Skeletal muscle fiber type and TMS-induced muscle relaxation in unfatigued and fatigued knee-extensor muscles.

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

Limb, sex, but not acute dietary capsaicin, modulate the near-infrared spectroscopy-vascular occlusion test estimate of muscle metabolism.

The downward slope during the near-infrared spectroscopy (NIRS)-vascular occlusion test (NIRS-VOT) is purported as a simplified estimate of metabolism. Whether or not the NIRS-VOT exhibits sex- or limb-specificity or may be acutely altered remains to be elucidated. Thus, we investigated if there is limb- or sex specificity in tissue desaturation rates (DeO2) during a NIRS-VOT, and if acute dietary capsaicin may alter this estimate of muscle metabolism. Young healthy men (n = 25, 21 ± 4 years) and women (n = 20, 20 ± 1 years) ingested either placebo or capsaicin, in a counterbalanced, single-blind, crossover design after which a simplified NIRS-VOT was conducted to determine the DeO2 (%/s), as an estimate of oxidative muscle metabolism, in both the forearm (flexors) and thigh (vastus lateralis). There was a significant limb effect with the quadriceps having a greater DeO2 than the forearm (-2.31 ± 1.34 vs. -1.78 ± 1.22%/s, p = 0.007, ηp 2 = 0.19). There was a significant effect of sex on DeO2 (p = 0.005, ηp 2 = 0.203) with men exhibiting a lesser DeO2 than women (-1.73 ± 1.03 vs. -2.36 ± 1.32%/s, respectively). This manifested in significant interactions of limb*capsaicin (p = 0.001, ηp 2 = 0.26) as well as limb*capsaicin*sex on DeO2 (p = 0.013, ηp 2 = 0.16) being observed. Capsaicin does not clearly alter O2-dependent muscle metabolism, but there was apparent limb and sex specificity, interacting with capsaicin in this NIRS-derived assessment.

Sex differences in neuromuscular and biological determinants of isometric maximal force.

AIM: Force expression is characterized by an interplay of biological and molecular determinants that are expected to differentiate males and females in terms of maximal performance. These include muscle characteristics (muscle size, fiber type, contractility), neuromuscular regulation (central and peripheral factors of force expression), and individual genetic factors (miRNAs and gene/protein expression). This research aims to comprehensively assess these physiological variables and their role as determinants of maximal force difference between sexes. METHODS: Experimental evaluations include neuromuscular components of isometric contraction, intrinsic muscle characteristics (proteins and fiber type), and some biomarkers associated with muscle function (circulating miRNAs and gut microbiome) in 12 young and healthy males and 12 females. RESULTS: Male strength superiority appears to stem primarily from muscle size while muscle fiber-type distribution plays a crucial role in contractile properties. Moderate-to-strong pooled correlations between these muscle parameters were established with specific circulating miRNAs, as well as muscle and plasma proteins. CONCLUSION: Muscle size is crucial in explaining the differences in maximal voluntary isometric force generation between males and females with similar fiber type distribution. Potential physiological mechanisms are seen from associations between maximal force, skeletal muscle contractile properties, and biological markers.

Concurrent metaboreflex activation increases chronotropic and ventilatory responses to passive leg movement without sex-related differences.

Previous studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5 min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation ([Formula: see text]) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4 bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7 L min-1, p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs - 3 ± 3 mmHg, p < 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p < 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15 ms, p = 0.04). No difference was found in all the other measured variables between conditions (p > 0.05). These findings suggest that mechanoreflex-mediated increases in HR and [Formula: see text] are sensitized by metabolites accumulation. These responses were not influenced by biological sex.

Sex differences in estimates of cardiac autonomic function using heart rate variability: effects of dietary capsaicin.

