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Salbutamol is a common short-acting beta2-adrenergic agonist used in treatment of asthma and exercise-induced bronchoconstriction but also possesses anabolic and metabolic actions in skeletal muscle. As a chiral compound, salbutamol is a racemic 1:1 mixture of two enantiomers, (R)-salbutamol and (S)-salbutamol, which exhibit divergent pharmacokinetic and pharmacodynamic actions. Despite salbutamol being available for decades, information on the enantioselective disposition of salbutamol enantiomers in human skeletal muscle is absent. In this study, we determined concentrations of (R)-salbutamol and (S)-salbutamol by UHPLC-MS/MS in arterial plasma and vastus lateralis muscle samples from 12 lean young men 2½ and 7 h following ingestion of 24 mg oral salbutamol. Mean (range) arterial plasma concentrations were 10-fold higher (p < 0.001) for (S)-salbutamol than (R)-salbutamol, being 33(9-62) and 49(30-84) ng·mL-1 for (S)-salbutamol and 4 (1-6) and 4 (2-5) ng·mL-1 for (R)-salbutamol 2½ and 7 h following administration, respectively, reflecting faster elimination of the (R)-enantiomer. Mean (range) muscle concentrations were higher (p < 0.001) for (S)-salbutamol than (R)-salbutamol 2½ h (0.17 [0.1-0.26] vs. 0.04 [0.02-0.06]) and 7 h (0.31 [0.21-0.46] vs. 0.06 [0.04-0.12] ng·mgd.w. -1) after administration. However, muscle:plasma partition coefficient was two-fold higher (p < 0.001) for (R)-salbutamol than (S)-salbutamol 7 h following administration. These observations demonstrate that oral salbutamol exhibits enantioselective disposition in systemic circulation and muscle favoring the (S)-enantiomer but with higher relative partitioning of the (R)-enantiomer in skeletal muscle. Furthermore, the concentration-time profiles of salbutamol enantiomers are different in skeletal muscle and systemic circulation following oral ingestion. These findings have implications for the application of chiral switch (R)-salbutamol in doping control.
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Computer-tomography-guided needle biopsies are useful for diagnosing, staging, and classification of peripheral pulmonary nodules. However, the procedure carries a risk of iatrogenic pneumothorax. This report describes a patient-case where a woman had undergone a computer-tomography guided biopsy. Approximately 4 hours following discharge the patient was admitted to the emergency ward with severe chest pain and dyspnea. Chest x-ray revealed bilateral pneumothorax and subcutaneous emphysema at the biopsy site. Pleural drainage was administered on the patient's right side. Another chest x-ray following drainage showed regression of pneumothorax on both sides thus indicating communicating pleural cavities. Medical history revealed that the patient had been thymectomized 2 years earlier and a computer tomography visualized that the patient lacked mediastinal separation of the two pleural cavities. It is possible that patients with a history of mediastinal or thoracic surgery should be observed longer following procedures carrying risk of iatrogenic pneumothorax.
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PURPOSE: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin ß would increase time trial performance, peak oxygen uptake (VÌO 2peak ), and tHb in both males and females. METHODS: We included 48 healthy, recreational to trained males ( n = 24, mean ± SD VÌO 2peak = 55 ± 5 mL O 2 ·kg -1 â min -1 ) and females ( n = 24; VÌO 2peak of 46 ± 4 mL O 2 ·kg -1 â min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, VÌO 2peak , and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw -1 epoetin ß) or saline (0.9% NaCl) three times weekly for 4 wk. RESULTS: A time-treatment effect ( P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% ( P < 0.001). Likewise, a time-treatment effect ( P < 0.001) existed for VÌO 2peak , where the rHuEPO group improved VÌO 2peak and peak aerobic power by 4.2% ± 6.1% ( P < 0.001) and 2.9% ± 4.0% ( P < 0.01), respectively. A time-treatment effect ( P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% ( P < 0.001). A main effect of "sex" alone was also evident ( P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, VÌO 2peak , peak aerobic power, or tHb. CONCLUSIONS: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.
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Eritropoetina , Consumo de Oxigênio , Masculino , Humanos , Feminino , Exercício Físico , Eritropoetina/farmacologia , Teste de EsforçoRESUMO
Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2 -agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2 -agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg × min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2 -agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.
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Glucose , Resistência à Insulina , Agonistas de Receptores Adrenérgicos beta 2 , Glucose/farmacologia , Hexoquinase/farmacologia , Humanos , Hipertrofia , Insulina/farmacologia , Músculo Esquelético , Poliésteres/farmacologiaRESUMO
This study investigated whether high-intensity exercise training alters the effect of N-acetylcysteine (a precursor of antioxidant glutathione) on exercise-related muscle ionic shifts. We assigned 20 recreationally-active men to 6 weeks of high-intensity exercise training, comprising three weekly sessions of 4-10 × 20-s all-out bouts interspersed by 2 min recovery (SET, n = 10), or habitual lifestyle maintenance (n = 10). Before and after SET, we measured ionic shifts across the working muscle, using leg arteriovenous balance technique, during one-legged knee-extensor exercise to exhaustion with and without N-acetylcysteine infusion. Furthermore, we sampled vastus lateralis muscle biopsies for analyses of metabolites, mitochondrial respiratory function, and proteins regulating ion transport and antioxidant defense. SET lowered exercise-related H+, K+, lactate-, and Na+ shifts and enhanced exercise performance by ≈45%. While N-acetylcysteine did not affect exercise-related ionic shifts before SET, it lowered H+, HCO3-, and Na+ shifts after SET. SET enhanced muscle mitochondrial respiratory capacity and augmented the abundance of Na+/K+-ATPase subunits (α1 and ß1), ATP-sensitive K+ channel subunit (Kir6.2), and monocarboxylate transporter-1, as well as superoxide dismutase-2 and glutathione peroxidase-1. Collectively, these findings demonstrate that high-intensity exercise training not only induces multiple adaptations that enhance the ability to counter exercise-related ionic shifts but also potentiates the effect of N-acetylcysteine on ionic shifts during exercise.
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We investigated the effect of caffeine and acetaminophen on power output during a 6-min performance test, peripheral fatigue, and muscle protein kinase A (PKA) substrate phosphorylation. Fourteen men [age (means ± SD): 26 ± 6 yr; VÌo2max: 63.9 ± 5.0 mL·min-1·kg-1] completed four randomized trials with acetaminophen (1,500 mg), caffeine (5 mg·kg body wt-1), combined caffeine and acetaminophen (caffeine + acetaminophen), or placebo. Mean power output during the 6-min performance test (placebo mean: 312 ± 41 W) was higher with caffeine (+5 W; 95% CI: 1 to 9; P = 0.017) and caffeine + acetaminophen (+6 W; 95% CI: 0 to 12; P = 0.049) than placebo, but not with acetaminophen (+1 W; 95% CI: -4 to 7; P = 0.529). Decline in quadriceps maximal isometric voluntary torque immediately after the performance test was lower (treatment × time; P = 0.035) with acetaminophen (-40 N·m; 95% CI: -53 to -30; P < 0.001) and caffeine + acetaminophen (-44 N·m; 95% CI: -58 to -30; P < 0.001) than placebo (-53 N·m; 95% CI: -71 to -39; P < 0.001) but was similar with caffeine (-54 N·m; 95% CI: -69 to -38; P < 0.001). Muscle phosphocreatine content decreased more during the performance test (treatment × time; P = 0.036) with caffeine + acetaminophen (-55 mmol·kg dry wt-1; 95% CI: -65 to -46; P < 0.001) than placebo (-40 mmol·kg dry wt-1; 95% CI: -52 to -24; P < 0.001). Muscle net lactate accumulation was not different from placebo (+85 mmol·kg dry wt-1; 95% CI: 60 to 110; P < 0.001) for any treatment (treatment × time; P = 0.066), being +75 mmol·kg dry wt-1 (95% CI: 51 to 99; P < 0.001) with caffeine, +76 mmol·kg dry wt-1 (95% CI: 58 to 96; P < 0.001) with acetaminophen, and +103 mmol·kg dry wt-1 (95% CI: 89 to 115; P < 0.001) with caffeine + acetaminophen. Decline in muscle ATP and glycogen content and increase in PKA substrate phosphorylation was not different between treatments (treatment × time; P > 0.1). Thus, acetaminophen provides no additive performance enhancing effect to caffeine during 6-min maximal cycling. In addition, change in PKA activity is likely not a major mechanism of performance improvement with caffeine.NEW & NOTEWORTHY Here, we show that acetaminophen does not provide additive performance improvement to caffeine during a 6-min cycling ergometer performance test, and that acetaminophen does not improve performance on its own. Neither substance affects peripheral fatigue, muscle glycolytic energy production, or phosphorylation of muscle proteins of importance for ion handling. In contrast to previous suggestions, increased epinephrine action on muscle cells does not appear to be a major contributor to the performance enhancement with caffeine.
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Cafeína , Substâncias para Melhoria do Desempenho , Acetaminofen , Método Duplo-Cego , Glicogênio , Humanos , Masculino , Músculo Esquelético , FosfocreatinaRESUMO
AIM: To assess how blood-flow-restricted (BFR) interval-training affects the capacity of the leg muscles for pH regulation during dynamic exercise in physically trained men. METHODS: Ten men (age: 25 ± 4y; VËO2max : 50 ± 5 mLâkg-1 âmin-1 ) completed a 6-wk interval-cycling intervention (INT) with one leg under BFR (BFR-leg; ~180 mmHg) and the other without BFR (CON-leg). Before and after INT, thigh net H+ -release (lactate-dependent, lactate-independent and sum) and blood acid/base variables were measured during knee-extensor exercise at 25% (Ex25) and 90% (Ex90) of incremental peak power output. A muscle biopsy was collected before and after Ex90 to determine pH, lactate and density of H+ -transport/buffering systems. RESULTS: After INT, net H+ release (BFR-leg: 15 ± 2; CON-leg: 13 ± 3; mmol·min-1 ; Mean ± 95% CI), net lactate-independent H+ release (BFR-leg: 8 ± 1; CON-leg: 4 ± 1; mmol·min-1 ) and net lactate-dependent H+ release (BFR-leg: 9 ± 3; CON-leg: 10 ± 3; mmol·min-1 ) were similar between legs during Ex90 (P > .05), despite a ~142% lower muscle intracellular-to-interstitial lactate gradient in BFR-leg (-3 ± 4 vs 6 ± 6 mmol·L-1 ; P < .05). In recovery from Ex90, net lactate-dependent H+ efflux decreased in BFR-leg with INT (P < .05 vs CON-leg) owing to lowered muscle lactate production (~58% vs CON-leg, P < .05). Net H+ gradient was not different between legs (~19%, P > .05; BFR-leg: 48 ± 30; CON-leg: 44 ± 23; mmol·L-1 ). In BFR-leg, NHE1 density was higher than in CON-leg (~45%; P < .05) and correlated with total-net H+ -release (r = 0.71; P = .031) and lactate-independent H+ release (r = 0.74; P = .023) after INT, where arterial [ HCO3- ] and standard base excess in Ex25 were higher in BFR-leg than CON-leg. CONCLUSION: Compared to a training control, BFR-interval training increases the capacity for pH regulation during dynamic exercise mainly via enhancement of muscle lactate-dependent H+ -transport function and blood H+ -buffering capacity.
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Exercício Físico , Ácido Láctico , Adulto , Hemodinâmica , Humanos , Perna (Membro) , Masculino , Músculo Esquelético , Fluxo Sanguíneo RegionalRESUMO
Clenbuterol is a ß2 -agonist prescribed for asthmatic patients in some countries. Based on its anabolic and lipolytic effects observed in studies on rodents and in livestock destined for food production, clenbuterol is abused by bodybuilders and athletes seeking leanness. Urinary clenbuterol analysis is part of routine doping analysis. However, the collection of urine samples is time-consuming and can be intimidating for athletes. Dried blood spot (DBS) appears attractive as an alternative matrix, but the detectability of clenbuterol in humans through DBS has not been investigated. This study evaluated if clenbuterol could be detected in DBS and urine collected from six healthy men after oral intake of 80 µg clenbuterol. The DBS and urine samples were collected at 0, 3, 8, 24, and 72 h post-ingestion, with additional urine collections on days 7 and 10. Using LC-MS/MS, it was shown that clenbuterol could be detected in all DBS samples for 24 h post-ingestion and with 50% sensitivity 3 days after ingestion. The DBS method was 100% specific. Evaluation of analyte stability showed that clenbuterol is stable in DBS for at least 365 days at room temperature when using desiccant and avoiding light exposure. In urine, clenbuterol was detectable for at least 7-10 days after ingestion. Urinary clenbuterol concentrations below 5 ng/mL were present in some subjects 24 h after administration. Collectively, these data indicate that DBS are suitable for routine doping control analysis of clenbuterol with a detection window of at least 3 days after oral administration of 80 µg.
