Prefrontal cortex activation during incremental inspiratory loading in healthy participants.

We aimed to investigate whether changes in prefrontal cortex (PFC) oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) associates with inspiratory muscle effort during inspiratory threshold loading (ITL) in healthy participants. Participants performed an incremental ITL. Breathing pattern, partial pressure of end-tidal CO2 (PETCO2), mouth pressure and O2Hb and HHb over the right dorsolateral PFC, sternocleidomastoid (SCM), and diaphragm/intercostals (Dia/IC) were monitored. Fourteen healthy participants (8 men; 29 ± 5 years) completed testing. Dyspnea was higher post- than pre-ITL (5 ± 1 vs. 0 ± 1, respectively; P<0.05). PFC O2Hb increased (P < 0.001) and HHb decreased (P = 0.001) at low loads but remained stable with increasing ITL intensities. PFC total hemoglobin increased at task failure compared to rest. SCM HHb increased throughout increasing intensities. SCM and Dia/IC total hemoglobin increased in the at task failure compared to rest. PETCO2 did not change (P = 0.528). PFC is activated early during the ITL but does not show central fatigue at task failure despite greater dyspnea and an imbalance of SCM oxygen demand and delivery.

Early Inflammation in Muscular Dystrophy Differs between Limb and Respiratory Muscles and Increases with Dystrophic Severity.

Duchenne muscular dystrophy (DMD) is a genetic, degenerative, striated muscle disease exacerbated by chronic inflammation. Mdx mice in the genotypic DMD model poorly represent immune-mediated pathology observed in patients. Improved understanding of innate immunity in dystrophic muscles is required to develop specific anti-inflammatory treatments. Here, inflammation in mdx mice and the more fibrotic utrn+/-;mdx Het model was comprehensively investigated. Unbiased analysis showed that mdx and Het mice contain increased levels of numerous chemokines and cytokines, with further increased in Het mice. Chemokine and chemokine receptor gene expression levels were dramatically increased in 4-week-old dystrophic quadriceps muscles, and to a lesser extent in diaphragm during the early injury phase, and had a small but consistent increase at 8 and 20 weeks. An optimized direct immune cell isolation method prevented loss of up to 90% of macrophages with density-dependent centrifugation previously used for mdx flow cytometry. Het quadriceps contain higher proportions of neutrophils and infiltrating monocytes than mdx, and higher percentages of F4/80Hi, but lower percentages of F4/80Lo cells and patrolling monocytes compared with Het diaphragms. These differences may restrict regenerative potential of dystrophic diaphragms, increasing pathologic severity. Fibrotic and inflammatory gene expression levels are higher in myeloid cells isolated from Het compared with mdx quadriceps, supporting Het mice may represent an improved model for testing therapeutic manipulation of inflammation in DMD.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

Effects of acute inspiratory loading during treadmill running on cerebral, locomotor and respiratory muscle oxygenation in women soccer players.

Respiratory limitation can be a primary mechanism for exercise cessation in female athletes. This study aimed to assess the effects of inspiratory loading (IL) on intercostal muscles (IM), vastus lateralis (VL) and cerebral (Cox) muscles oxygenation in women soccer players during high-intensity dynamic exercise. Ten female soccer players were randomized to perform in order two constant-load tests on a treadmill until the exhaustion time (Tlim) (100 % of maximal oxygen uptake- V˙O2). They breathed freely or against a fixed inspiratory loading (IL) of 41 cm H2O (∼30 % of maximal inspiratory pressure). Oxygenated (Δ[OxyHb]), deoxygenated (Δ[DeoxyHb]), total hemoglobin (Δ[tHb]) and tissue saturation index (ΔTSI) were obtained by NIRs. Also, blood lactate [La-] was obtained. IL significantly reduced Tlim (224 ± 54 vs 78 ± 20; P < 0.05) and increased [La-], V˙O2, respiratory cycles and dyspnea when corrected to Tlim (P < 0.05). IL also resulted in decrease of Δ[OxyHb] of Cox and IM during exercise compared with rest condition. In addition, decrease of Δ[OxyHb] was observed on IM during exercise when contrasted with Sham (P < 0.05). Furthermore, significant higher Δ[DeoxyHb] of IM and significant lower Δ[DeoxyHb] of Cox were observed when IL was applied during exercise in contrast with Sham (P < 0.05). These results were accompanied with significant reduction of Δ[tHb] and ΔTSI of IM and VL when IL was applied (P < 0.05). High-intensity exercise with IL decreased respiratory and peripheral muscle oxygenation with negative impact on exercise performance. However, the increase in ventilatory work did not impact cerebral oxygenation in soccer players.