PURPOSE: Heart rate variability (HRV) estimates the autonomic nervous system (ANS) influence on the heart and appears sex-specific. Sensory afferents exhibit sex-specificity; although, it is unknown if Capsaicin, an agonist for transient receptor potential vanilloid channel-1 (TRPV1), alters cardiac ANS activity in a sex-dependent manner, which could be important given the predictive nature of HRV on risk of developing hypertension. Thus, we explored if there was sex-specificity in the effect of capsaicin on estimated cardiac ANS activity. METHODS: HRV was measured in 38 young males (M: n = 25) and females (F: n = 13), in a blinded-crossover design, after acute ingestion of placebo or capsaicin. Resting HR, RR-interval, root-mean-square of successive differences (RMSSD), natural log-transformed RMSSD (LnRMSSD), standard deviation of n-n intervals (SDNN), number of pairs of successive n-n intervals differing by > 50 ms (NN50), and percent NN50 (PNN50) were obtained using standard techniques. RESULTS: Significant sex differences were observed in mean HR (M: 59 ± 9.3 vs. F: 65 ± 12 beats/min, p = 0.036, η2 = 0.098), minimum HR (M: 47 ± 8.3 vs. F: 56 ± 12 beats/min, p = 0.014, η2 = 0.124), and NN50 (M: 177 ± 143 vs. F: 29 ± 17, p < 0.001, η2 = 0.249). There was a significant interaction of sex*treatment (p = 0.02, η2 = 0.027) for RMSSD, where males increased (78 ± 55 vs. 91 ± 64 ms), and females decreased (105 ± 83 vs. 76 ± 43 ms), placebo vs. capsaicin. CONCLUSION: This controlled study recapitulates sex differences in HR and HRV, but revealed a sexual dimorphism in the parasympathetic response to capsaicin, perhaps due to differing TRPV1-afferent sensitivity, highlighting a potential mechanism for differential regulation of hemodynamics, and CVD risk, and should be considered in future studies.

The role of muscle mass in vascular remodeling: insights from a single-leg amputee model.

PURPOSE: Both muscle mass and physical activity are independent mechanisms that play a role in vascular remodeling, however, the direct impact of muscle mass on the structure and function of the vessels is not clear. The aim of the study was to determine the impact of muscle mass alteration on lower limbs arterial diameter, blood flow, shear rate and arterial stiffness. METHODS: Nine (33 ± 13 yrs) male individuals with a single-leg amputation were recruited. Vascular size (femoral artery diameter), hemodynamics (femoral artery blood flow and shear rate were measured at the level of the common femoral artery in both amputated (AL) and whole limbs (WL). Muscle mass of both limbs, including thigh for AL and thigh and leg for WL, was measured with a DXA system. RESULTS: AL muscle mass was reduced compared to the WL (3.2 ± 1.2 kg vs. 9.4 ± 2.1 kg; p = 0.001). Diameter of the femoral artery was reduced in the AL (0.5 ± 0.1 cm) in comparison to the WL (0.9 ± 0.2 cm, p = 0.001). However, femoral artery blood flow normalized for the muscle mass (AL = 81.5 ± 78.7ml min-1 kg-1,WL = 32.4 ± 18.3; p = 0.11), and blood shear rate (AL = 709.9 ± 371.4 s-1, WL = 526,9 ± 295,6; p = 0.374) were non different between limbs. A correlation was found only between muscle mass and femoral artery diameter (p = 0.003, R = 0.6561). CONCLUSION: The results of this study revealed that the massive muscle mass reduction caused by a leg amputation, but independent from the level of physical activity, is coupled by a dramatic arterial diameter decrease. Interestingly, hemodynamics and arterial stiffness do not seem to be impacted by these structural changes.

Does sex influence near-infrared spectroscopy-derived indicators of microvascular reactivity and the response to acute dietary capsaicin.

