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

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

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

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

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

On The Science Of Sex Differences: An In-Depth Study On Muscle Force And Neuromuscular Fatigue

This dissertation seeks to explore the biological and neurophysiological factors that contribute to sex differences in maximal force expression and neuromuscular fatigue development. While it is known that many aspects of human physiology differ between males and females, the extent to which these differences influence performance is not yet fully understood. Unfortunately, sex differences in human physiology are often understudied and overlooked in research and clinical practice, despite significant advances in our understanding of the human body. This dissertation seeks to fill this gap by examining the current state of knowledge on sex differences in human physiology (Background Chapter) and presenting new insights into the mechanisms underlying these differences (Study One and Study Two). In pursuit of this objective, the initial study of this thesis centered on elucidating the sexual dimorphism in maximal force production, with a focus on understanding the underlying physiological mechanisms. In doing so, the determinants of maximal force expression were studied from a neurophysiological standpoint, and their biological associations were investigated. Moreover, this first study can be considered as a comprehensive characterization of the biological sex differences observed within our cohort of participants. On the other hand, the second study focused on elucidating the differences in neuromuscular fatigue between males and females. With an emphasis on understanding the reasons for the lower neuromuscular fatigue development that has been consistently reported for females in the literature, the second study sought to unravel the mechanisms that may underlie these differences. Through a comprehensive analysis of various determinants of fatigue, from the central to the peripheral components, the study aimed to shed light on the potential factors contributing to the observed sex differences in neuromuscular fatigue development

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

Muscle cramps: A comparison of the two-leading hypothesis

Exercise-Associated Muscle Cramps (EAMC) are a common painful condition of muscle spasms. Despite scientists tried to understand the physiological mechanism that underlies these common phenomena, the etiology is still unclear. From 1900 to nowadays, the scientific world retracted several times the original hypothesis of heat cramps. However, recent literature seems to focus on two potential mechanisms: the dehydration or electrolyte depletion mechanism, and the neuromuscular mechanism. The aim of this review is to examine the recent literature, in terms of physiological mechanisms of EAMC. A comprehensive search was conducted on PubMed and Google Scholar. The following terminology was applied: muscle cramps, neuromuscular hypothesis (or thesis), dehydration hypothesis, Exercise-Associated muscle cramps, nocturnal cramps, muscle spasm, muscle fatigue. From the initial literature of 424 manuscripts, sixty-nine manuscripts were included, analyzed, compared and summarized. Literature analysis indicates that neuromuscular hypothesis may prevails over the initial hypothesis of the dehydration as the trigger event of muscle cramps. New evidence suggests that the action potentials during a muscle cramp are generated in the motoneuron soma, likely accompanied by an imbalance between the rising excitatory drive from the muscle spindles (Ia) and the decreasing inhibitory drive from the Golgi tendon organs. In conclusion, from the latest investigations there seem to be a spinal involvement rather than a peripheral excitation of the motoneurons