Inspiratory flow-resistive breathing, respiratory muscle-induced systemic oxidative stress, and diaphragm fatigue in healthy humans.

We questioned whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. Eight young and healthy participants attended the laboratory for four visits on separate days. During the first visit, height, body mass, lung function, and maximal inspiratory mouth and transdiaphragmatic pressure (Pdimax) were assessed. During visits 2-4, participants undertook inspiratory flow-resistive breathing with either no resistance (control) or resistive loads equivalent to 50 and 70% of their Pdimax (Pdimax50% and Pdimax70%) for 30 min. Participants undertook one resistive load per visit, and the order in which they undertook the loads was randomized. Inspiratory muscle pressures were higher (P < 0.05) during the 5th and Final min of Pdimax50% and Pdimax70% compared with control. Plasma F2-isoprostanes increased (P < 0.05) following inspiratory flow-resistive breathing at Pdimax70%. There were no increases in plasma protein carbonyls or total antioxidant capacity. Furthermore, although we evidenced small reductions in transdiapragmaic twitch pressures (PdiTW) after inspiratory flow-resistive breathing at Pdimax50% and Pdimax70%, this was not related to the increase in plasma F2-isoprostanes. Our novel data suggest that it is only when sufficiently strenuous that inspiratory flow-resistive breathing in humans elicits systemic oxidative stress evidenced by elevated plasma F2-isoprostanes, and based on our data, this is not related to a reduction in PdiTW.NEW & NOTEWORTHY We examined whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. It is only when sufficiently strenuous that inspiratory flow-resistive breathing elevates plasma F2-isoprostanes, and our novel data show that this is not related to a reduction in transdiaphragmatic twitch pressure.

Comparative Analyses of mTOR/Akt and Muscle Atrophy-Related Signaling in Aged Respiratory and Gastrocnemius Muscles.

Sarcopenia is the degenerative loss of skeletal muscle mass and function associated with aging and occurs in the absence of any underlying disease or condition. A comparison of the age-related molecular signaling signatures of different muscles has not previously been reported. In this study, we compared the age-related molecular signaling signatures of the intercostal muscles, the diaphragm, and the gastrocnemii using 6-month and 20-month-old rats. The phosphorylation of Akt, ribosomal S6, and Forkhead box protein O1 (FoxO1) in diaphragms significantly increased with age, but remained unchanged in the intercostal and gastrocnemius muscles. In addition, ubiquitin-proteasome degradation, characterized by the levels of MuRF1 and Atrogin-1, did not change with age in all rat muscles. Interestingly, an increase in LC3BII and p62 levels marked substantial blockage of autophagy in aged gastrocnemii but not in aged respiratory muscles. These changes in LC3BII and p62 levels were also associated with a decrease in markers of mitochondrial quality control. Therefore, our results suggest that the age-related signaling events in respiratory muscles differ from those in the gastrocnemii, most likely to preserve the vital functions played by the respiratory muscles.

Aminophylline increases parasternal muscle action in awake canines.

The traditional theophylline bronchodilator, aminophylline, is still widely used, especially in the treatment of COPD. The effects of aminophylline on ventilation and action of the costal diaphragm have been previously defined, but other respiratory muscles - notably the chest wall, are not well determined. Therefore, we investigated the effects of aminophylline on the Parasternal intercostal, a key obligatory inspiratory muscle, examining muscle length, shortening and EMG. We studied 11 awake canines, chronically implanted with sonomicrometer crystals and fine-wire EMG electrodes in the parasternal muscle. Ventilatory parameters, muscle length (shortening), and moving average muscle EMG activity, were measured at baseline and with aminophylline, during resting and hypercapnic stimulated breathing. Experiments were carried out prior to administration of aminophylline (baseline), and 1.5 h after loading and ongoing infusion. Minute ventilation, tidal volume and respiratory frequency all increased significantly with aminophylline, both during resting breathing and at equivalent levels of hypercapnic stimulated breathing. Parasternal baseline muscle length was entirely unchanged with aminophylline. Parasternal shortening increased significantly with aminophylline while corresponding parasternal EMG activity remained constant, consistent with increased contractility. Thus, in awake, intact mammals, aminophylline, in the usual therapeutic range, elicits increased ventilation and increased contractility of all primary inspiratory respiratory muscles, including both chest wall and diaphragm.

Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea.

BACKGROUND: The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. METHODS: Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. RESULTS: Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 ± 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 ± 10% desmin-abnormal muscle fibres vs. 22 ± 6% in patients without swallowing dysfunction, p = 0.002. CONCLUSION: Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

The Effect of Respiratory Muscle Training on the Pulmonary Function, Lung Ventilation, and Endurance Performance of Young Soccer Players.

This study investigated whether the addition of eight weeks of inspiratory muscle training (IMT) to a regular preseason soccer training program, including incremental endurance training (IET), would change pulmonary function, lung ventilation, and aerobic performance in young soccer players. Sixteen club-level competitive junior soccer players (mean age 17.63 ± 0.48 years, height 182 ± 0.05 cm, body mass 68.88 ± 4.48 kg) participated in the study. Participants were randomly assigned into two groups: experimental (n = 8) and control (n = 8). Both groups performed regular preseason soccer training, including endurance workouts as IET. In addition to this training, the experimental group performed additional IMT for eigght weeks with a commercially available respiratory muscle trainer (Threshold IMT), with a total of 80 inhalations (twice per day, five days per week). Pre- and post-intervention tests of pulmonary function, maximal inspiratory pressure, and the Cooper test were implemented. Eight weeks of IMT had a positive impact on expiratory muscle strength (p = 0.001); however, there was no significant effect on respiratory function parameters. The results also indicate increased efficiency of the inspiratory muscles, contributing to an improvement in aerobic endurance, measured by VO2max estimated from running distance in the cardiorespiratory Cooper test (p < 0.005).

Respiratory muscle oxygenation is not impacted by hypoxia during repeated-sprint exercise.

This study aimed to investigate whether exercise hyperpnoea contributes to an impairment of locomotor muscle oxygenation and performance during repeated-sprint exercise in normoxia and hypoxia. Subjects performed ten 10-s sprints, separated by 30 s of passive rest while breathing either a normoxic (21% O2) or hypoxic (15% O2) gas mixture. Muscle oxygenation of the vastus lateralis and intercostal muscles was examined with near-infrared spectroscopy. Sprint and recovery vastus lateralis deoxyhaemoglobin was elevated in hypoxia by 9.2% (90% confidence interval 0.2 to 18.0) and 14.1% (90% CL 4.9 to 23.3%) compared to normoxia, respectively. There were no clear differences in respiratory muscle deoxyhaemoglobin (-0.1%, 90% CL -2.9 to 0.9%) or oxyhaemoglobin (0.9%, 90% CL -0.8 to 2.6%) between conditions. Maintenance of respiratory muscle oxygenation may contribute to the rise of vastus lateralis deoxyhaemoglobin in hypoxia during intermittent sprint cycling. This manuscript presents data which extends the fact that oxygen competition could be a limiting factor of exercise capacity.

Effect of increased inspiratory muscle work on blood flow to inactive and active limbs during submaximal dynamic exercise.

NEW FINDINGS: What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle metaboreflex. Does increased sympathetic vasoconstriction originating from the respiratory musculature elicit a reduction in blood flow to an inactive limb in order to maintain blood flow to an active limb? What is the main finding and its importance? Arm blood flow was reduced whereas leg blood flow was preserved during mild leg exercise with inspiratory resistance. Blood flow to the active limb is maintained via sympathetic control of blood flow redistribution when the respiratory muscle-induced metaboreflex is activated. ABSTRACT: The purpose of this study was to elucidate the effect of increasing inspiratory muscle work on blood flow to inactive and active limbs. Healthy young men (n = 10, 20 ± 2 years of age) performed two bilateral dynamic knee-extension and knee-flexion exercise tests at 40% peak oxygen uptake for 10 min. The trials consisted of spontaneous breathing for 5 min followed by voluntary hyperventilation either with or without inspiratory resistance for 5 min (40% of maximal inspiratory mouth pressure, inspiratory duty cycle of 50% and a breathing frequency of 40 breaths min-1 ). Mean arterial blood pressure was acquired using finger photoplethysmography. Blood flow in the brachial artery (inactive limb) and in the femoral artery (active limb) were monitored using Doppler ultrasound. Mean arterial blood pressure during exercise was higher (P < 0.05) with inspiratory resistance (121 ± 7 mmHg) than without resistance (99 ± 5 mmHg). Brachial artery blood flow increased during exercise without inspiratory resistance (120 ± 31 ml min-1 ) compared with the resting level, whereas it was attenuated with inspiratory resistance (65 ± 43 ml min-1 ). Femoral artery blood flow increased at the onset of exercise and was maintained throughout exercise without inspiratory resistance (2576 ± 640 ml min-1 ) and was unchanged when inspiratory resistance was added (2634 ± 659 ml min-1 ; P > 0.05). These results suggest that sympathetic control of blood redistribution to active limbs is facilitated, in part, by the respiratory muscle-induced metaboreflex.

Preliminary study: comparative effects of lung volume therapy between slow and fast deep-breathing techniques on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, 6-minute walking distance, and quality of life in persons with COPD.

BACKGROUND: Lung volume therapy with the Voldyne® device can improve lung volume and has a nonsignificant benefit on respiratory muscle strength via the slow deep-breathing technique (SDBT); whereas respiratory muscle training with a respiratory muscle trainer via the fast deep-breathing technique (FDBT) has produced a significant improvement in people with COPD. Thus, the aim of this study was to compare the efficiency of lung volume therapy with the Voldyne® device with the SDBT and FDBT on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, walking capacity, and quality of life (QoL) in people with COPD. METHODS: A total of 30 COPD patient volunteers with mild (stage I) to moderate (stage II) severity were randomized into two groups: SDBT (n=15) and FDBT (n=15). Pulmonary function (FVC, FEV1, and FEV1/FVC), maximal inspiratory mouth pressure (PImax), oxidative stress status (total antioxidant capacity [TAC], glutathione [GSH], malondialdehyde [MDA], and nitric oxide [NO]), inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and IL-6), 6-minute walking distance (6MWD), and total clinical COPD questionnaire (CCQ) score were evaluated before and after 4 weeks of training. RESULTS: All the parameters had no statistical difference between the groups before training. The PImax, TAC, IL-6, total QoL score, and 6MWD changed significantly in the SDBT group after the 4-week experiment as compared to those in the pre-experimental period, whereas FVC, FEV1, FEV1%, FEV1/FVC%, PImax, TAC, MDA, NO, TNF-α, IL-6, 6MWD, and total CCQ score changed significantly in the FDBT group as compared to those in the pre-experimental period. The FEV1%, PImax, TNF-α, IL-6, and total CCQ score differed significantly in the FDBT group in the post-experimental period as compared to those in the SDBT group. CONCLUSION: This preliminary study concluded that the application of incentive spirometry with the Voldyne® device via fast deep breathing possibly improved respiratory muscle strength and QoL and reduced inflammatory cytokines, MDA, and NO better than that via slow deep breathing among people with COPD.

Comparações e correlações da intensidade da dor e da força muscular periférica e respiratória no pré e pós-operatório de cirurgia cardíaca / Comparisons and correlations of pain intensity and respiratory and peripheral muscle strength in the pre- and postoperative periods of cardiac surgery

