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.

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.

Muscle oxygenation maintained during repeated-sprints despite inspiratory muscle loading.

A high work of breathing can compromise limb oxygen delivery during sustained high-intensity exercise. However, it is unclear if the same is true for intermittent sprint exercise. This project examined the effect of adding an inspiratory load on locomotor muscle tissue reoxygenation during repeated-sprint exercise. Ten healthy males completed three experiment sessions of ten 10-s sprints, separated by 30-s of passive rest on a cycle ergometer. The first two sessions were "all-out' efforts performed without (CTRL) or with inspiratory loading (INSP) in a randomised and counterbalanced order. The third experiment session (MATCH) consisted of ten 10-s work-matched intervals. Tissue saturation index (TSI) and deoxy-haemoglobin (HHb) of the vastus lateralis and sixth intercostal space was monitored with near-infrared spectroscopy. Vastus lateralis reoxygenation (ΔReoxy) was calculated as the difference from peak HHb (sprint) to nadir HHb (recovery). Total mechanical work completed was similar between INSP and CTRL (effect size: -0.18, 90% confidence limit ±0.43), and differences in vastus lateralis TSI during the sprint (-0.01 ±0.33) and recovery (-0.08 ±0.50) phases were unclear. There was also no meaningful difference in ΔReoxy (0.21 ±0.37). Intercostal HHb was higher in the INSP session compared to CTRL (0.42 ±0.34), whilst the difference was unclear for TSI (-0.01 ±0.33). During MATCH exercise, differences in vastus lateralis TSI were unclear compared to INSP for both sprint (0.10 ±0.30) and recovery (-0.09 ±0.48) phases, and there was no meaningful difference in ΔReoxy (-0.25 ±0.55). Intercostal TSI was higher during MATCH compared to INSP (0.95 ±0.53), whereas HHb was lower (-1.09 ±0.33). The lack of difference in ΔReoxy between INSP and CTRL suggests that for intermittent sprint exercise, the metabolic O2 demands of both the respiratory and locomotor muscles can be met. Additionally, the similarity of the MATCH suggests that ΔReoxy was maximal in all exercise conditions.

High-frequency spinal cord stimulation in a subacute animal model of spinal cord injury.

High-frequency spinal cord stimulation (HF-SCS) applied at the T2 spinal level results in physiologic activation of the inspiratory muscles in C2 spinal-sectioned dogs. Although the bulbo-spinal fibers were cut, they likely survived the duration of acute experiments, and inspiratory muscle activation may have involved stimulation of these fibers. In two anesthetized, C2 paralyzed, intubated, and mechanically ventilated dogs, HF-SCS (300 Hz) was applied at the T2 level. The effectiveness of HF-SCS in generating inspired volume (V) and negative airway pressures (P) was evaluated over a period of 5 days during which time the bulbo-spinal fibers would have degenerated. Because the effectiveness of HF-SCS may be adversely affected by deterioration of these fibers and/or the condition of the animal, low-frequency (50 Hz) SCS (LF-SCS) was also performed and served as a control. All vital signs, oxygen saturation, and end-tidal Pco2 remained stable over the 5-day period. V and P also remained stable over the study period. For example, mean V and P were 771 ± 25 ml and 64 ± 1 cmH2O with HF-SCS (3 mA) during the initial and 674 ± 59 ml and 63 ± 5 cmH2O on the final day. Comparable values during LF-SCS (8 mA) were 467 ± 12 ml and 48 ± 1 cmH2O during the initial and 397 ± 20 ml and 42 ± 2 cmH2O on the final day. Because V and P in response to HF-SCS remained stable over a 5-day period following which the bulbo-spinal fibers would have degenerated, the mechanism of HF-SCS does not depend upon the viability of these tracts. HF-SCS therefore may be a useful method to restore ventilation in chronic ventilator dependent tetraplegics. NEW & NOTEWORTHY This study indicates that the respiratory responses to high-frequency spinal cord stimulation applied at the T2 level results in activation of the inspiratory motoneuron pools via interneuronal circuits and/or the inspiratory motoneurons directly and does not depend upon activation of long descending inspiratory bulbo-spinal fibers. This method therefore, may provide an alternative method to restore ventilation in ventilator dependent spinal cord injured patients.

