions technique, can be utilized as a functional evaluation tool of skeletal muscle oxidative metabolism also following conventional cycle ergometer exercise.NEW & NOTEWORTHY This is the first study in which muscle V̇o2 recovery kinetics, determined noninvasively by near-infrared spectroscopy (NIRS) by utilizing the repeated occlusions method, was applied following standard cycle ergometer exercise of different intensities. The results demonstrate that muscle V̇o2 recovery kinetics, determined noninvasively by the NIRS repeated occlusions technique, can be utilized as a functional evaluation tool of skeletal muscle oxidative metabolism also following conventional cycle ergometer exercise, overcoming significant limitations associated with the traditionally proposed protocol.

Human Physiology During Exposure to the Cave Environment: A Systematic Review With Implications for Aerospace Medicine.

Background: Successful long-duration missions outside low-Earth orbit will depend on technical and physiological challenges under abnormal environmental conditions. Caves, characterized by absence of light, confinement, three-dimensional human movement and long-duration isolation, are identifiably one of the earliest examples of scientific enquiry into space analogs. However, little is known about the holistic human physiological response during cave exploration or prolonged habitation. Objectives: The aim of our review was to conduct a systematic bibliographic research review of the effects of short and prolonged exposure to a cave environment on human physiology, with a view to extend the results to implications for human planetary exploration missions. Methods: A systematic search was conducted following the structured PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for electronic databases. Results: The search retrieved 1,519 studies. There were 50 articles selected for further consideration, of which 31 met our inclusion criteria. Short-term cave exposure studies have investigated visual dysfunction, cardiovascular, endocrine-metabolic, immunologic-hematological and muscular responses in humans. Augmentations of heart rate, muscular damage, initial anticipatory stress reaction and inflammatory responses were reported during caving activity. Prolonged exposure studies mainly investigated whether biological rhythms persist or desist in the absence of standard environmental conditions. Changes were evident in estimated vs. actual rest-activity cycle periods and external desynchronization, body temperature, performance reaction time and heart rate cycles. All studies have shown a marked methodological heterogeneity and lack reproduction under controlled conditions. Conclusions: This review facilitates a further comparison of the proposed physiological impact of a subterranean space analog environment, with existing knowledge in related disciplines pertaining to human operative preparation under challenging environmental conditions. This comprehensive overview should stimulate more reproducible research on this topic and offer the opportunity to advance study design and focus future human research in the cave environment on noteworthy, reproducible projects.

Expedition Cognition: A Review and Prospective of Subterranean Neuroscience With Spaceflight Applications.

Renewed interest in human space exploration has highlighted the gaps in knowledge needed for successful long-duration missions outside low-Earth orbit. Although the technical challenges of such missions are being systematically overcome, many of the unknowns in predicting mission success depend on human behavior and performance, knowledge of which must be either obtained through space research or extrapolated from human experience on Earth. Particularly in human neuroscience, laboratory-based research efforts are not closely connected to real environments such as human space exploration. As caves share several of the physical and psychological challenges of spaceflight, underground expeditions have recently been developed as a spaceflight analog for astronaut training purposes, suggesting that they might also be suitable for studying aspects of behavior and cognition that cannot be fully examined under laboratory conditions. Our objective is to foster a bi-directional exchange between cognitive neuroscientists and expedition experts by (1) describing the cave environment as a worthy space analog for human research, (2) reviewing work conducted on human neuroscience and cognition within caves, (3) exploring the range of topics for which the unique environment may prove valuable as well as obstacles and limitations, (4) outlining technologies and methods appropriate for cave use, and (5) suggesting how researchers might establish contact with potential expedition collaborators. We believe that cave expeditions, as well as other sorts of expeditions, offer unique possibilities for cognitive neuroscience that will complement laboratory work and help to improve human performance and safety in operational environments, both on Earth and in space.

Comparison between Slow Components of HR and V˙O2 Kinetics: Functional Significance.

PURPOSE: Aerobic exercise prescription is often based on a linear relationship between pulmonary oxygen consumption (V˙O2) and heart rate (HR). The aim of the present study was to test the hypothesis that during constant work rate (CWR) exercises at different intensities, the slow component of HR kinetics occurs at lower work rate and is more pronounced that the slow component of V˙O2 kinetics. METHODS: Seventeen male (age, 27 ± 4 yr) subjects performed on a cycle ergometer an incremental exercise to voluntary exhaustion and several CWR exercises: 1) moderate CWR exercises, below gas exchange threshold (GET); 2) heavy CWR exercise, at 45% of the difference between GET and V˙O2 peak (Δ); 3) severe CWR exercise, at 95% of Δ; 4) "HRCLAMPED" exercise in which work rate was continuously adjusted to maintain a constant HR, slightly higher than that determined at GET. Breath-by-breath V˙O2, HR, and other variables were determined. RESULTS: In moderate CWR exercises, no slow component of V˙O2 kinetics was observed, whereas a slow component with a relative amplitude (with respect to the total response) of 24.8 ± 11.0% was observed for HR kinetics. During heavy CWR exercise, the relative amplitude of the HR slow component was more pronounced than that for V˙O2 (31.6 ± 11.2% and 23.3 ± 9.0%, respectively). During HRCLAMPED, the decrease in work rate (~14%) needed to maintain a constant HR was associated with a decreased V˙O2 (~10%). CONCLUSIONS: The HR slow component occurred at a lower work rate and was more pronounced than the V˙O2 slow component. Exercise prescriptions at specific HR values, when carried out for periods longer than a few minutes, could lead to premature fatigue.