RESUMO Objetivo: Avaliar a força da musculatura respiratória e periférica após cirurgia cardíaca, e comparar as modificações nestas variáveis no terceiro e no sexto dias pós-operatórios. Métodos: Recrutaram-se 46 pacientes, dos quais 29 eram homens, com média de idade de 60,50 anos (DP = 9,20). Foram submetidos à cirurgia de revascularização do miocárdio 36 pacientes, cinco pacientes foram submetidos à substituição de válvula aórtica, e outros cinco à substituição da válvula mitral. Resultados: Observaram-se redução significante da força da musculatura respiratória e periférica, e significante aumento da intensidade da dor no terceiro e no sexto dias pós-operatórios (p < 0,05), exceto para a variável pressão inspiratória máxima. No sexto dia pós-operatório, os valores da pressão inspiratória máxima já tinham nível similar aos do período pré-operatório e aos valores previstos (p > 0,05). Ocorreu associação entre a força da musculatura periférica, especificamente entre a pressão expiratória máxima no pré-operatório (rs = 0,383; p = 0,009), no terceiro dia pós-operatório (rs = 0,468; p = 0,001) e no sexto dia pós-operatório (rs = 0,311; p = 0,037). Os tamanhos de efeitos foram coerentes em nível moderado à grande para força muscular respiratória, escores segundo a escala Medical Research Council e a Escala Visual Analógica, em particular entre a avaliação pré-operatória e a do sexto dia pós-operatório. Conclusão: Após cirurgia cardíaca, ocorre diminuição da força muscular respiratória e periférica. Além disto, a pressão expiratória máxima é a variável mais associada com a força muscular periférica. Essas variáveis, especialmente a força muscular respiratória e periférica, devem ser consideradas pelos profissionais que atuam no ambiente de terapia intensiva.

ABSTRACT Objective: To evaluate respiratory and peripheral muscle strength after cardiac surgery. Additionally, we compared the changes in these variables on the third and sixth postoperative days. Methods: Forty-six patients were recruited, including 17 women and 29 men, with a mean age of 60.50 years (SD = 9.20). Myocardial revascularization surgery was performed in 36 patients, replacement of the aortic valve in 5 patients, and replacement of the mitral valve in 5 patients. Results: A significant reduction in respiratory and peripheral muscle strength and a significant increase in pain intensity were observed on the third and sixth postoperative days (p < 0.05), except for the variable maximal inspiratory pressure; on the sixth postoperative day, maximal inspiratory pressure values were already similar to the preoperative and predicted values (p > 0.05). There was an association between peripheral muscle strength, specifically between maximal expiratory pressure preoperatively (rs = 0.383; p = 0.009), on the third postoperative day (rs = 0.468; p = 0.001) and on the sixth postoperative day (rs = 0.311; p = 0.037). The effect sizes were consistently moderate-to-large for respiratory muscle strength, the Medical Research Council scale and the visual analog scale, in particular between preoperative assessment and the sixth postoperative day. Conclusion: There is a decrease in respiratory and peripheral muscle strength after cardiac surgery. In addition, maximal expiratory pressure is the variable that is most associated with peripheral muscle strength. These variables, especially respiratory and peripheral muscle strength, should be considered by professionals working in the intensive care setting.

Depleted iron stores are associated with inspiratory muscle weakness independently of skeletal muscle mass in men with systolic chronic heart failure.

BACKGROUND: Skeletal and respiratory muscle dysfunction constitutes an important pathophysiological feature of heart failure (HF). We assessed the relationships between respiratory muscle function, skeletal muscle mass, and physical fitness in men with HF with reduced left ventricular ejection fraction (HFrEF), and investigated the hypothesis of whether iron deficiency (ID) contributes to respiratory muscle dysfunction in these patients. METHODS: We examined 53 male outpatients with stable HFrEF without asthma or chronic obstructive pulmonary disease (age: 64 ± 10 years; New York Heart Association [NYHA] class I/II/III: 36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction ≤40%) and 10 middle-aged healthy men (control group). We analysed respiratory muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was measured using dual-energy X-ray absorptiometry), physical fitness (components of Functional Fitness Test for Older Adults), and iron status. RESULTS: MIP, MEP, and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs. healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower in men with HFrEF with vs. without ID. In a multivariable linear regression model lower serum ferritin (but not transferrin saturation) was associated with lower MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In multivariable linear regression models, lower MIP was associated with worse results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and haemoglobin concentration). CONCLUSIONS: In men with HFrEF, low ferritin reflecting depleted iron stores is associated with inspiratory muscle weakness independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates with worse physical fitness independently of either skeletal muscle mass or disease severity.