Intercostal muscle oxygenation during expiratory load breathing at rest.

BACKGROUND: During acute bronchial obstruction, despite a higher work of breathing, blood supply and oxygen availability may be reduced in intercostal muscles because of mechanical constraints. This hypothesis was assessed in healthy subjects breathing with and without expiratory load (ETL). METHODS: Eleven men (24 ± 2 years) breathed at rest for 5 min in unloaded condition and for 20 min through a 20-cmH2O ETL. Tissue saturation index (TSI) and changes (Δ) in concentration of total and oxy-haemoglobin ([tHb] and [O2Hb]) were measured in the seventh intercostal space by near-infrared spectroscopy. RESULTS: [tHb] and [O2Hb] decreased with ETL (-5.16 µM and -3.54 µM; p < 0.05). TSI did not vary. Negative correlations were observed between Δ[O2Hb] and changes in expiratory flow rate (ΔVt/Te) and between ΔTSI and Δ V˙E (r = -0.78 and -0.74; p ≤ 0.01). CONCLUSION: Despite decreases in Hb concentrations, saturation in oxygen was not reduced with ETL in intercostal muscles, suggesting a satisfactory ventilatory and/or hemodynamic arrangement.

Excess VO2 during ramp exercise is positively correlated to intercostal muscles deoxyhemoglobin levels above the gas exchange threshold in young trained cyclists.

We assessed respiratory muscles oxygenation responses during a ramp exercise to exhaustion and further explored their relationship with the non-linear increase of VO2 (VO2 excess) observed above the gas-exchange threshold. Ten male cyclists completed a ramp exercise to exhaustion on an electromagnetically braked cycle-ergometer with a rate of increment of 30Wmin(-1) with continuous monitoring of expired gases (breath-by-breath) and oxygenation status of intercostal muscles. Maximal inspiratory and expiratory pressure measurements were taken at rest and at exhaustion. The VO2 excess represents the difference between VO2max observed and VO2max expected using linear equation between the VO2 and the intensity before gas-exchange threshold. The deoxyhemoglobin remained unchanged until 60% of maximal aerobic power (MAP) and thereafter increased significantly by 37±18% and 40±22% at 80% and 100% of MAP, respectively. Additionally, the amplitude of deoxyhemoglobin increase between 60 and 100% of MAP positively correlated with the VO2 excess (r=0.69, p<0.05). Compared to exercise start, the oxygen tissue saturation index decreased from 80% of MAP (-4.8±3.2%, p<0.05) onwards. At exhaustion, maximal inspiratory and expiratory pressures declined by 7.8±16% and 12.6±10% (both p<0.05), respectively. In summary, our results suggest a significant contribution of respiratory muscles to the VO2 excess phenomenon.

Aminophylline increases respiratory muscle activity during hypercapnia in humans.

BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. RESULTS: Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. CONCLUSION: Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.

Intercostal and forearm muscle deoxygenation during respiratory fatigue in patients with heart failure: potential role of a respiratory muscle metaboreflex

The purpose of this study was to determine the effect of respiratory muscle fatigue on intercostal and forearm muscle perfusion and oxygenation in patients with heart failure. Five clinically stable heart failure patients with respiratory muscle weakness (age, 66±12 years; left ventricle ejection fraction, 34±3%) and nine matched healthy controls underwent a respiratory muscle fatigue protocol, breathing against a fixed resistance at 60% of their maximal inspiratory pressure for as long as they could sustain the predetermined inspiratory pressure. Intercostal and forearm muscle blood volume and oxygenation were continuously monitored by near-infrared spectroscopy with transducers placed on the seventh left intercostal space and the left forearm. Data were compared by two-way ANOVA and Bonferroni correction. Respiratory fatigue occurred at 5.1±1.3 min in heart failure patients and at 9.3±1.4 min in controls (P<0.05), but perceived effort, changes in heart rate, and in systolic blood pressure were similar between groups (P>0.05). Respiratory fatigue in heart failure reduced intercostal and forearm muscle blood volume (P<0.05) along with decreased tissue oxygenation both in intercostal (heart failure, -2.6±1.6%; controls, +1.6±0.5%; P<0.05) and in forearm muscles (heart failure, -4.5±0.5%; controls, +0.5±0.8%; P<0.05). These results suggest that respiratory fatigue in patients with heart failure causes an oxygen demand/delivery mismatch in respiratory muscles, probably leading to a reflex reduction in peripheral limb muscle perfusion, featuring a respiratory metaboreflex.

