Search

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, heightened chemosensory discharges of the carotid body (CB), which contributes to potentiate the ventilatory hypoxic response and elicits hypertension. We aimed to determine: 1) whether the persistence of cardiorespiratory alterations found in long-term CIH depend on the inputs from the CB and, 2) in what extension the activation of glial cells and neuroinflammation in the caudal region of the nucleus of the Solitary Tract (NTS) requires functional CB chemosensory activity. To evaluate these hypotheses, we exposed male mice to CIH for 60 days. At 50 days of CIH, CBs were denervated and animals were kept in CIH for 10 additional days. At the end of the experiments, we measured arterial blood pressure, breathing regularity, and hypoxic ventilatory response (HVR) and assessed astrocyte and microglia cell activation. Compared to Sham, CIH induces hypertension (MABP: 83.47±1.39 vs. 95.00±2.18 mmHg), disordered breathing (IS: 7.77±0.49 vs. 12.56±1.66), increased the HVR (1.69±0.17 vs. 4.31±0.87 ΔV E /min), and produced an early transient activation of astrocytes followed by a late and persistent activation of microglia in the NTS. In addition, CIH increased IL-1β, IL-6, and TNF-α levels in the NTS. Bilateral CB denervation after 50 days of CIH results in the restoration of normal glial cell activation in the NTS, lower levels of IL-6 and TNF-α, reductions in arterial blood pressure (83.47±1.38 mmHg) and HVR (1.63±0.43 ΔV E /min). Present results suggest that CB inputs to the NTS during long-term CIH contributes to maintain the cardiorespiratory alterations and the formation of a neuroinflammatory niche at the NTS by modifying glial cell activity.

Introduction: The aim of this study was to compare vastus lateralis (VL) and rectus femoris (RF) muscles for their nervous and mechanical adaptations during two bouts of downhill walking (DW) with load carriage performed 2 wk apart. Moreover, we investigated cardiometabolic and perceived exertion responses during both DW bouts., Methods: Seventeen participants performed two 45-min sessions of loaded DW (30% of body mass; slope, -25%; speed, 4.5 km·h -1 ) separated by 2 wk. Rating of perceived exertion, cost of walking, heart rate, and EMG activity of thigh muscles were assessed during the DW. Muscle shear elastic modulus ( μ ) of RF and VL were assessed before each exercise bout. Maximal voluntary contraction torque was assessed before (PRE), immediately after (POST), and 24 and 48 h after the two exercise bouts., Results: Maximal voluntary contraction torque decreased from POST (-23.7% ± 9.2%) to 48 h (-19.2% ± 11.9%) after the first exercise (Ex1), whereas it was significantly reduced only at POST (-14.6% ± 11.0%) after the second exercise (Ex2; P < 0.001). Rating of perceived exertion (Ex1: 12.3 ± 1.9; Ex2: 10.8 ± 2.0), heart rate (Ex1: 156 ± 23 bpm; Ex2: 145 ± 25 bpm), cost of walking (Ex1: 4.5 ± 0.9 J·m -1 ·kg -1 ; Ex2: 4.1 ± 0.7 J·m -1 ·kg -1 ), and RF EMG activity (Ex1: 0.071 ± 0.028 mV; Ex2: 0.041 ± 0.014 mV) were significantly decreased during Ex2 compared with Ex1 ( P < 0.01). RF μ was significantly greater in Ex2 (0.44 ± 0.18) compared with Ex1 (0.56 ± 0.27; P < 0.001)., Conclusions: The RF muscle displayed specific mechanical and nervous adaptations to repeated DW bouts as compared with VL. Moreover, the muscle adaptations conferred by the first bout of DW could have induced greater exercise efficiency, inducing lesser perceived exertion and cardiometabolic demand when the same exercise was repeated 2 wk later., (Copyright © 2023 by the American College of Sports Medicine.)

