Physiological determinants of mechanical efficiency during advanced ageing and disuse.

This study aimed to determine which physiological factors impact net efficiency (ηnet) in oldest-old individuals at different stages of skeletal muscle disuse. To this aim, we examined ηnet, central haemodynamics, peripheral circulation, and peripheral factors (skeletal muscle fibre type, capillarization and concentration of mitochondrial DNA [mtDNA]). Twelve young (YG; 25 ± 2 years), 12 oldest-old mobile (OM; 87 ± 3 years), and 12 oldest-old immobile (OI; 88 ± 4 years) subjects performed dynamic knee extensor (KE) and elbow flexors (EF) exercise. Pulmonary oxygen uptake, photoplethysmography, Doppler ultrasound and muscle biopsies of the vastus lateralis and biceps brachii were used to assess central and peripheral adaptations to advanced ageing and disuse. Compared to the YG (12.1 ± 2.4%), the ηnet of lower-limb muscle was higher in the OM (17.6 ± 3.5%, P < 0.001), and lower in the OI (8.9 ± 1.9%, P < 0.001). These changes in ηnet during KE were coupled with significant peripheral adaptations, revealing strong correlations between ηnet and the proportion of type I muscle fibres (r = 0.82), as well as [mtDNA] (r = 0.77). No differences in ηnet were evident in the upper-limb muscles between YG, OM and OI. In view of the differences in limb-specific activity across the lifespan, these findings suggest that ηnet is reduced by skeletal muscle inactivity and not by chronological age, per se. Likewise, this study revealed that the age-related changes in ηnet are not a consequence of central or peripheral haemodynamic adaptations, but are likely a product of peripheral changes related to skeletal muscle fibre type and mitochondrial density. KEY POINTS: Although the effects of ageing and muscle disuse deeply impact the cardiovascular and skeletal muscle function, the combination of these factors on the mechanical efficiency are still a matter of debate. By measuring both upper- and lower-limb muscle function, which experience differing levels of disuse, we examined the influence of central and peripheral haemodynamics, and skeletal muscle factors linked to mechanical efficiency. Across the ages and degree of disuse, upper-limb muscles exhibited a preserved work economy. In the legs the oldest-old without mobility limitations exhibited an augmented mechanical efficiency, which was reduced in those with an impairment in ambulation. These changes in mechanical efficiency were associated with the proportion of type I muscle fibres. Recognition that the mechanical efficiency is not simply age-dependent, but the consequence of inactivity and subsequent skeletal muscle changes, highlights the importance of maintaining physical activity across the lifespan.

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.

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Central and peripheral haemodynamics at exercise onset: the role of central command.

PURPOSE: The involvement of central command in central hemodynamic regulation during exercise is relatively well-known, although its contribution to peripheral hemodynamics at the onset of low-intensity contractions is debated. This study sought to examine central and peripheral hemodynamics during electrically-evoked muscle contractions (without central command) and voluntary muscle activity (with central command). METHODS: Cyclic quadriceps isometric contractions (1 every second), either electrically-evoked (ES; 200 ms trains composed of 20 square waves) or performed voluntarily (VC), were executed by 10 healthy males (26 ± 3 years). In both trials, matched for force output, peripheral and central hemodynamics were analysed. RESULTS: At exercise onset, both ES and VC exhibited equal peaks of femoral blood flow (1276 ± 849 vs. 1117 ± 632 ml/min, p > 0.05) and vascular conductance (15 ± 11 vs. 13 ± 7 ml/min/mmHg, p > 0.05), respectively. Similar peaks of heart rate (86 ± 16 bpm vs. 85 ± 16 bpm), stroke volume (100 ± 20 vs. 99 ± 27 ml), cardiac output (8.2 ± 2.5 vs. 8.5 ± 2.1 L/min), and mean arterial pressure (113 ± 13 vs. 113 ± 3 mmHg), were recorded (all, p > 0.05). After ~ 50 s, all the variables drifted to lower values. Collectively, the hemodynamics showed equal responses. CONCLUSION: These results suggest a similar pathway for the initial (first 40 s) increase in central and peripheral hemodynamics. The parallel responses may suggest an initial minimal central command involvement during the onset of low-intensity contractions, likely associated with a neural drive activation delay or threshold.