Endothelial dysfunction is associated with cardiovascular disease development, nitric oxide (NO) deficiencies, and may be limb or sex-specific. Prior in vitro work indicated that the transient receptor potential vanilloid channel-1 (TRPV1) is expressed in human arteries and the TRPV1 agonist capsaicin alters vasodilation in an endothelium-dependent manner; however, it is unknown if this translates in vivo or is limb or sex-dependent. Therefore, we sought to determine if there was limb or sex-specificity in the effect of capsaicin on microvascular function using near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (StO2) reperfusion slope. In a blinded placebo-controlled crossover design, 45 young males (M: n = 25) and females (F: n = 20), the reperfusion slopes of the forearm and quadriceps were assessed, and a urine sample obtained to assay for nitrate/nitrite (NOx) concentrations and antioxidant capacity after acutely ingesting placebo or capsaicin. Under placebo, females had greater reperfusion rates in both the forearm (M: 0.44 ± 0.24 vs. F: 0.98 ± 0.46 %/sec; p = 0.002, d = -1.50) and quadricep (M: 0.86 ± 0.31 vs. F: 1.17 ± 0.43 %/sec; p = 0.010, d = -0.85). Capsaicin decreased microvascular responsiveness in the forearm of females (placebo: 0.98 ± 0.45 vs. capsaicin: 0.84 ± 0.45 %/sec) as compared to males (placebo: 0.45 ± 0.24 vs. capsaicin: 0.38 ± 0.16 %/sec, interaction p < 0.001, η2 = 0.475). There was a sex*treatment interaction for NOx concentrations, where males increased (placebo: 21.13 ± 12.83 vs. capsaicin: 23.82 ± 13.34 µM), while females decreased (placebo: 22.78 ± 14.40 vs. capsaicin: 14.43 ± 10.01 µM; p = 0.037, η2 = 0.042). Using NIRS to assess microvascular function, there is apparent limb and sex-specificity, and, for the first-time, document that acute oral capsaicin alters reperfusion slope in a sexually divergent manner.

Effects of nociceptive and mechanosensitive afferents sensitization on central and peripheral hemodynamics following exercise-induced muscle damage.

This study aims to test the separated and combined effects of mechanoreflex activation and nociception through exercise-induced muscle damage (EIMD) on central and peripheral hemodynamics before and during single passive leg movement (sPLM). Eight healthy young males undertook four experimental sessions, in which a sPLM was performed on the dominant limb while in each specific session the contralateral was: 1) in a resting condition (CTRL), 2) stretched (ST), 3) resting after EIMD called delayed onset muscle soreness (DOMS) condition, or 4) stretched after EIMD (DOMS + ST). EIMD was used to induce DOMS in the following 24-48 h. Femoral blood flow (FBF) was assessed using Doppler ultrasound whereas central hemodynamics were assessed via finger photoplethysmography. Leg vascular conductance (LVC) was calculated as FBF/mean arterial pressure (MAP). RR-intervals were analyzed in the time (root mean squared of successive intervals; RMSSD) and frequency domain [low frequency (LF)/high frequency (HF)]. Blood samples were collected before each condition and gene expression analysis showed increased fold changes for P2X4 and IL1ß in DOMS and DOMS + ST compared with baseline. Resting FBF and LVC were decreased only in the DOMS + ST condition (-26 mL/min and -50 mL/mmHg/min respectively) with decreased RMSSD and increased LF/HF ratio. MAP, HR, CO, and SV were increased in ST and DOMS + ST compared with CTRL. Marked decreases of Δpeaks and AUC were observed for FBF (Δ: -146 mL/min and -265 mL respectively) and LVC (Δ: -8.66 mL/mmHg/min and ±1.7 mL/mmHg/min respectively) all P < 0.05. These results suggest that the combination of mechanoreflex and nociception resulted in decreased vagal tone and concomitant rise in sympathetic drive that led to increases in resting central hemodynamics with reduced limb blood flow before and during sPLM.NEW & NOTEWORTHY Exercise-induced muscle damage (EIMD) is a well-known model to study mechanical hyperalgesia and muscle peripheral nerve sensitizations. The combination of static stretching protocol on the damaged limb extensively increases resting central hemodynamics with reduction in resting limb blood flow and passive leg movement-induced hyperemia. The mechanism underlining these results may be linked to reduction of vagal tone with concomitant increase in sympathetic activity following mechano- and nociceptive activation.