Intercostal and forearm muscle deoxygenation during respiratory fatigue in patients with heart failure: potential role of a respiratory muscle metaboreflex.

The purpose of this study was to determine the effect of respiratory muscle fatigue on intercostal and forearm muscle perfusion and oxygenation in patients with heart failure. Five clinically stable heart failure patients with respiratory muscle weakness (age, 66 ± 12 years; left ventricle ejection fraction, 34 ± 3%) and nine matched healthy controls underwent a respiratory muscle fatigue protocol, breathing against a fixed resistance at 60% of their maximal inspiratory pressure for as long as they could sustain the predetermined inspiratory pressure. Intercostal and forearm muscle blood volume and oxygenation were continuously monitored by near-infrared spectroscopy with transducers placed on the seventh left intercostal space and the left forearm. Data were compared by two-way ANOVA and Bonferroni correction. Respiratory fatigue occurred at 5.1 ± 1.3 min in heart failure patients and at 9.3 ± 1.4 min in controls (P<0.05), but perceived effort, changes in heart rate, and in systolic blood pressure were similar between groups (P>0.05). Respiratory fatigue in heart failure reduced intercostal and forearm muscle blood volume (P<0.05) along with decreased tissue oxygenation both in intercostal (heart failure, -2.6 ± 1.6%; controls, +1.6 ± 0.5%; P<0.05) and in forearm muscles (heart failure, -4.5 ± 0.5%; controls, +0.5 ± 0.8%; P<0.05). These results suggest that respiratory fatigue in patients with heart failure causes an oxygen demand/delivery mismatch in respiratory muscles, probably leading to a reflex reduction in peripheral limb muscle perfusion, featuring a respiratory metaboreflex.

Is there a competition for oxygen availability between respiratory and limb muscles?

If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (-10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.

O2 saturation in the intercostal space during moderate and heavy constant-load exercise.

To examine the hypothesis that the relationship between minute ventilation (VE) and deoxygenation from the intercostal space (IC) would be steady regardless of exercise protocols, if an increase in O2 consumption of the accessory respiratory muscles with an increase of VE brings about deoxygenation in IC, we measured the relationship between VE and O2 saturation in IC (SO2IC) during a constant-load exercise test (CET), and the relationship was compared with that during a ramp incremental exercise test (RIET). Six male subjects performed RIET. On a different day, the subjects performed a moderate and heavy CET (CET_MOD and CET_HVY, respectively). SO2IC decreased from the start of both CET_MOD and CET_HVY and changed little from 2 min. Moreover, SO2IC was significantly lower during CET_HVY than during CET_MOD. In comparison between RIET and CET_HVY at the similar VE level, SO2IC was significantly higher during CET_HVY than RIET. These results suggest that the decrease in SO2IC was caused not only by an increase in O2 consumption in IC with an increase in VE but also by a decrease in O2 supply.

Neural respiratory drive measured during inspiratory threshold loading and acute hypercapnia in healthy individuals.