Stroke volume response during prolonged exercise depends on left ventricular filling: evidence from a ß-blockade study.

Prolonged moderate-intensity exercise leads to a progressive upward drift in heart rate (HR) that may compromise stroke volume (SV). Alternatively, the HR drift may be related to abated SV due to impaired ventricular function. The aim of this study was to examine the effects of cardiovascular drift on left ventricular volumes and in turn SV. Thirteen healthy young males completed two 60-min cycling bouts on a semirecumbent cycle ergometer at 57% maximal oxygen consumption (V̇o2max) either under placebo condition (CON) or after ingesting a small dose of ß1-blockers (BB). Measurements of HR, end-diastolic volume (EDV), and end-systolic volume were obtained by echocardiography and used to calculate SV. Other variables such as ear temperature, skin temperature, blood pressure, and blood volume were measured to assess potential changes in thermoregulatory needs and loading conditions. HR drift was successfully prevented when using BB from min 10 to min 60 (128 ± 9 to 126 ± 8 beats/min, P = 0.29) but not in CON (134 ± 10 to 148 ± 10 beats/min, P < 0.01). Conversely, during the same time, SV increased by 13% when using BB (103 ± 9 to 116 ± 7 mL, P < 0.01), whereas it was unchanged in CON (99 ± 7 to 101 ± 9 mL, P = 0.37). The SV behavior was mediated by a 4% increase in EDV in the BB condition (164 ± 18 to 170 ± 18 mL, P < 0.01), whereas no change was observed in the CON condition (162 ± 18 to 160 ± 18 mL, P = 0.23). In conclusion, blocking HR drift enhances EDV and SV during prolonged exercise. These findings suggest that SV behavior is tightly related to filling time and loading conditions of the left ventricle.

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 exercise induced muscle damage on cardiovascular responses to isometric muscle contractions and post-exercise circulatory occlusion.

PURPOSE: The aim of the present study was to investigate whether exercise-induced muscle damage (EIMD) influences cardiovascular responses to isometric exercise and post-exercise circulatory occlusion (PECO). We hypothesized that EIMD would increase muscle afferent sensitivity and, accordingly, increase blood pressure responses to exercise and PECO. METHODS: Eleven male and nine female participants performed unilateral isometric knee extension at 30% of maximal voluntary contraction (MVC) for 3-min. A thigh cuff was rapidly inflated to 250 mmHg for two min PECO, followed by 3 min recovery. Heart rate and blood pressure were monitored beat-by-beat, with stroke volume and cardiac output estimated from the Modelflow algorithm. Measurements were taken before and 48 h after completing eccentric knee-extension contractions to induce muscle damage (EIMD). RESULTS: EIMD caused 21% decrease in MVC (baseline: 634.6 ± 229.3 N, 48 h: 504.0 ± 160 N), and a 17-fold increase in perceived soreness using a visual-analogue scale (0-100 mm; VASSQ) (both p < 0.001). CV responses to exercise and PECO were not different between pre and post EIMD. However, mean arterial pressure (MAP) was higher during the recovery phase after EIMD (p < 0.05). Significant associations were found between increases in MAP during exercise and VASSQ, Rate of Perceived Exertion (RPE) and Pain after EIMD only (all p < 0.05). CONCLUSION: The MAP correlations with muscle soreness, RPE and Pain during contractions of damaged muscles suggests that higher afferent activity was associated with higher MAP responses to exercise.

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.

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.

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.

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.

Fasting-Mimicking-Diet does not reduce skeletal muscle function in healthy young adults: a randomized control trial.

PURPOSE: The aim of this study was to evaluate the short- and long-term effects of the Fasting-Mimicking-Diet (FMD) intervention on neuromuscular parameters of force production in healthy young men. METHODS: Twenty-four physically active men completed the study. Participants were randomly assigned to Fasting-Mimicking (FMD) or Normal Diet (ND) and asked to follow three cycles of dietary intervention. Neuromuscular parameters of force production during maximal voluntary isometric contractions (MVCs) with the leg extensors muscles and anthropometrics were measured at baseline (T0), at the end of the first cycle (T1), and 7-10 days after the 3rd cycle of the nutritional intervention (T2). The study was registered on Clinicaltrials.gov (No. NCT04476615). RESULTS: There was a significant decrease in body mass at T1 for FMD (- 2.6 kg, ∆ from baseline, on average; p < 0.05) but not in ND (- 0.1 kg;). Neuromuscular parameters of force production, muscle volume, and MVC torque did not change or differ between groups across visits. Results were similar even when parameters were normalized by muscle volume. CONCLUSION: The consumption of FMD in a group of young healthy male subjects showed to be feasible, and it did not affect neuromuscular parameters of force production. The results suggest that FMD could be safely adopted by strength athletes without detrimental effects on force and muscle volume. Further research in clinical population at risk of muscle mass loss, such as elderly and obese subjects with sarcopenia, is warranted.