Aims: In mammals, central chemoreception plays a crucial role in the regulation of breathing function in both health and disease conditions. Recently, a correlation between high levels of superoxide anion (O 2 .- ) in the Retrotrapezoid nucleus (RTN), a main brain chemoreceptor area, and enhanced central chemoreception has been found in rodents. Interestingly, deficiency in superoxide dismutase 2 (SOD2) expression, a pivotal antioxidant enzyme, has been linked to the development/progression of several diseases. Despite, the contribution of SOD2 on O 2 .- regulation on central chemoreceptor function is unknown. Accordingly, we sought to determine the impact of partial deletion of SOD2 expression on i) O 2 .- accumulation in the RTN, ii) central ventilatory chemoreflex function, and iii) disordered-breathing. Finally, we study cellular localization of SOD2 in the RTN of healthy mice., Methods: Central chemoreflex drive and breathing function were assessed in freely moving heterozygous SOD2 knockout mice (SOD2 +/- mice) and age-matched control wild type (WT) mice by whole-body plethysmography. O 2 .- levels were determined in RTN brainstem sections and brain isolated mitochondria, while SOD2 protein expression and tissue localization were determined by immunoblot, RNAseq and immunofluorescent staining, respectively., Results: Our results showed that SOD2 +/- mice displayed reductions in SOD2 levels and high O 2 .- formation and mitochondrial dysfunction within the RTN compared to WT. Additionally, SOD2 +/- mice displayed a heightened ventilatory response to hypercapnia and exhibited overt signs of altered breathing patterns. Both, RNAseq analysis and immunofluorescence co-localization studies showed that SOD2 expression was confined to RTN astrocytes but not to RTN chemoreceptor neurons. Finally, we found that SOD2 +/- mice displayed alterations in RTN astrocyte morphology compared to RTN astrocytes from WT mice., Innovation & Conclusion: These findings provide first evidence of the role of SOD2 in the regulation of O 2 .- levels in the RTN and its potential contribution on the regulation of central chemoreflex function. Our results suggest that reductions in the expression of SOD2 in the brain may contribute to increase O 2 .- levels in the RTN being the outcome a chronic surge in central chemoreflex drive and the development/maintenance of altered breathing patterns. Overall, dysregulation of SOD2 and the resulting increase in O 2 .- levels in brainstem respiratory areas can disrupt normal respiratory control mechanisms and contribute to breathing dysfunction seen in certain disease conditions characterized by high oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The aim of the present study was to examine whether combining strength and endurance training would promote better improvements in neuromuscular characteristics and functional abilities than endurance training alone in obese adolescent girls enrolled in a weight-reduction program. Twenty-four obese adolescent girls (12-15 years) volunteered to participate in a 9-month training program. Participants were allocated into two groups following either (i) combined training (endurance + strength; E+ST) or (ii) endurance training (ET) program. Absolute and specific maximal torque, muscle size, and maximal voluntary activation level (VA) of the knee extensor (KE) and plantar flexor (PF) muscles were assessed. Moreover, functional abilities such as balance and fatigability during a maximal isometric intermittent contraction test of the KE muscles were measured before and after the intervention. The force of the adductor pollicis (AP) muscles was used as a control to account for any effect of growth or mechanical unloading on neuromuscular properties and muscle size. While absolute and specific torque of the KE (+14.7 ± 12.1% and +14.4 ± 15.5%; p < 0.05) and PF (+19.2 ± 16.7% and +18.3 ± 17.5%; p < 0.001) muscles increased in the E+ST group, PF torque decreased, and KE torque did not change in the ET group (-22.6 ± 10.5% and -15.0 ± 17.2%; p < 0.001). Moreover, the VA of the KE muscles increased for the E+ST (+6.1 ± 5.6%; p < 0.01) group and decreased for the ET group (-5.4 ± 5.4%; p < 0.05). In contrast, VA remained similar in the PF muscles for both groups. The number of repetitions during the fatigability test increased in the ET group (38.4 ± 22.3 vs. 84.1 ± 33.3; p = 0.032) and was unchanged in the E+ST group (50.8 ± 14.1 vs. 54.2 ± 37.8), but it was associated with a higher force level. Moreover, balance improved in the E+ST group, but not in the ET group. To conclude, physical training combining strength and endurance training promoted larger improvement in neuromuscular characteristics and functional abilities than endurance training alone in obese adolescent girls. Greater neuromuscular adaptations resulting from the E+ST training may be beneficial for preserving or even increasing functional abilities and possibly induce greater engagement in the active lifestyle of obese adolescents. However, the endurance component seems necessary in training programs to reduce fatigability during daily living activities., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. The aim of this study was to compare the physical performance, systemic inflammation, and oxidative stress of patients with moderate COPD, and to associate physical performance with inflammatory and