Strategies targeting the NO pathway to counteract extra-pulmonary manifestations of COPD: A systematic review and meta-analysis.

The clinical symptoms of chronic obstructive pulmonary disease (COPD) disease are accompanied by severely debilitating extra-pulmonary manifestations, including vascular dysfunction and hypertension. This systematic review evaluated the current evidence for several therapeutic interventions, targeting the nitric oxide (NO) pathway on hemodynamics and, secondarily, exercise capacity in patients with COPD. A comprehensive search on COPD and NO donors was performed on online databases. Of 934 initially found manuscripts, 27 were included in the review, and 16 in the meta-analysis. The analysis indicated inconsistent effects of dietary nitrate supplementation on exercise tolerance in COPD patients. Dietary nitrate supplementation decreased systolic (-3.7 ± 4.3 mmHg; p = 0.10) and diastolic blood pressure (BP; -2.6 ± 3.2 mmHg; p = 0.05) compared with placebo. When restricted to acute studies, a clinically relevant BP lowering effect of nitrate supplementation during diastole was observed (-4.7 ± 3.2 mmHg; n = 5; p = 0.05). In contrast, inhaled NO (iNO) at doses <20 ppm (+9.2 ± 11.3 mmHg) and 25-40 ppm (-5±2 mmHg) resulted in inconsistent effects on PaO2 (p = 0.48). Data on the effect of iNO on exercise capacity were too limited and inconsistent, but preliminary evidence suggests a possible benefit of iNO on pulmonary vascular resistance during exercise in severe COPD patients. Overall, the effects of acute dietary nitrate supplementation on BP may be of clinical relevance as an adjunct therapy and deserve further investigation in large sample size studies of COPD patients with and without cardiovascular comorbidities. iNO exerted inconsistent physiological effects, with the use of high doses posing safety risks.

Brain Structural and Functional Alterations in Multiple Sclerosis-Related Fatigue: A Systematic Review.

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS); it influences patients' quality of life. The etiology of fatigue is complex, and its pathogenesis is still unclear and debated. The objective of this review was to describe potential brain structural and functional dysfunctions underlying fatigue symptoms in patients with MS. To reach this purpose, a systematic review was conducted of published studies comparing functional brain activation and structural brain in MS patients with and without fatigue. Electronic databases were searched until 24 February 2021. The structural and functional outcomes were extracted from eligible studies and tabulated. Fifty studies were included: 32 reported structural brain differences between patients with and without fatigue; 14 studies described functional alterations in patients with fatigue compared to patients without it; and four studies showed structural and functional brain alterations in patients. The results revealed structural and functional abnormalities that could correlate to the symptom of fatigue in patients with MS. Several studies reported the differences between patients with fatigue and patients without fatigue in terms of conventional magnetic resonance imaging (MRI) outcomes and brain atrophy, specifically in the thalamus. Functional studies showed abnormal activation in the thalamus and in some regions of the sensorimotor network in patients with fatigue compared to patients without it. Patients with fatigue present more structural and functional alterations compared to patients without fatigue. Specifically, abnormal activation and atrophy of the thalamus and some regions of the sensorimotor network seem linked to fatigue.

Reliability of relaxation properties of knee-extensor muscles induced by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS)-induced relaxation rate reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. To determine the appropriateness of knee-extensor muscle relaxation measurements induced by TMS, this study aimed to establish both the within- and between-session reliability before and after a fatiguing exercise bout. Eighteen participants (9 females, 9 males, age 25 ± 2 years, height 171 ± 9 cm, body mass 68.5 ± 13.5 kg) volunteered to participate in two identical sessions approximately 30 days apart. Maximal and submaximal neuromuscular evaluations were performed with TMS six times before (PRE) and at the end (POST) of a 2-min sustained maximal voluntary isometric contraction. Within- and between-session reliability of PRE values were assessed with intraclass correlation coefficient (ICC2,1, relative reliability), repeatability coefficient (absolute reliability), and coefficient of variation (variability). Test-retest reliability of post-exercise muscle relaxation rates was assessed with Bland-Altman plots. For both the absolute and normalized peak relaxation rates and time to peak relaxation, data demonstrated low variability (e.g. coefficient of variation ≤ 7.8%) and high reliability (e.g. ICC2,1 ≥ 0.963). Bland-Altman plots showed low systematic errors. These findings establish the reliability of TMS-induced muscle relaxation rates in unfatigued and fatigued knee-extensor muscles, showing that TMS is a useful technique that researchers can use when investigating changes in muscle relaxation rates both in unfatigued and fatigued knee-extensor muscles.

Prior Involvement of Central Motor Drive Does Not Impact Performance and Neuromuscular Fatigue in a Subsequent Endurance Task.

PURPOSE: This study evaluated whether central motor drive during fatiguing exercise plays a role in determining performance and the development of neuromuscular fatigue during a subsequent endurance task. METHODS: On separate days, 10 males completed three constant-load (80% peak power output), single-leg knee-extension trials to task failure in a randomized fashion. One trial was performed without preexisting quadriceps fatigue (CON), and two trials were performed with preexisting quadriceps fatigue induced either by voluntary (VOL; involving central motor drive) or electrically evoked (EVO; without central motor drive) quadriceps contractions (~20% maximal voluntary contraction (MVC)). Neuromuscular fatigue was assessed via pre-post changes in MVC, voluntary activation (VA), and quadriceps potentiated twitch force ( Qtw,pot ). Cardiorespiratory responses and rating of perceived exertion were also collected throughout the sessions. The two prefatiguing protocols were matched for peripheral fatigue and stopped when Qtw,pot declined by ~35%. RESULTS: Time to exhaustion was shorter in EVO (4.3 ± 1.3 min) and VOL (4.7 ± 1.5 min) compared with CON (10.8 ± 3.6 min, P < 0.01) with no difference between EVO and VOL. ΔMVC (EVO: -47% ± 8%, VOL: -45% ± 8%, CON: -53% ± 8%), Δ Qtw,pot (EVO: -65% ± 7%, VOL: -59% ± 14%, CON: -64% ± 9%), and ΔVA (EVO: -9% ± 7%, VOL: -8% ± 5%, CON: -7% ± 5%) at the end of the dynamic task were not different between conditions (all P > 0.05). Compared with EVO (10.6 ± 1.7) and CON (6.8 ± 0.8), rating of perceived exertion was higher ( P = 0.05) at the beginning of VOL (12.2 ± 1.0). CONCLUSIONS: These results suggest that central motor drive involvement during prior exercise plays a negligible role on the subsequent endurance performance. Therefore, our findings indicate that peripheral fatigue-mediated impairments are the primary determinants of high-intensity single-leg endurance performance.

Does Parkinson's disease affect peripheral circulation and vascular function in physically active patients?

Previous studies demonstrated that aging, neurodegeneration, and the level of physical activity are associated with vascular alterations. However, in Parkinson's disease (PD) only cerebral vascular function has been investigated; instead, the contribution of PD on systemic vascular function and skeletal muscle circulation remains a matter of debate. In this study, the hyperemic response during the single passive leg movement test (sPLM), largely nitric oxide dependent, was examined at the level of the common femoral artery with an ultrasound Doppler system to assess systemic vascular function in 10 subjects with PD (PDG), compared with 10 aged-sex and physically active matched healthy elderly (EHG), and 10 physically active young healthy individuals (YHG). Interestingly, femoral blood flow at rest, normalized for the thigh volume, was similar in PDG (64 ± 15 mL·min-1·L-1), EHG (44 ± 8 mL·min-1·L-1), and YHG (58 ± 11 mL·min-1·L-1, all P values > 0.05). The sPLM-induced hyperemic response appeared markedly lower in PDG and EHG compared with YHG (8.3 ± 0.1 vs. 9.8 ± 0.8 vs. 17.3 ± 3.0 mL·min-1·L-1; P < 0.05) but the difference between PDG and EHG was negligible (P > 0.05). The results of our study indicate that peripheral circulation and vascular function are not reduced in physically active patients with PD, suggesting that these vascular changes could resemble the physiological adjustments of aging, without any impact from the disease.NOTE & NOTEWORTHY Our study verified an intact peripheral circulation in patients with Parkinson's disease (PD). However, using the single passive leg movement, we observed a similar reduction of the vascular integrity in physically active patients and matched elderly, compared with young, likely induced by aging but independent on the pathology. This comparable effect confirmed that the disease, at early stage, with a dynamic lifestyle does not worsen the vascular system but reveals the cardinal symptoms of PD.