Deoxygenation of inspiratory muscles during cycling, hyperpnoea and loaded breathing in health and disease: a systematic review.

Assessing inspiratory muscle deoxygenation and blood flow can provide insight into anaerobic stress, recruitment strategies and mechanisms of inspiratory muscle limitation. Therefore, this review aimed to synthesize measurements of inspiratory muscle oxyhaemoglobin (O2 Hb), deoxyhaemoglobin (HHb), blood volume and flow of the inspiratory muscles acquired via near-infrared spectroscopy (NIRS) during cycling, hyperpnoea and loaded breathing in healthy non-athletes, healthy athletes and patients with chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF). Searches were performed on Medline and Medline in-process, EMBASE, Central, Sportdiscus, PubMed and Compendex. Reviewers independently abstracted articles and assessed their quality using the modified Downs and Black checklist. Of the 644 articles identified, 21 met the inclusion criteria. Studies evaluated non-athletes (n = 9), athletes (n = 5), COPD (n = 2) and CHF (n = 5). The sample was 90% male and 73% were non-athletes and athletes. Interventions included cycle ergometry, hyperpnoea, loaded breathing, elbow flexor loading and combined loaded breathing and ergometry. Athletes and patients with CHF or COPD demonstrated deoxygenation of inspiratory accessory muscles that was often an opposite or exaggerated pattern compared to non-athletes. O2 Hb decreased and HHb increased significantly in inspiratory muscles during cycle ergometry and loaded breathing with accentuated changes during combined ergometry and loaded breathing. During different regimens of hyperpnoea or loaded breathing, comparisons of inspiratory muscles demonstrated that the sternocleidomastoid deoxygenated more than the intercostals, parasternals or scalenes. Evaluating inspiratory muscle deoxygenation via NIRS can inform mechanisms of inspiratory muscle limitation in non-athletes, athletes and patients with CHF or COPD.

Comparisons and correlations of pain intensity and respiratory and peripheral muscle strength in the pre- and postoperative periods of cardiac surgery. / Comparações e correlações da intensidade da dor e da força muscular periférica e respiratória no pré e pós-operatório de cirurgia cardíaca.

OBJECTIVE: To evaluate respiratory and peripheral muscle strength after cardiac surgery. Additionally, we compared the changes in these variables on the third and sixth postoperative days. METHODS: Forty-six patients were recruited, including 17 women and 29 men, with a mean age of 60.50 years (SD = 9.20). Myocardial revascularization surgery was performed in 36 patients, replacement of the aortic valve in 5 patients, and replacement of the mitral valve in 5 patients. RESULTS: A significant reduction in respiratory and peripheral muscle strength and a significant increase in pain intensity were observed on the third and sixth postoperative days (p < 0.05), except for the variable maximal inspiratory pressure; on the sixth postoperative day, maximal inspiratory pressure values were already similar to the preoperative and predicted values (p > 0.05). There was an association between peripheral muscle strength, specifically between maximal expiratory pressure preoperatively (rs = 0.383; p = 0.009), on the third postoperative day (rs = 0.468; p = 0.001) and on the sixth postoperative day (rs = 0.311; p = 0.037). The effect sizes were consistently moderate-to-large for respiratory muscle strength, the Medical Research Council scale and the visual analog scale, in particular between preoperative assessment and the sixth postoperative day. CONCLUSION: There is a decrease in respiratory and peripheral muscle strength after cardiac surgery. In addition, maximal expiratory pressure is the variable that is most associated with peripheral muscle strength. These variables, especially respiratory and peripheral muscle strength, should be considered by professionals working in the intensive care setting.