oxidative stress plasma markers. Twenty CONTROL (n = 10) and moderate COPD (n = 10) patients participated in this study. Systematic inflammation and oxidative stress plasma markers, maximal aerobic capacity (VO 2peak ), and maximal isometric strength (MVIC) of the knee extensor (KE) muscles were measured. VO 2peak was 31.3% greater in CONTROL compared to COPD (P = 0.006). The MVIC strength of the KE was 43.9% greater in CONTROL compared to COPD (P = 0.002). Tumor necrosis factor-alpha (TNF-α) was 79.6% greater in COPD compared to CONTROL (P < 0.001). Glutathione peroxidase activity (GPx) activity was 27.5% lesser in COPD compared to CONTROL (P = 0.05). TNF-α concentration was correlated with KE MVC strength (R = -0.48; P = 0.045) and VO 2peak (R = -0.58; P = 0.01). Meanwhile, malondialdehyde (MDA) and GPx activity were not associated with KE strength or VO 2peak (P = 0.74 and P = 0.14, respectively). COPD patients showed lesser muscle strength and aerobic capacity than healthy control individuals. Furthermore, patients with COPD showed greater systemic inflammation and lesser antioxidant capacity than healthy counterparts. A moderate association was evident between levels of systemic inflammation and physical performance variables., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Young obese are generally stronger than their typically developing counterparts. Strength differences could be partly ascribed to nervous adaptations, due to the loading effect of carrying overweight. We hypothesized that central adaptations of the muscles highly involved in weight bearing, i.e., plantar flexors (PF) and knee extensors (KE) could be greater in girls than boys due to their reduced potential for muscle hypertrophy. Furthermore, it is possible that neuromuscular adaptations in weight-bearing muscles will be greater compared to the unloaded muscles such as the adductor pollicis (AP).Twenty-four non-obese and 21 obese (body mass index: 33 ± 4 kg·m -2 ) adolescent girls and boys (12-15 years) performed maximal voluntary isometric contractions (MVC) of the PF and KE muscles. Voluntary activation (VA), assessed with the twitch interpolation technique, the antagonist co-activation (Co-Act) level, and the normalized root-mean-square value (RMS) of the agonist muscles were measured to account for central adaptations.The results revealed a weight status effect (p < 0.001) on the absolute MVC torque and VA of both KE and PF muscles. Moreover, these differences were also related to the sex of the participants (p < 0.05) for the PF muscles. While the VA, absolute, and specific MVC torque were greater in obese compared with non-obese girls, no difference was found between boys. A similar Co-Act level was observed between groups, whatever the sex and muscle group considered. Finally, no significant differences were found for the AP regarding peripheral and neural factors.This study highlighted a favorable effect of obesity on the central mechanisms (i.e., VA) responsible for force production within the lower limb muscles. However, obesity-related central adaptation was only observed in girls for the PF muscles. Thus, the excess of body mass supported by the muscles involved in weight-bearing could act as a chronic training stimulus responsible for these adaptations in obese adolescents but mostly in girls., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Abstract: Valdes, O, Inzulza, S, Collao, N, Garcia-Vicencio, S, Tufano, JJ, Earp, J, Venegas, M, and Peñailillo, L. Eccentric cycling is an alternative to Nordic hamstring exercise to increase the neuromuscular function of knee flexors in untrained men. J Strength Cond Res 37(11): 2158-2166, 2023-Nordic hamstring exercise (NHE) has been proposed to reduce knee flexor (KF) injuries. However, submaximal alternatives to NHE are necessary for the clinical or weaker population. The aim of this study was to compare the effects of Nordic hamstring training (NHT) and eccentric cycling (ECC) training on the neuromuscular function of the KF. Twenty healthy men (27.7 ± 3.5 years) were randomly assigned into 2 groups that performed 10 training sessions (2-3 sessions·week-1) of either NHT (n = 10) or ECC (n = 10). Maximal voluntary isometric contraction of the KF and knee extensor (KE) muscles (MVICKF and MVICKE) was measured, and the hamstring/quadriceps strength (H/Q) ratio was calculated. Furthermore, changes in NHE maximum reaction force (NHE-MRFKF), NHE break-point angle (NHE-BPA), and muscle activity of the semitendinosus (STEMG) and biceps femoris (BFEMG) during the NHE after the interventions were compared. Although no group × time effects were observed (p = 0.09-0.70), but time effects were found for all variables. Pairwise comparisons revealed that MVICKF (+16.9%; p = 0.02), H/Q ratio (+11.8%; p = 0.01), NHE-MRFKF (+19.8%; p = 0.005), and NHE-BPA (+30.8%; p = 0.001) increased after ECC, whereas NHE-MRFKF (+9.7%; p = 0.003), NHE-BPA (+35.5%; p = 0.0002), and STEMG (+33.7%; p = 0.02) increased after NHT. A group × time effect was observed (p = 0.003) in BFEMG, revealing an increase only after ECC (+41.1%; p < 0.0001). Similar neuromuscular adaptations were found after both training modalities. Therefore, ECC provides similar adaptations as NHT and may serve as an alternative form of KF training for those unable to perform NHE., (Copyright © 2023 National Strength and Conditioning Association.)