Relationship between perceived and neuromuscular fatigue in COPD patients with chronic respiratory failure with long-term oxygen therapy: a cross-sectional study.

PURPOSE: To evaluate perceived fatigue (PF) and neuromuscular fatigue (NMF) in patients with COPD and chronic respiratory failure (CRF) on long-term oxygen therapy (CRF-COPD group), and the relationships between PF, NMF, patient's characteristics, comparing severe patients with COPD to patients without CRF (COPD group). METHODS: This cross-sectional study compared 19 CRF-COPD patients with 10 COPD patients attending a rehabilitation program. PF was determined by Fatigue Severity Scale (FSS), while dyspnea by the Barthel Dyspnea Index (BDI). We assessed quadriceps NMF via electrical nerve stimulation during and following a Maximal Voluntary Contraction (MVC) detecting changes after a Constant Workload Cycling Test (CWCT) at 80% of the peak power output at exhaustion. RESULTS: CRF-COPD patients showed higher PF (+ 1.79 of FSS score, p = 0.0052) and dyspnea (+ 21.03 of BDI score, p = 0.0023) than COPD patients. After the fatiguing task and normalization for the total work, there was a similar decrease in the MVC (CRF-COPD -1.5 ± 2.4 vs COPD -1.1 ± 1.2% baseline kJ-1, p = 0.5819), in the potentiated resting twitch force (CRF-COPD -2.8 ± 4.7 vs COPD -2.0 ± 3.3% baseline kJ-1, p = 0.7481) and in the maximal voluntary activation (CRF-COPD -0.1 ± 3.9 vs COPD -0.9 ± 1.2 -2.0 ± 3.3% baseline kJ-1, p = 0.4354). FSS and BDI were closely related (R = 0.5735, p = 0.0011), while no correlation between PF and NMF was found. CONCLUSION: Patients with CRF-COPD develop higher levels of perceived fatigue and dyspnea than patients with COPD; while neuromuscular fatigue is similar, suggesting a mismatch between symptoms and neuromuscular dysfunction.

Including the Eccentric Phase in Resistance Training to Counteract the Effects of Detraining in Women: A Randomized Controlled Trial.

ABSTRACT: Coratella, G, Beato, M, Bertinato, L, Milanese, C, Venturelli, M, and Schena, F. Including the eccentric phase in resistance training to counteract the effects of detraining in women: a randomized controlled trial. J Strength Cond Res 36(11): 3023-3031, 2022-The current study compared the effects of concentric-based (CONC), eccentric-based (ECC), and traditional concentric-eccentric (TRAD) resistance training on muscle strength, mass, and architecture and the postdetraining retention of the training-induced effects in women. Sixty women were randomly assigned to unilateral volume-equated CONC, ECC, or TRAD knee extension training or control ( N = 15 per group). Before training, after an 8-week intervention period, and after an 8-week detraining period, isokinetic concentric, eccentric, and isometric torque were measured. In addition, thigh lean mass was assessed by dual X-ray absorptiometry and vastus lateralis thickness, pennation angle, and fascicle length by ultrasound. After training, concentric and isometric torque increased ( p < 0.05) similarly in all groups, whereas eccentric torque increased more in ECC than that in CONC (+13.1%, effect size (ES): 0.71 [0.04-1.38]) and TRAD (+12.6%, ES: 0.60 [0.12-1.08]). Thigh lean mass increased in ECC (+6.1%, ES: 0.47 [0.27-0.67]) and TRAD (+3.1%, ES: 0.33 [0.01-0.65]). Vastus lateralis thickness and pennation angle increased ( p < 0.05) similarly in all groups, whereas fascicle elongation was visible in ECC (+9.7%, ES: 0.92 [0.14-1.65]) and TRAD (+7.1%, ES: 0.64 [0.03-1.25]). After detraining, all groups retained ( p < 0.05) similar concentric torque. ECC and TRAD preserved eccentric torque ( p < 0.05), but ECC more than TRAD (+17.9%, ES: 0.61 [0.21-1.21]). All groups preserved isometric torque ( p < 0.05), but ECC more than CONC (+14.2%, ES: 0.71 [0.04-1.38]) and TRAD (+13.8%, ES: 0.65 [0.10-1.20]). Thigh lean mass and vastus lateralis fascicle length were retained only in ECC ( p < 0.05), pennation angle was preserved in all groups ( p < 0.05), and thickness was retained in CONC and ECC ( p < 0.05). Including the eccentric phase in resistance training is essential to preserve adaptations after detraining.

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.

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.

Exercise training improves vascular function in patients with Alzheimer's disease.

PURPOSE: Vascular dysfunction has been demonstrated in patients with Alzheimer's disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. METHODS: Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate-high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. RESULTS: EX group has increased FMD% (+ 3.725%, p < 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p < 0.05; SR + 134%, p < 0.05), but not during CTRL treatment. CONCLUSION: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population.

Bone and skeletal muscle changes in oldest-old women: the role of physical inactivity.

BACKGROUND: Alterations in bone and muscle parameters related to advanced aging and physical inactivity have never been investigated in oldest-old women. AIMS: To investigate the impact of physical inactivity on bone mineral density (BMD) and body composition at the systemic and regional levels in oldest-old (> 75 years old) women. We hypothesized that, further to aging, alterations in bone and body composition parameters are exacerbated in the locomotor limbs that have experienced physical inactivity. METHODS: Whole-body and regional (lower limbs and trunk) BMD and fat-free soft tissue mass (FFSTM) were measured by means of dual-energy X-ray absorptiometry in 11 oldest-old wheelchair-bound women (OIW), 11 oldest-old mobile women (OMW), and 11 young healthy women (YW), all matched for weight (± 10 kg), height (± 10 cm). RESULTS: Whole-body BMD was reduced by 15% from YW to OMW and 10% from OMW to OIW. Whole-body FFSTM was also reduced from YW to OIW (- 13%). Lower limb BMD was progressively reduced among YW, OMW and OIW (- 23%). Similarly, lower limb FFSTM was reduced among YW (12,816 ± 1797 g), OMW (11,999 ± 1512 g) and OIW (10,037 ± 1489 g). Trunk BMD was progressively reduced among YW, OMW and OIW (- 19%), while FFSTM was similar among the three groups ~ 19801 g. CONCLUSIONS: The results of the present study suggest that the alterations in bone and body composition parameters are exacerbated in the physical inactive oldest-old. These negative effects of physical inactivity are not confined to the locomotor limbs, and a systemic decline of bone and muscle parameters are likely associated with the physical inactivity.

Regulation of microRNAs in Satellite Cell Renewal, Muscle Function, Sarcopenia and the Role of Exercise.

Sarcopenia refers to a condition of progressive loss of skeletal muscle mass and function associated with a higher risk of falls and fractures in older adults. Musculoskeletal aging leads to reduced muscle mass and strength, affecting the quality of life in elderly people. In recent years, several studies contributed to improve the knowledge of the pathophysiological alterations that lead to skeletal muscle dysfunction; however, the molecular mechanisms underlying sarcopenia are still not fully understood. Muscle development and homeostasis require a fine gene expression modulation by mechanisms in which microRNAs (miRNAs) play a crucial role. miRNAs modulate key steps of skeletal myogenesis including satellite cells renewal, skeletal muscle plasticity, and regeneration. Here, we provide an overview of the general aspects of muscle regeneration and miRNAs role in skeletal mass homeostasis and plasticity with a special interest in their expression in sarcopenia and skeletal muscle adaptation to exercise in the elderly.

Skeletal Muscle Function in the Oldest-Old: The Role of Intrinsic and Extrinsic Factors.

Although skeletal muscle function is diminished with advanced age, single muscle fiber function seems to be preserved. Therefore, this review examines the hypothesis that the skeletal muscle fiber, per se, is not the predominant factor responsible for the reduction in force-generating capacity in the oldest-old, but, rather, is attributable to a combination of factors external to the muscle fibers.