OBJETIVO: Avaliar a força da musculatura respiratória e periférica após cirurgia cardíaca, e comparar as modificações nestas variáveis no terceiro e no sexto dias pós-operatórios. MÉTODOS: Recrutaram-se 46 pacientes, dos quais 29 eram homens, com média de idade de 60,50 anos (DP = 9,20). Foram submetidos à cirurgia de revascularização do miocárdio 36 pacientes, cinco pacientes foram submetidos à substituição de válvula aórtica, e outros cinco à substituição da válvula mitral. RESULTADOS: Observaram-se redução significante da força da musculatura respiratória e periférica, e significante aumento da intensidade da dor no terceiro e no sexto dias pós-operatórios (p < 0,05), exceto para a variável pressão inspiratória máxima. No sexto dia pós-operatório, os valores da pressão inspiratória máxima já tinham nível similar aos do período pré-operatório e aos valores previstos (p > 0,05). Ocorreu associação entre a força da musculatura periférica, especificamente entre a pressão expiratória máxima no pré-operatório (rs = 0,383; p = 0,009), no terceiro dia pós-operatório (rs = 0,468; p = 0,001) e no sexto dia pós-operatório (rs = 0,311; p = 0,037). Os tamanhos de efeitos foram coerentes em nível moderado à grande para força muscular respiratória, escores segundo a escala Medical Research Council e a Escala Visual Analógica, em particular entre a avaliação pré-operatória e a do sexto dia pós-operatório. CONCLUSÃO: Após cirurgia cardíaca, ocorre diminuição da força muscular respiratória e periférica. Além disto, a pressão expiratória máxima é a variável mais associada com a força muscular periférica. Essas variáveis, especialmente a força muscular respiratória e periférica, devem ser consideradas pelos profissionais que atuam no ambiente de terapia intensiva.

Restoration of pharyngeal dilator muscle force in dystrophin-deficient (mdx) mice following co-treatment with neutralizing interleukin-6 receptor antibodies and urocortin 2.

NEW FINDINGS: What is the central question of this study? We previously reported impaired upper airway dilator muscle function in the mdx mouse model of Duchenne muscular dystrophy (DMD). Our aim was to assess the effect of blocking interleukin-6 receptor signalling and stimulating corticotrophin-releasing factor receptor 2 signalling on mdx sternohyoid muscle structure and function. What is the main finding and its importance? The interventional treatment had a positive inotropic effect on sternohyoid muscle force, restoring mechanical work and power to wild-type values, reduced myofibre central nucleation and preserved the myosin heavy chain type IIb fibre complement of mdx sternohyoid muscle. These data might have implications for development of pharmacotherapies for DMD with relevance to respiratory muscle performance. The mdx mouse model of Duchenne muscular dystrophy shows evidence of impaired pharyngeal dilator muscle function. We hypothesized that inflammatory and stress-related factors are implicated in airway dilator muscle dysfunction. Six-week-old mdx (n = 26) and wild-type (WT; n = 26) mice received either saline (0.9% w/v) or a co-administration of neutralizing interleukin-6 receptor antibodies (0.2 mg kg-1 ) and corticotrophin-releasing factor receptor 2 agonist (urocortin 2; 30 µg kg-1 ) over 2 weeks. Sternohyoid muscle isometric and isotonic contractile function was examined ex vivo. Muscle fibre centronucleation and muscle cellular infiltration, collagen content, fibre-type distribution and fibre cross-sectional area were determined by histology and immunofluorescence. Muscle chemokine content was examined by use of a multiplex assay. Sternohyoid peak specific force at 100 Hz was significantly reduced in mdx compared with WT. Drug treatment completely restored force in mdx sternohyoid to WT levels. The percentage of centrally nucleated muscle fibres was significantly increased in mdx, and this was partly ameliorated after drug treatment. The areal density of infiltrates and collagen content were significantly increased in mdx sternohyoid; both indices were unaffected by drug treatment. The abundance of myosin heavy chain type IIb fibres was significantly decreased in mdx sternohyoid; drug treatment preserved myosin heavy chain type IIb complement in mdx muscle. The chemokines macrophage inflammatory protein 2, interferon-γ-induced protein 10 and macrophage inflammatory protein 3α were significantly increased in mdx sternohyoid compared with WT. Drug treatment significantly increased chemokine expression in mdx but not WT sternohyoid. Recovery of contractile function was impressive in our study, with implications for Duchenne muscular dystrophy. The precise molecular mechanisms by which the drug treatment exerts an inotropic effect on mdx sternohyoid muscle remain to be elucidated.