Capsaicin and Its Effect on Exercise Performance, Fatigue and Inflammation after Exercise.

Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: -52 ± 6 vs. CAP: -42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: -47 ± 33 vs. CAP: -29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.

Evidence that Neuromuscular Fatigue Is not a Dogma in Patients with Parkinson's Disease.

PURPOSE: Given the increased level of fatigue frequently reported by patients with Parkinson's disease (PD), this study investigated the interaction between central and peripheral components of neuromuscular fatigue (NF) in this population compared with healthy peers. METHODS: Changes in maximal voluntary activation (ΔVA, central fatigue) and potentiated twitch force (ΔQtw,pot, peripheral fatigue) pre-post exercise were determined via the interpolated twitch technique in 10 patients with PD and 10 healthy controls (CTRL) matched for age, sex, and physical activity. Pulmonary gas exchange, femoral blood flow, and quadriceps EMG were measured during a fatiguing exercise (85% of peak power output [PPO]). For a specific comparison, on another day, CTRL repeat the fatiguing test matching the time to failure (TTF) and PPO of PD. RESULTS: At 85% of PPO (PD, 21 ± 7 W; CTRL, 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, femoral blood flow, and EMG. After this exercise, the maximal voluntary contraction (MVC) force and Qtwpot decreased equally in both groups (-16%, P = 0.483; -43%, P = 0.932), whereas VA decreased in PD compared with CTRL (-3.8% vs -1.1%, P = 0.040). At the same PPO and TTF of PD (21 W; 5.4 min), CTRL showed a constant drop in MVC, and Qtwpot (-14%, P = 0.854; -39%, P = 0.540), instead VA decreased more in PD than in CTRL (-3.8% vs -0.7%, P = 0.028). CONCLUSIONS: In PD, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRL, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations.

Electrically induced quadriceps fatigue in the contralateral leg impairs ipsilateral knee extensors performance.

Muscle fatigue induced by voluntary exercise, which requires central motor drive, causes central fatigue that impairs endurance performance of a different, nonfatigued muscle. This study investigated the impact of quadriceps fatigue induced by electrically induced (no central motor drive) contractions on single-leg knee-extension (KE) performance of the subsequently exercising ipsilateral quadriceps. On two separate occasions, eight males completed constant-load (85% of maximal power-output) KE exercise to exhaustion. In a counterbalanced manner, subjects performed the KE exercise with no pre-existing quadriceps fatigue in the contralateral leg on one day (No-PreF), whereas on the other day, the same KE exercise was repeated following electrically induced quadriceps fatigue in the contralateral leg (PreF). Quadriceps fatigue was assessed by evaluating pre- to postexercise changes in potentiated twitch force (ΔQtw,pot; peripheral fatigue), and voluntary muscle activation (ΔVA; central fatigue). As reflected by the 57 ± 11% reduction in electrically evoked pulse force, the electrically induced fatigue protocol caused significant knee-extensors fatigue. KE endurance time to exhaustion was shorter during PreF compared with No-PreF (4.6 ± 1.2 vs 7.7 ± 2.4 min; P < 0.01). Although ΔQtw,pot was significantly larger in No-PreF compared with PreF (-60% vs -52%, P < 0.05), ΔVA was greater in PreF (-14% vs -10%, P < 0.05). Taken together, electrically induced quadriceps fatigue in the contralateral leg limits KE endurance performance and the development of peripheral fatigue in the ipsilateral leg. These findings support the hypothesis that the crossover effect of central fatigue is mainly mediated by group III/IV muscle afferent feedback and suggest that impairments associated with central motor drive may only play a minor role in this phenomenon.

The key role of physical activity against the neuromuscular deterioration in patients with Parkinson's disease.

AIM: Decreased muscle strength has been frequently observed in individuals with Parkinson's disease (PD). However, this condition is still poorly examined in physically active patients. This study compared quadriceps (Q) maximal force and the contribution of central and peripheral components of force production during a maximal isometric task between physically active PD and healthy individuals. In addition, the correlation between force determinants and energy expenditure indices were investigated. METHODS: Maximal voluntary contraction (MVC), resting twitch (RT) force, pennation angle (θp), physiological cross-sectional area (PCSA) and Q volume were assessed in 10 physically active PD and 10 healthy control (CTRL) individuals matched for age, sex and daily energy expenditure (DEE) profile. RESULTS: No significant differences were observed between PD and CTRL in MVC (142 ± 85; 142 ± 47 N m), Q volume (1469 ± 379; 1466 ± 522 cm3 ), PCSA (206 ± 54; 205 ± 71 cm2 ), θp (14 ± 7; 13 ± 3 rad) and voluntary muscle-specific torque (MVC/PCSA [67 ± 35; 66 ± 19 N m cm-2 ]). Daily calories and MVC correlated (r = 0.56, P = .0099). However, PD displayed lower maximal voluntary activation (MVA) (85 ± 7; 95 ± 5%), rate of torque development (RTD) in the 0-0.05 (110 ± 70; 447 ± 461 N m s-1 ) and the 0.05-0.1 s (156 ± 135; 437 ± 371 N m s-1 ) epochs of MVCs, whereas RT normalized for PCSA was higher (35 ± 14; 20 ± 6 N m cm-2 ). CONCLUSION: Physically active PDs show a preserved strength of the lower limb. This resulted by increasing skeletal muscle contractility, which counterbalances neuromuscular deterioration, likely due to their moderate level of physical activity.

Guidelines on exercise testing and prescription for patients at different stages of Parkinson's disease.

BACKGROUND: Exercise is highly recommended in patients with Parkinson's disease (PD). Exercise-induced amelioration of motor, non-motor, and drug-induced symptoms are widely known. However, specific guidelines on exercise testing and prescription in PD are lacking. OBJECTIVE: This study reviews the literature on exercise-based approaches to the management of symptoms at each stage of the disease and evaluate: (1) the most suitable clinical exercise testing; (2) training programs based on testing outcomes and PD stage; (3) the effects of exercise on antiparkinsonian drugs and to suggest the most effective exercise-medication combination. METHODS: A systematic search was conducted using the databases MEDLINE, Google Scholar and, Cochrane Library using "Parkinson's Disease AND Physical therapy", "Training AND Parkinson", "Exercise", "Exercise AND Drug" as key words. In addition, references list from the included articles were searched and cross-checked to identify any further potentially eligible studies. RESULTS: Of a total of 115 records retrieved, 50 (43%) were included. From these, 23 were included under the rubric "exercise testing"; 20 focused on the effectiveness of different types of exercise in PD motor-functional symptoms and neuroprotective effects, throughout disease progression, were included under the rubric "training protocol prescription"; and 7 concern the rubric "interaction between exercise and medication", although none reported consistent results. CONCLUSIONS: Despite the lack of standardized parameters for exercise testing and prescription, all studies agree that PD patients should be encouraged to regularly train according to their severity-related limitations and their personalized treatment plan. In this manuscript, specific guidelines for tailored clinical testing and prescription are provided for each stage of PD.