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Agonistas Adrenérgicos beta/sangue , Clembuterol/sangue , Teste em Amostras de Sangue Seco/métodos , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adolescente , Agonistas Adrenérgicos beta/análise , Agonistas Adrenérgicos beta/urina , Adulto , Cromatografia Líquida/métodos , Clembuterol/análise , Clembuterol/urina , Dopagem Esportivo , Estabilidade de Medicamentos , Humanos , Masculino , Espectrometria de Massas em Tandem/métodos , Fatores de Tempo , Adulto JovemRESUMO
KEY POINTS: Endurance-type training with blood flow restriction (BFR) increases maximum oxygen uptake ( VÌO2max ) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. In the present study, we show that BFR-interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally-trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR-training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative-intensity-matched exercise, at the same time as invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR-training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron-transport proteins. Thus, physically trained men benefit from BFR-interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of VÌO2max that can be sustained throughout exercise. ABSTRACT: In the present study, we investigated the effect of training with blood flow restriction (BFR) on thigh oxygen transport and uptake, and lactate release, during exercise. Ten recreationally-trained men (50 ± 5 mL kg-1 min-1 ) completed 6 weeks of interval cycling with one leg under BFR (BFR-leg; pressure: â¼180 mmHg) and the other leg without BFR (CON-leg). Before and after the training intervention (INT), thigh oxygen delivery, extraction, uptake, diffusion capacity and lactate release were determined during knee-extensor exercise at 25% incremental peak power output (iPPO) (Ex1), followed by exercise to exhaustion at 90% pre-training iPPO (Ex2), by measurement of femoral-artery blood flow and femoral-arterial and -venous blood sampling. A muscle biopsy was obtained from legs before and after INT to determine mitochondrial electron-transport protein content. Femoral-artery diameter was also measured. In the BFR-leg, after INT, oxygen delivery and uptake were higher, and net lactate release was lower, during Ex1 (vs. CON-leg; P < 0.05), with an 11% larger increase in workload (vs. CON-leg; P < 0.05). During Ex2, after INT, oxygen delivery was higher, and oxygen extraction was lower, in the BFR-leg compared to the CON-leg (P < 0.05), resulting in an unaltered oxygen uptake (vs. CON-leg; P > 0.05). In the CON-leg, at both intensities, oxygen delivery, extraction, uptake and lactate release remained unchanged (P > 0.05). Resting femoral artery diameter increased with INT only in the BFR-leg (â¼4%; P < 0.05). Oxygen diffusion capacity was similarly raised in legs (P < 0.05). Mitochondrial protein content remained unchanged in legs (P > 0.05). Thus, BFR-interval training enhances oxygen utilization by, and lowers lactate release from, submaximally-exercising muscles of recreationally-trained men mainly by increasing leg convective oxygen transport.