Purpose: The aim of the present study was to investigate whether the electrically evoked muscle responses are differently affected over time by the knee joint angle after an exercise-induced muscle damage (EIMD). We hypothesized that low-frequency-evoked responses would be less affected at long than short muscle length, and that mechanisms located within the muscle and tendinous tissues would be involved., Methods: Fifteen males performed 45 min loaded downhill walking (DW) exercise. Maximal voluntary contraction torque (MVC), optimal angle for torque production, voluntary activation level (VAL), twitch, doublet at 10 and 100 Hz (Db10 and Db100, respectively), rate of torque development (RTD), post-activation potentiation (PAP), muscle shear elastic modulus (µ) and aponeurosis stiffness were assessed before, after, and 4, 24, 48, 72 and 168 h after the exercise at a knee angle of 40°, 90° and 120° (0°: full extension)., Results: MVC, VAL and Db100 were similarly decreased across joint angles after the DW and optimal angle was not affected. Twitch, Db10, Db10/Db100, PAP and RTD were less affected and muscle µ more increased at long than short muscle lengths (p < 0.05), especially during the first 24 h after the DW exercise., Conclusion: Low-frequency-evoked responses were more preserved at long than short muscle length the first 24 h after the DW exercise, suggesting that joint angle should be taken into account to assess muscular alterations after EIMD. This length-dependence could be associated to the higher sensitivity to Ca 2+ and the higher increase in muscle stiffness at long than short muscle length., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The neuromuscular system can quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). Circulating muscle-specific microRNAs (myomiRs) may be able to potentially predict the long-lasting maximal voluntary contraction (MVC) torque deficit (>24 h), an indicator of EIMD. We aimed to investigate: 1 ) how plasma myomiR levels are modified by the RBE and 2 ) whether plasma myomiRs can predict the long-lasting MVC torque deficit. Nineteen participants performed two identical bouts of loaded downhill walking separated by 2 wk. MVC torque, creatine kinase (CK) activity, myoglobin (Mb) concentration, and myomiR levels were measured before and up to 48 h after exercise. Correlation and multiple regression analyses were performed to assess the ability of these markers to predict the largest MVC torque loss beyond 24 h postexercise. Similar to MVC torque, CK activity, and the Mb concentration, the relative abundance of certain myomiRs (hsa-miR-1-3p, and hsa-miR-133a-3p) was less affected after the second bout of exercise relative to the first bout. The CK activity, Mb concentration, and level of several myomiRs (hsa-miR-1-3p, hsa-miR-133a-3p, and hsa-miR-206) correlated with long-lasting MVC torque loss. Multiple regression showed that the best combination of markers to predict the long-lasting deficit of MVC torque included several myomiRs, Mb, and CK. Certain myomiR levels increased less after exercise bout 2 than after exercise bout 1 , indicating the presence of the RBE. The measurement of myomiR levels in combination with Mb concentrations and CK activity could improve the prediction of the long-lasting MVC torque deficit. NEW & NOTEWORTHY The present study is the first to show that plasma muscle-specific microRNA (myomiR) levels can be modified by the repeated bout effect, as their levels increased less after the second exercise bout relative to the first. This study is also the first to suggest that myomiR levels could be used to partially predict maximal voluntary contraction torque loss at 24 h postexercise (i.e., the magnitude of exercise-induced muscle damage). Interestingly, the combined measurement of certain myomiR levels with those of myoglobin and creatine kinase improved the predictive value.

