Supraspinal Fatigue Impedes Recovery From a Low-Intensity Sustained Contraction in Old Adults

This study determined the contribution of supraspinal fatigue and contractile properties to the age difference in neuromuscular fatigue during and recovery from a low-intensity sustained contraction. Cortical stimulation was used to evoke measures of voluntary activation and muscle relaxation during and after a contraction sustained at 20% of maximal voluntary contraction (MVC) until task failure with elbow flexor muscles in 14 young adults (20.9 ± 3.6 yr, 7 men) and 14 old adults (71.6 ± 5.4 yr, 7 men). Old adults exhibited a longer time to task failure than the young adults (23.8 ± 9.0 vs. 11.5 ± 3.9 min, respectively, P \u3c 0.001). The time to failure was associated with initial peak rates of relaxation of muscle fibers and pressor response (P \u3c 0.05). Increments in torque (superimposed twitch; SIT) generated by transcranial magnetic stimulation (TMS) during brief MVCs, increased during the fatiguing contraction (P \u3c 0.001) and then decreased during recovery (P = 0.02). The increase in the SIT was greater for the old adults than the young adults during the fatiguing contraction and recovery (P \u3c 0.05). Recovery of MVC torque was less for old than young adults at 10 min post-fatiguing contraction (75.1 ± 8.7 vs. 83.6 ± 7.8% of control MVC, respectively, P = 0.01) and was associated with the recovery of the SIT (r = −0.59, r2 = 0.35, P \u3c 0.001). Motor evoked potential (MEP) amplitude and the silent period elicited during the fatiguing contraction increased less for old adults than young adults (P \u3c 0.05). The greater fatigue resistance with age during a low-intensity sustained contraction was attributable to mechanisms located within the muscle. Recovery of maximal strength after the low-intensity fatiguing contraction however, was impeded more for old adults than young because of greater supraspinal fatigue. Recovery of strength could be an important variable to consider in exercise prescription of old populations

Supraspinal Fatigue Is Similar in Men and Women for a Low-Force Fatiguing Contraction

Purpose: This study determined the contribution of supraspinal fatigue to the sex difference in neuromuscular fatigue for a low-intensity fatiguing contraction. Because women have greater motor responses to arousal than men, we also examined whether cortical and motor nerve stimulation, techniques used to quantify central fatigue, would alter the sex difference in muscle fatigue. Methods: In study 1, cortical stimulation was elicited during maximal voluntary contractions (MVC) before and after a submaximal isometric contraction at 20% MVC with the elbow flexor muscles in 29 young adults (20 ± 2.6 yr, 14 men). In study 2, 10 men and 10 women (19.1 ± 2.9 yr) performed a fatiguing contraction in the presence and absence of cortical and motor nerve stimulation. Results: Study 1: Men had a briefer time to task failure than women (P = 0.009). Voluntary activation was reduced after the fatiguing contraction (P \u3c 0.001) similarly for men and women. Motor-evoked potential area and the EMG silent period increased similarly with fatigue for both sexes. Peak relaxation rates, however, were greater for men than women and were associated with time to task failure (P \u3c 0.05). Force fluctuations, RPE, HR, and mean arterial pressure increased at a greater rate for men than for women during the fatiguing contraction (P \u3c 0.05). Study 2: Time to task failure, force fluctuations, and all other physiological variables assessed were similar for the control session and stimulation session (P\u3e 0.05) for both men and women. Conclusions: Supraspinal fatigue was similar for men and women after the low-force fatiguing contraction, and the sex difference in muscle fatigue was associated with peripheral mechanisms. Furthermore, supraspinal fatigue can be quantified in both men and women without influencing motor performance

Stressor-Induced Increase in Muscle Fatigability of Young Men and Women is Predicted by Strength but Not Voluntary Activation

This study investigated mechanisms for the stressor-induced changes in muscle fatigability in men and women. Participants performed an isometric-fatiguing contraction at 20% maximal voluntary contraction (MVC) until failure with the elbow flexor muscles. Study one (n = 55; 29 women) involved two experimental sessions: 1) a high-stressor session that required a difficult mental-math task before and during a fatiguing contraction and 2) a control session with no mental math. For some participants (n = 28; 14 women), cortical stimulation was used to examine mechanisms that contributed to muscle fatigability during the high-stressor and control sessions. Study two (n = 23; nine women) determined the influence of a low stressor, i.e., a simple mental-math task, on muscle fatigability. In study one, the time-to-task failure was less for the high-stressor session than control (P \u3c 0.05) for women (19.4%) and men (9.5%): the sex difference response disappeared when covaried for initial strength (MVC). MVC force, voluntary activation, and peak-twitch amplitude decreased similarly for the control and high-stressor sessions (P \u3c 0.05). In study two, the time-to-task failure of men or women was not influenced by the low stressor (P \u3e 0.05). The greater fatigability, when exposed to a high stressor during a low-force task, was not exclusive to women but involved a strength-related mechanism in both weaker men and women that accelerated declines in voluntary activation and slowing of contractile properties