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Consumo de Oxigênio , Coxa da Perna , Artéria Femoral , Humanos , Perna (Membro) , Masculino , Músculo Esquelético/metabolismo , Oxigênio/metabolismo , Fluxo Sanguíneo RegionalRESUMO
Clenbuterol is a beta2 -adrenoceptor agonist marketed as an asthma reliever but is not approved for human use in most countries due to concerns of adverse cardiac effects. Given its demonstrated hypertrophic and lipolytic actions in rodents, clenbuterol is one of the most widely abused doping substances amongt athletes and recreational body-builders seeking leanness. Herein, we examined the effect of clenbuterol ingestion on metabolic rate as well as skeletal muscle mammalian target of rapamycin (mTOR) phosphorylation and protein kinase A (PKA)-signaling in six young men. Before and 140 min after ingestion of 80 µg clenbuterol, resting metabolic rate and contractile function of the quadriceps muscle were measured, and blood samples as well as vastus lateralis muscle biopsies were collected. Clenbuterol increased resting energy expenditure by 21% (P < 0.001), and fat oxidation by 39% (P = 0.006), whereas carbohydrate oxidation was unchanged. Phosphorylation of mTORSer2448 and PKA substrates increased by 121% (P = 0.004) and 35% (P = 0.006), respectively, with clenbuterol. Maximal voluntary contraction torque decreased by 4% (P = 0.026) and the half-relaxation time shortened by 9% (P = 0.046), while voluntary activation, time to peak twitch, and peak twitch torque did not change significantly with clenbuterol. Glycogen content of the vastus lateralis muscle did not change with clenbuterol. Clenbuterol increased circulating levels of glucose (+30%; P < 0.001), lactate (+90%; P = 0.004), insulin (+130%; P = 0.009), and fatty acids (+180%; P = 0.001). Collectively, these findings indicate that clenbuterol is an efficient thermogenic substance that possibly also exerts muscle hypertrophic actions in humans. For these reasons, the restrictions imposed against clenbuterol in competitive sports seem warranted.
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Clembuterol/farmacologia , Metabolismo Energético/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Quadríceps/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Adolescente , Agonistas Adrenérgicos beta/farmacologia , Adulto , Glicemia/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Ácido Láctico/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Potássio/sangue , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
PURPOSE: To investigate the hypothesis that a therapeutic oral dose of Tramadol improves cycling time trial performance and compromises motor-cognitive performance in highly trained cyclists. METHODS: Following two familiarization trials, 16 highly trained cyclists completed a preloaded time trial (1 h at 60% of peak power followed by a 15-km time trial) after ingestion of 100 mg Tramadol or placebo in a double-blind placebo-controlled counterbalanced crossover design separated by at least 4 d washout. Visuomotor tracking and math tasks were completed during the preload (n = 10) to evaluate effects on cognition and fine motor performance. RESULTS: Time trial mean power output (298 ± 42 W vs 294 ± 44 W) and performance (1474 ± 77 s vs 1483 ± 85 s) were similar with Tramadol and placebo treatment, respectively. In addition, there were no differences in perceived exertion, reported pain, blood pH, lactate, or bicarbonate concentrations across trials. Heart rate was higher (P < 0.001) during the Tramadol time trial (171 ± 8 bpm) compared with placebo (167 ± 9 bpm). None of the combined motor-cognitive tasks were impaired by Tramadol ingestion, in fact fine motor performance was slightly improved (P < 0.05) in the Tramadol trial compared with placebo. CONCLUSIONS: In highly trained cyclists, ingestion of 100 mg Tramadol does not improve performance in a 15-km cycling time trial that was completed after a 1-h preload at 60% peak power. Additionally, a therapeutic dose of Tramadol does not compromise complex motor-cognitive or simple fine motor performances.