Purpose: The aim of this review was to (1) characterize the time-course of markers of exercise-induced muscle damage (EIMD) based on the level of maximal voluntary contraction torque loss at 24-48h post-exercise (MVCloss24-48h), (2) identify factors (e.g., exercise and population characteristics) affecting the level of MVCloss24-48h, and (3) evaluate the appropriateness of EIMD markers as indicators of MVCloss24-48h., Methods: Magnitude of change of each EIMD markers was normalized using the standardized mean differences method to compare the results from different studies. Time-course of EIMD markers were characterized according to three levels of MVCloss24-48h based on a clustering analysis of the 141 studies included. Association between MVCloss24-48h levels and participant´s characteristics or exercise type/modalities were assessed. Meta-regressions were performed to investigate the associations between MVCloss24-48h and EIMD markers changes at <6h, 24h, 48h, 72h and >96h after exercise., Results: Time-course of EIMD markers recovery differs between levels of MVCloss24-48h. Training status and exercise type/modality were associated with MVCloss24-48h level (p<0.05). MVCloss24-48h was correlated to changes in myoglobin concentration (<6h), jump height (24h) and range of motion (48h) (p<0.001)., Conclusion: As the exercise could differently affect markers as function of the EIMD severity (i.e., MVCloss24-48h levels), different markers should be used as function of the timing of measurement. Mb concentration should be used during the first hours after the exercise (<6h), whereas jump height (24h) and range of motion (48h) could be used as surrogate for maximal voluntary contraction later. Moreover, training status and exercise type/modality could influence the magnitude of MVCloss24-48h., Competing Interests: The authors have declared that no competing interests exist.

Background: The neuromuscular system is able to quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). The objective was to determine whether the mechanical properties of the quadriceps, as evaluated by shear wave elastography (SWE), were less affected when a second bout of eccentric-biased exercise was performed 2 weeks later. It was hypothesized that the first bout would confer protection against extensive muscle damage through an adaptation of the muscle stiffness before the second bout (i.e., higher muscle stiffness). Methods: Sixteen males performed two identical bouts of downhill walking separated by 2 weeks (45 min at 4.5 km.h -1 ; gradient: 25%; load: 30% of the body mass). Rectus femoris (RF) and vastus lateralis (VL) resting shear elastic modulus (µ) and EIMD symptoms were measured before and up to 7 days following the exercise bouts. Changes in neuromuscular function was evaluated by maximal voluntary contraction torque, voluntary activation level, evoked mechanical response to single and double (10 and 100 Hz doublets) electrical stimulation. An index of protection (IP) was calculated for EIMD symptoms to assess magnitude the RBE. Results: EIMD symptoms were less affected after the second than the first exercise bout. RF and VL-µ increased ( p < 0.001) only after the first exercise. RF µ was elevated up to 2 weeks after the end of the first exercise ( p < 0.001) whereas VL µ was only increased up to 24 h. The increase in µ observed 2 weeks after the end of the first exercise was correlated with the IP; i.e., attenuation of alterations in muscle µ, 10 Hz-doublet amplitude and rate of torque development after the second exercise bout ( p < 0.05). Conclusion: We showed that muscle µ assessed by SWE was sensitive to the RBE, with a differential effect between VL and RF. The persistent increase in µ was associated with the attenuation of neuromuscular impairments observed after the second bout, suggesting that the increased muscle stiffness could be a "protective" adaptation making muscles more resistant to the mechanical strain associated to eccentric contractions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chalchat, Siracusa, Bourrilhon, Charlot, Martin and Garcia-Vicencio.)

Introduction: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis., Methods: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis., Results: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04)., Conclusions: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases., (© 2022 S. Karger AG, Basel.)