Stressor-Induced Increase in Muscle Fatigability of Young Men and Women is Predicted by Strength but Not Voluntary Activation

This study investigated mechanisms for the stressor-induced changes in muscle fatigability in men and women. Participants performed an isometric-fatiguing contraction at 20% maximal voluntary contraction (MVC) until failure with the elbow flexor muscles. Study one (n = 55; 29 women) involved two experimental sessions: 1) a high-stressor session that required a difficult mental-math task before and during a fatiguing contraction and 2) a control session with no mental math. For some participants (n = 28; 14 women), cortical stimulation was used to examine mechanisms that contributed to muscle fatigability during the high-stressor and control sessions. Study two (n = 23; nine women) determined the influence of a low stressor, i.e., a simple mental-math task, on muscle fatigability. In study one, the time-to-task failure was less for the high-stressor session than control (P \u3c 0.05) for women (19.4%) and men (9.5%): the sex difference response disappeared when covaried for initial strength (MVC). MVC force, voluntary activation, and peak-twitch amplitude decreased similarly for the control and high-stressor sessions (P \u3c 0.05). In study two, the time-to-task failure of men or women was not influenced by the low stressor (P \u3e 0.05). The greater fatigability, when exposed to a high stressor during a low-force task, was not exclusive to women but involved a strength-related mechanism in both weaker men and women that accelerated declines in voluntary activation and slowing of contractile properties

Skeletal Muscle Fatigability in Heart Failure

Evidence suggests that heart failure (HF) patients experience skeletal muscle fatigability in the lower extremity during single-limb tasks. The contribution of skeletal muscle fatigability to symptoms of exercise intolerance (perceived fatigue and dyspnea) is relatively unclear. Symptomatic or ‘perceived’ fatigue is defined by the sensations of exhaustion or tiredness that patients experience either at rest or while performing a motor task. Although factors that contribute to symptoms of fatigue in patients with HF are multifactorial; the skeletal muscle likely plays a major role. Skeletal muscle fatigability, as opposed to symptomatic fatigue, is an objective measure of a reduction in muscle force or power or reduced ability of the muscles to perform over time. Indeed, evidence suggests that patients with HF experience greater skeletal muscle fatigability which may contribute to a diminution in motor performance and the overall symptomatology that is hallmark of exercise intolerance in HF. This review will discuss (1) skeletal muscle fatigability in patients with HF, (2) the mechanisms contributing to locomotor skeletal muscle fatigability in HF and (3) the relationship of fatigability to symptoms of perceived fatigue and exercise intolerance in HF patients. Evidence suggests that cardiac dysfunction alone does not contribute to exercise intolerance. Therefore, mechanisms of skeletal muscle fatigability and their contribution to symptoms of fatigue and exercise intolerance, is an increasingly important consideration as we develop rehabilitative strategies for improving motor performance and functional capacity in patients with HF

Baroreflex sensitivity in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg ± SD) and 17 sex- and age-matched controls (age: 47 ± 14 years, p \u3e 0.05). People with FSHD were less active (Activity Metabolic Index, AMI) (FSHD: 24 ± 30; controls: 222 ± 175 kcal/day; p \u3c 0.001) but had a similar body mass index compared with controls (FSHD: 27 ± 4; controls: 27 ± 4 kg/m2 ; p \u3e 0.05). BRSup (hypertensive response), BRSdown (hypotensive response), and total BRS were similar between groups (BRSup: FSHD: 12 ± 8; controls: 12 ± 5 ms/mmHg; BRSdown: FSHD: 10 ± 4; controls: 13 ± 6 ms/mmHg; BRS: FSHD: 14 ± 9; controls: 13 ± 6 ms/mmHg; p \u3e 0.05). Mean arterial pressure was similar between groups (FSHD: 96 ± 7; controls: 91 ± 6mmHg). Individuals with FSHD had an elevated heart rate compared with controls (FSHD: 65 ± 8; controls: 59 ± 8 BPM; p = 0.03), but when co-varied for AMI, this relationship disappeared (p = 0.39). These findings suggest that BRS is not attenuated in people with FSHD, but an elevated heart rate may be due to low physical activity levels, a potential consequence of limited mobility

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals.

AIM: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. RESULTS: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p  0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). CONCLUSION: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged

S-nitrosylation of NADPH oxidase regulates cell death in plant immunity

Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol- mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe