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

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

On the role of group III/IV muscle afferent feedback on endurance performance, neuromuscular fatigue, and autonomic adjustments to exercise

Afferent feedback mechanisms and reflex arcs represent fundamental regulatory systems for several processes such as motor control, proprioception, and autonomic adjustments to physiological stressors. Nowadays, compelling evidence exists that feedback mediated by group III/IV thin afferent fibers plays a quintessential role in contributing to maintain an appropriate locomotor muscle O2 delivery by facilitating cardiovascular and ventilatory responses to exercise and eventually delaying the onset of fatigue. Concurrently however, this feedback also inhibits neural drive to the muscle and facilitate central fatigue, which results in a negative effect on performance. Because of the ambivalent and “contradictory” nature of this feedback, the net effect on exercise performance and neuromuscular fatigue is still somewhat unclear. Throughout the years, many advancements have been done in this field through the discovery and optimization of the methods and tools apt to separate the influence of the different regulatory systems that contribute to the neurocirculatory adjustments to exercise. However, the redundancy existing in the regulation of physiological systems, make this endeavor challenging. In this dissertation, particular effort was put into separating the effects of group III/IV afferent feedback, from the potential effects played by the voluntary descending drive. Therefore, the purpose of this dissertation was to elucidate the role of group III/IV afferent feedback on exercise performance, neuromuscular fatigue, and autonomic adjustments to exercise in young healthy individuals. In Chapter 1, a brief introduction about the history of group III/IV afferent feedback is provided. In Chapter 2, a detailed literature review was performed in order to give a comprehensive background on the role of group III/IV afferent feedback on the autonomic adjustments to exercise, the neuromuscular fatigue processes, and exercise performance. In Chapter 3 the aims of the study are highlighted. Successively, Chapters 4, 5, and 6 include the results of the original investigations on this topic. Finally, Chapter 7 provides a summary and an ensemble view of our findings, highlighting strengths and weaknesses of our research, and providing future directions for further studies

Stroke volume response during prolonged exercise depends on left ventricular filling: Evidence from a beta-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-minute cycling bouts on a semi-recumbent cycle ergometer at 57%VO2max either under placebo condition (CON) or after ingesting a small dose of β1-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 min10 to min60 (128±9 to 126±8bpm, p=0.29) but not in CON (134±10 to 148±10bpm, p<0.01). Conversely, during the same time, SV increased by 13% when using BB (103±9 to 116±7mL, p<0.01) while it was unchanged in CON (99±7 to 101±9mL, p=0.37). The SV behavior was mediated by a 4% increase in EDV in the BB condition (164±18 to 170±18mL, p<0.01), while no change was observed in the CON condition (162±18 to 160±18mL, 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

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

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 > 0.05). The sPLM-induced hyperemic response appeared markedly lower in PDG and EHG compared to 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

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 to 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 (FBF), and quadriceps electromyography (EMG) were measured during a fatiguing exercise (85% of peak power output (PPO)). For a specific comparison, on another day, CTRLs repeat the fatiguing test matching the time to failure (TTF) and PPO of PDs. Results: At 85% of PPO (PD = 21 ± 7 W; CTRL = 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, FBF, and EMG. After this exercise, the maximal voluntary contraction force (MVC) and Qtwpot decreased equally in both groups (-16%, p = 0.483; -43%, p = 0.932), while VA decreased in PD compared to CTRL (-3.8% Vs -1.1%, p = 0.040). At the same PPO and TTF of PDs (21 W; 5.4 min), CTRLs 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). Conclusion: In PDs, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRLs, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations

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 haemodynamics 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: a) in a resting condition (CTRL), b) stretched (ST), c) resting after EIMD called delayed-onset-muscle-soreness (DOMS) condition, or d) stretched after EIMD (DOMS+ST). EIMD was used to induce DOMS in the following 24-48h. Femoral blood flow (FBF) was assessed using doppler ultrasound while central haemodynamics were assessed via finger photoplethysmography. Leg vascular conductance (LVC) was calculated as FBF/MAP. RR-interval were analyzed in the time (RMSSD) and frequency domain (LF/HF). Blood samples were collected before each condition and gene expression analysis showed increased fold changes for P2X4 and IL1β in DOMS and DOMS+ST compared with baseline. Resting FBF and LVC were decreased only in the DOMS+ST condition (-26ml/min and -50ml/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 delta peaks and AUC for FBF (∆: -146ml/min and -265ml respectively) and LVC (∆: -8.66ml/mmHg/min and ±1.7ml/mmHg/min respectively) all p<.05. These results suggest that combination of mechanoreflex and nociception resulted in decreased vagal tone and concomitant rise in sympathetic drive that led to increases in resting central hemodynamic with reduce limb blood flow before and during sPLM