Understanding the effects of respiratory load on neural respiratory drive and respiratory pattern are key to understanding the regulation of load compensation in respiratory disease. The aim of the study was to examine and compare the recruitment pattern of the diaphragm and parasternal intercostal muscles when the respiratory system was loaded using two methods. Twelve subjects performed incremental inspiratory threshold loading up to 50% of their maximal inspiratory pressure, and 10 subjects underwent incremental, steady-state hypercapnia to a maximal inspired CO2 of 5%. The diaphragmatic electromyogram (EMGdi) was measured using a multipair oesophageal catheter, and the parasternal intercostal muscle EMG (sEMGpara) was recorded from bipolar surface electrodes positioned in the second intercostal space. The EMGdi and sEMGpara were analysed over the last minute of each increment of both protocols, normalized using the peak EMG recorded during maximal respiratory manoeuvres and expressed as EMG%max. The EMGdi%max and sEMGpara%max increased in parallel during the two loading methods, although EMGdi%max was consistently greater than sEMGpara%max in both conditions, inspiratory threshold loading [bias (SD) 9 (3)%, 95% limits of agreement 4-15%] and hypercapnia [bias (SD) 6 (3)%, 95% limits of agreement -0.05 to 12%]. Inspiratory threshold loading resulted in more pronounced increases in mean (SD) EMGdi%max [10 (7)-45 (28)%] and sEMGpara%max [5.3 (3.1)-40 (28)%] from baseline compared with EMGdi%max [7 (4)-21 (8)%] and sEMGpara%max [4.7 (2.3)-10 (4)%] during hypercapnia, despite comparable levels of ventilation. These data support the use of sEMGpara%max, as a non-invasive alternative to EMGdi%max recorded with an invasive oesophageal electrode catheter, for the quantification of neural respiratory drive. This technique should make evaluation of respiratory muscle function easier to undertake and therefore more readily acceptable in patients with respiratory disease, in whom transduction of neural respiratory drive to pressure generation can be compromised.

[Inflammation and oxidative stress in respiratory and limb muscles of patients with severe sepsis]. / Inflamación y estrés oxidativo en los músculos respiratorios y periféricos de pacientes con sepsis grave.

BACKGROUND AND OBJECTIVE: Oxidative stress and inflammation contribute to the diaphragm contractile dysfunction observed in animal models of sepsis and endotoxemia. In septic patients, molecular events have never been explored in their respiratory muscles. Levels of oxidative stress and inflammation were evaluated in a respiratory muscle, the external intercostal, and a limb muscle, the vastus lateralis, of patients with sepsis. PATIENTS AND METHODS: Levels of oxidized and nitrated proteins, protein adducts of malondialdehyde and hydroxinonenal, antioxidant enzymes catalase and Mn-superoxide dismutase, tumor necrosis factor (TNF)-α, TNF-α receptors i and ii, interleukin (IL)-1 and IL-6, the panleukocyte marker CD18, and fiber type composition were explored using immunoblotting, real time-polymerase chain reaction, and immunohistochemistry in the external intercostal and vastus lateralis of patients with severe sepsis and/or septic shock. RESULTS: Compared to the controls, in septic patients, levels of oxidized and nitrated proteins were increased in the vastus lateralis, but not in the external intercostal, while those of the antioxidant enzymes did not differ, and the proportions and sizes of the muscle fibers were not significantly different in any muscle between patients and controls. CONCLUSIONS: Differences in activity between the respiratory and limb muscles may account for the differential pattern of oxidative stress and inflammation observed among patients with severe sepsis. These findings may have relevant implications for the clinical and therapeutic management of these patients.

Heterogeneous sensitivity of cerebral and muscle tissues to acute normobaric hyperoxia at rest.

The purpose was to investigate the effects of acute normobaric hyperoxia at rest on cerebral, respiratory and leg muscle oxygenation. Ten healthy men were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air and on the other 100% normobaric O(2) for a 2-hour time period. Oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin in the cerebral frontal cortex, and in the intercostal and vastus lateralis muscles were simultaneously monitored with near-infrared spectroscopy. The hyperoxic stimulus promptly increased Δ[O(2)Hb] (~2 µM) and decreased Δ[HHb] (~3.6 µM) in the frontal cortex. These cerebral responses were directly and fully countered by resumption of normoxic air breathing. In contrast, Δ[HHb] significantly decreased due to the acute hyperoxic stimulus in both intercostal and vastus lateralis muscles. The temporal changes in muscle oxygenation were slower compared to those in the cerebral area; and they only partially recovered during the 15-min normoxic-recovery period. Acute supplementation of normobaric O(2) at rest influences cerebral, leg and respiratory muscle oxygenation of healthy individuals, but not in the same manner. Namely, the frontal cortex seems to be more sensitive to hyperoxia than are the skeletal muscle regions.

Restoration of soman-blocked neuromuscular transmission in human and rat muscle by the bispyridinium non-oxime MB327 in vitro.

The standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes is not sufficiently effective against all types of nerve agents. Alternative therapeutic strategies are required and bispyridinium non-oximes, acting as nicotinic antagonists, were identified as promising compounds. A previous study showed that the di(methanesulfonate) salt of the bispyridinium compound MB327 could restore soman-impaired neuromuscular function in vitro and improve survival of sarin, soman and tabun poisoned guinea pigs in vivo. Here, by using the indirect field stimulation technique, the ability of MB327 to counteract soman-impaired neuromuscular transmission was investigated in human intercostal muscle and rat diaphragm preparations. MB327 restored muscle force in a concentration-dependent manner in both species without reactivating soman-inhibited acetylcholinesterase. The therapeutic effect of MB327 could be washed out, indicating a direct effect at the nicotinic receptor level. Also the ability of MB327 to restore respiratory muscle function could be demonstrated for the first time in rat and human tissue. In combination with previous in vitro and in vivo findings MB327 may be considered a promising compound for the treatment of nerve agent poisoning and further studies are needed to identify optimized drug combinations, concentrations and dosing intervals to provide an effective therapy for OP poisoning.

Detection of age-related duplications in mtDNA from human muscles and bones.

Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans.

We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to approximately 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow.

Expression of intermediate filaments at muscle insertions in human fetuses.

Desmin and vimentin are intermediate filaments that play crucial roles in the maturation, maintenance and recovery of muscle fibers and mesenchymal cells. The expression of these proteins has not been investigated extensively in human fetuses. In the present study, we examined the immunohistochemical expression of intermediate filaments in skeletal muscles of the head, neck and thorax in 12 mid-term human fetuses at 9-18 weeks of gestation. We also used immunohistochemistry to localize the expression of the myosin heavy chain and silver impregnation to identify the fetal endomysium. Expression of desmin and vimentin was already detectable in intercostal muscle at 9 weeks, especially at sites of muscle attachment to the perichondrium. At this stage, myosin heavy chain was expressed throughout the muscle fibers and the endomysium had already developed. Beginning with punctate expression, the positive areas became diffusely distributed in the muscle fibers. At 15-18 weeks, intermediate filament proteins were extensively expressed in all of the muscles examined. Expression at the bone-muscle interface was continuous with expression along the intramuscular tendon fibres. These results suggest that the development of intermediate filaments begins in areas of mechanical stress due to early muscle contraction. Their initially punctate distribution, as observed here, probably corresponds to the earliest stage of fetal enthesis formation.

[Inflammatory cytokines and repair factors in the intercostal muscles of patients with severe COPD]. / Citocinas inflamatorias y factores de reparación en los músculos intercostales de pacientes con EPOC grave.

OBJECTIVE: There is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair. PATIENTS AND METHODS: Twenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor alpha [TNF-alpha] and its type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1beta, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis pathways (Pax7, M-cadherin, and MyoD). RESULTS: Expression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-alpha receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7 [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05]). CONCLUSIONS: Expression of TNF-alpha receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD.

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea.

Although reduced blood lactate concentrations ([lac(-)](B)) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac(-)](B) caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (.V(E) max) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% .V(E) max. The IMT group performed 6 weeks of pressure-threshold IMT; the control group performed no IMT. Maximal inspiratory mouth pressure increased (mean +/- SD) 31 +/- 22% following IMT and was unchanged in the control group. Prior to the intervention in the control group, [lac(-)](B) increased from 0.76 +/- 0.24 mmol L(-1) at rest to 1.50 +/- 0.60 mmol L(-1) (P < 0.05) following 10 min volitional hyperpnoea. In the IMT group, [lac(-)](B) increased from 0.85 +/- 0.40 mmol L(-1) at rest to 2.02 +/- 0.85 mmol L(-1) following 10 min volitional hyperpnoea (P < 0.05). After 6 weeks, increases in [lac(-)](B) during volitional hyperpnoea were unchanged in the control group. Conversely, following IMT the increase in [lac(-)](B) during volitional hyperpnoea was reduced by 17 +/- 37% and 25 +/- 34% following 8 and 10 min, respectively (P < 0.05). In conclusion, increases in [lac(-)](B) during volitional hyperpnoea at 85% .V(E) max were attenuated following IMT. These findings suggest that the inspiratory muscles were the source of at least part of this reduction, and provide a possible explanation for some of the IMT-mediated reductions in [lac(-)](B), often observed during whole-body exercise.