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Analgésicos Opioides/administração & dosagem , Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Cognição/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos , Tramadol/administração & dosagem , Administração Oral , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/urina , Estudos Cross-Over , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Náusea/induzido quimicamente , Análise e Desempenho de Tarefas , Tramadol/efeitos adversos , Tramadol/urina , Vômito/induzido quimicamente , Adulto JovemRESUMO
This study examined the effects of blood-flow-restricted (BFR)-training on thigh glucose uptake at rest and during exercise in humans and the muscular mechanisms involved. Ten active men (~25â¯y; VO2max ~50â¯mL/kg/min) completed six weeks of training, where one leg trained with BFR (cuff pressure: ~180â¯mmHg) and the other leg without BFR. Before and after training, thigh glucose uptake was determined at rest and during exercise at 25% and 90% of leg incremental peak power output by sampling of femoral arterial and venous blood and measurement of femoral arterial blood flow. Furthermore, resting muscle samples were collected. After training, thigh glucose uptake during exercise was higher than before training only in the BFR-trained leg (pâ¯<â¯0.05) due to increased glucose extraction (pâ¯<â¯0.05). Further, BFR-training substantially improved time to exhaustion during exhaustive exercise (11⯱â¯5% vs. CON-leg; pâ¯=â¯0.001). After but not before training, NAC infusion attenuated (~50-100%) leg net glucose uptake and extraction during exercise only in the BFR-trained leg, which coincided with an increased muscle abundance of Cu/Zn-SOD (39%), GPX-1 (29%), GLUT4 (28%), and nNOS (18%) (pâ¯<â¯0.05). Training did not affect Mn-SOD, catalase, and VEGF abundance in either leg (pâ¯>â¯0.05), although Mn-SOD was higher in BFR-leg vs. CON-leg after training (pâ¯<â¯0.05). The ratios of p-AMPK-Thr172/AMPK and p-ACC-Ser79/ACC, and p-ACC-Ser79, remained unchanged in both legs (pâ¯>â¯0.05), despite a higher p-AMPK-Thr172 in BFR-leg after training (38%; pâ¯<â¯0.05). In conclusion, BFR-training enhances glucose uptake by exercising muscles in humans probably due to an increase in antioxidant function, GLUT4 abundance, and/or NO availability.
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Antioxidantes/metabolismo , Glucose/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Educação Física e Treinamento , Coxa da Perna/fisiologia , Adulto , Dieta , Teste de Esforço , Artéria Femoral/fisiologia , Transportador de Glucose Tipo 4/metabolismo , Humanos , Masculino , Óxido Nítrico/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Descanso/fisiologia , Coxa da Perna/irrigação sanguínea , Adulto JovemRESUMO
The purpose of the present study was to investigate whether exercise training-induced adaptations in human skeletal muscle mitochondrial bioenergetics are magnified under thermal conditions resembling sustained intense contractile activity and whether training-induced changes in mitochondrial oxidative phosphorylation (OXPHOS) efficiency influence exercise efficiency. Twenty healthy men performed 6 wk of high-intensity exercise training [i.e., speed endurance training (SET; n = 10)], or maintained their usual lifestyle (n = 10). Before and after the intervention, mitochondrial respiratory function was determined ex vivo in permeabilized muscle fibers under experimentally-induced normothermia (35°C) and hyperthermia (40°C) mimicking in vivo muscle temperature at rest and during intense exercise, respectively. In addition, activity and content of muscle mitochondrial enzymes and proteins were quantified. Exercising muscle efficiency was determined in vivo by measurements of leg hemodynamics and blood parameters during one-legged knee-extensor exercise. SET enhanced maximal OXPHOS capacity and OXPHOS efficiency at 40°C, but not at 35°C, and attenuated hyperthermia-induced decline in OXPHOS efficiency. Furthermore, SET increased expression of markers of mitochondrial content and up-regulated content of MFN2, DRP1, and ANT1. Also, SET improved exercise efficiency and capacity. These findings indicate that muscle mitochondrial bioenergetics adapts to high-intensity exercise training in a temperature-dependent manner and that enhancements in mitochondrial OXPHOS efficiency may contribute to improving exercise performance.-Fiorenza, M., Lemminger, A. K., Marker, M., Eibye, K., Iaia, F. M., Bangsbo, J., Hostrup, M. High-intensity exercise training enhances mitochondrial oxidative phosphorylation efficiency in a temperature-dependent manner in human skeletal muscle: implications for exercise performance.
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Exercício Físico/fisiologia , Treinamento Intervalado de Alta Intensidade , Músculo Esquelético/fisiologia , Adaptação Fisiológica , Adolescente , Adulto , Metabolismo Energético , Humanos , Técnicas In Vitro , Estudos Longitudinais , Masculino , Mitocôndrias Musculares/fisiologia , Modelos Biológicos , Fibras Musculares Esqueléticas/fisiologia , Fosforilação Oxidativa , Consumo de Oxigênio , Resistência Física/fisiologia , Temperatura , Adulto JovemRESUMO
KEY POINTS: Training with blood flow restriction (BFR) is a well-recognized strategy for promoting muscle hypertrophy and strength. However, its potential to enhance muscle function during sustained, intense exercise remains largely unexplored. In the present study, we report that interval training with BFR augments improvements in performance and reduces net K+ release from contracting muscles during high-intensity exercise in active men. A better K+ regulation after BFR-training is associated with an elevated blood flow to exercising muscles and altered muscle anti-oxidant function, as indicated by a higher reduced to oxidized glutathione (GSH:GSSG) ratio, compared to control, as well as an increased thigh net K+ release during intense exercise with concomitant anti-oxidant infusion. Training with BFR also invoked fibre type-specific adaptations in the abundance of Na+ ,K+ -ATPase isoforms (α1 , ß1 , phospholemman/FXYD1). Thus, BFR-training enhances performance and K+ regulation during intense exercise, which may be a result of adaptations in anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level. ABSTRACT: We examined whether blood flow restriction (BFR) augments training-induced improvements in K+ regulation and performance during intense exercise in men, and also whether these adaptations are associated with an altered muscle anti-oxidant function, blood flow and/or with fibre type-dependent changes in Na+ ,K+ -ATPase-isoform abundance. Ten recreationally-active men (25 ± 4 years, 49.7 ± 5.3 mL kg-1 min-1 ) performed 6 weeks of interval cycling, where one leg trained without BFR (control; CON-leg) and the other trained with BFR (BFR-leg, pressure: â¼180 mmHg). Before and after training, femoral arterial and venous K+ concentrations and artery blood flow were measured during single-leg knee-extensor exercise at 25% (Ex1) and 90% of thigh incremental peak power (Ex2) with i.v. infusion of N-acetylcysteine (NAC) or placebo (saline) and a resting muscle biopsy was collected. After training, performance increased more in BFR-leg (23%) than in CON-leg (12%, P < 0.05), whereas K+ release during Ex2 was attenuated only from BFR-leg (P < 0.05). The muscle GSH:GSSG ratio at rest and blood flow during exercise was higher in BFR-leg than in CON-leg after training (P < 0.05). After training, NAC increased resting muscle GSH concentration and thigh net K+ release during Ex2 only in BFR-leg (P < 0.05), whereas the abundance of Na+ ,K+ -ATPase-isoform α1 in type II (51%), ß1 in type I (33%), and FXYD1 in type I (108%) and type II (60%) fibres was higher in BFR-leg than in CON-leg (P < 0.05). Thus, training with BFR elicited greater improvements in performance and reduced thigh K+ release during intense exercise, which were associated with adaptations in muscle anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level.
Assuntos
Precondicionamento Isquêmico/métodos , Músculo Esquelético/fisiologia , Condicionamento Físico Humano/métodos , Potássio/metabolismo , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Glutationa/metabolismo , Humanos , Infusões Intravenosas , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fluxo Sanguíneo Regional , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
INTRODUCTION: We examined urinary and serum concentrations of formoterol in asthmatic and healthy individuals after a single dose of 18 µg inhaled formoterol and after repeated inhaled doses in healthy individuals. Results were evaluated using the World Anti-Doping Agency (WADA) 2012 threshold for formoterol. METHODS: On the day of this open-label, crossover study, 10 asthmatic subjects who regularly used beta2-agonists and 10 healthy participants with no previous use of beta2-agonists received a single dose of 18 µg formoterol. Further, 10 nonasthmatic participants inhaled 18 µg formoterol every second hour until obtaining a total of 72 µg, which is twice the maximum daily dose (36 µg formoterol) permitted by the WADA. Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 h after the first inhalation. RESULTS: Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 h after inhalation at a maximum of 7.4 ng·mL(-1) in asthmatic subjects and 7.9 ng·mL(-1) in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 h after inhalation of a total of 72 µg formoterol at a maximum of 16.8 ng·mL(-1) in healthy participants. The maximum individual concentration of 25.6 ng·mL(-1) was found after inhalation of a total of 72 µg formoterol. CONCLUSIONS: We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high interindividual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng·mL(-1) formoterol as being an adverse analytical finding.