Essential Amino Acid Ingestion Facilitates Leucine Retention and Attenuates Myofibrillar Protein Breakdown following Bodyweight Resistance Exercise in Young Adults in a Home-Based Setting

Home-based resistance exercise (RE) has become increasingly prevalent, but its effects on protein metabolism are understudied. We tested the effect of an essential amino acid formulation (EAA+: 9 g EAAs, 3 g leucine) and branched-chain amino acids (BCAAs: 6 g BCAAs, 3 g leucine), relative to a carbohydrate (CHO) placebo, on exogenous leucine retention and myofibrillar protein breakdown following dynamic bodyweight RE in a home-based setting. Twelve recreationally active adults (nine male, three female) participated in a double-blind, placebo-controlled, crossover study with four trial conditions: (i) RE and EAA+ (EX-EAA+); (ii) RE and BCAAs (EX-BCAA); (iii) RE and CHO placebo (EX-CHO); and (iv) rest and CHO placebo (REST-CHO). Total exogenous leucine oxidation and retention (estimates of whole-body anabolism) and urinary 3-methylhistidine:creatinine ratio (3MH:Cr; estimate of muscle catabolism) were assessed over 5 h post-supplement. Total exogenous leucine oxidation and retention in EX-EAA+ and EX-BCAA did not significantly differ (p = 0.116) but were greater than EX-CHO (p < 0.01). There was a main effect of condition on urinary 3MH:Cr (p = 0.034), with post hoc analysis revealing a trend (p = 0.096) for reduced urinary 3MH:Cr with EX-EAA+ (32%) compared to EX-CHO. By direct comparison, urinary 3MH:Cr was significantly lower (23%) in EX-EAA+ than EX-BCAA (p = 0.026). In summary, the ingestion of EAA+ or BCAA provided leucine that was ~60% retained for protein synthesis following home-based bodyweight RE, but EAA+ most effectively attenuated myofibrillar protein breakdown

Effect of inhaled nebulized furosemide on breathlessness during exercise in the setting of abnormal restrictive constraints on tidal colume expansion: a randomized, double blind, placebo contolled, crossover, dose-response study

Introduction: The worldwide prevalence of physical activity-related breathlessness among adults aged 40 years and older is ~27%, with this value expected to rise into the future as our population continues to age. In adults with advanced disease across a range of both malignant and non-malignant diagnoses (e.g., chronic obstructive pulmonary disease, interstitial lung disease, cancer), physical activity-related breathlessness is the hallmark symptom as well as an independent predictor of adverse health outcomes, including exercise intolerance, hospitalization and death. Many of these patients suffer from chronic breathlessness syndrome: breathlessness that persists despite optimal treatment of the underlying pathophysiology and that results in disability. It follows that alleviating breathlessness is amongst the primary goals in the medical management of these individuals. However, there is currently no formal pharmacotherapeutic strategy to manage chronic breathlessness syndrome. Experimental and clinical research suggests that inhalation of the diuretic furosemide can alleviate breathlessness provoked experimentally in health and disease. However, these findings are inconsistent. We reasoned that if inhaled nebulized furosemide relieves breathlessness by mimicking greater VT expansion via altered vagal afferent feedback activity from pulmonary stretch receptors, perhaps it would best accomplish this under conditions of abnormal restrictive constraints on VT expansion in healthy adults.Objective and hypothesis: The primary objective of this study was to examine the acute effect of inhaled nebulized furosemide at doses of 40 mg and 120 mg on ratings of perceived breathlessness during cycle endurance exercise testing in the setting of abnormal restrictive constraints on VT expansion. We hypothesized that single-dose inhalation of nebulized furosemide would be associated with dose-dependent relief of exertional breathlessness compared with nebulized 0.9% saline.Methods: Twenty-four healthy men inhaled nebulized furosemide (40 mg and 120 mg) and nebulized 0.9% saline (placebo) in a randomized, double-blind, placebo-controlled, crossover study. Following inhalation, participants completed a symptom-limited constant-load cycle endurance exercise test at 80% of their peak incremental power output in the setting of external thoracic restriction via chest wall strapping to reduce slow vital capacity by ~20%. Detailed assessments of breathlessness, ventilation, breathing pattern, the behaviour of dynamic operating lung volumes, and cardiometabolic function were performed at rest and during exercise. Diuresis was assessed via post-dose quantification of urine production rate. Results: Compared with nebulized 0.9% saline, neither 40 mg nor 120 mg of inhaled nebulized furosemide had a statistically significant effect on Borg 0-10 scale intensity and unpleasantness ratings of breathlessness during exercise. Similarly, neither dose of inhaled nebulized furosemide had an effect on cardiometabolic, ventilatory, breathing pattern and dynamic operating lung volume responses to exercise compared with placebo. Compared with placebo, a significant effect of 120 mg, but not 40 mg, of nebulized furosemide on urine production rate was observed. No other side effects were reported. Conclusion: Under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 mg and 120 mg did not alleviate the perception of breathlessness during exercise in healthy men.Introduction : La prévalence mondiale de l'essoufflement lié à l'activité physique chez les adultes âgés de 40 ans et plus est de ~ 27 %, avec cette valeur attendue pour s'élever dans l'avenir que notre population continue à vieillir. Chez les adultes atteints d'une maladie avancée dans une gamme de diagnostics malins et non malins (p. ex., la maladie pulmonaire obstructive chronique, la maladie pulmonaire interstitielle, le cancer), l'essoufflement lié à l'activité physique est le symptôme distinctif ainsi qu'un prédicteur indépendant des effets néfastes sur la santé, y compris l'intolérance à l'exercice, l'hospitalisation et la mort. Beaucoup de ces patients souffrent de syndrome de dyspnée chronique : essoufflement qui persiste malgré le traitement optimal de la physiopathologie sous-jacente et qui se traduit par un handicap. Il s'ensuit que la réduction de l'essoufflement est parmi les principaux objectifs de la gestion médicale de ces individus. Cependant, il n'existe actuellement aucune stratégie formelle de pharmacothérapeutique pour gérer le syndrome de l'essoufflement chronique.Des recherches expérimentales et cliniques suggèrent que l'inhalation du furosémide diurétique peut atténuer l'essoufflement provoqué expérimentalement dans la santé et la maladie. Toutefois, ces résultats sont incohérents. Nous avons raisonné que si le furosémide nébulisé inhalé soulage l'essoufflement en imitant une plus grande expansion de VT par l'activité altérée de rétroaction afférente des récepteurs de l'étirement pulmonaire, peut-être qu'il serait mieux d'accomplir ce dans des conditions de contraintes restrictives anormales sur l'expansion du VT chez les adultes en bonne santé.Objectif et hypothèse : L'objectif principal de cette étude était d'examiner l'effet aigu du furosémide nébulisé inhalé à des doses de 40 mg et de 120 mg sur les classements de l'essoufflement perçu pendant l'essai d'endurance de cycle dans le cadre de contraintes restrictives anormales sur l'expansion du VT. Nous avons émis l'hypothèse que l'inhalation d'une dose unique de furosémide nébulisé serait associée à un soulagement dose-dépendante de l'essoufflement de l'effort par rapport à la solution de 0,9 % salin nébulisée.Méthodes : Vingt-quatre hommes sains ont inhalé furosémide (40 mg et 120 mg) et 0,9 % salin nébulisé (placebo) dans une étude randomisée, à double insu, contrôlée par placebo et croisée. À la suite de l'inhalation, les participants ont effectué un essai d'endurance à cycle constant à charge limitée par symptôme à 80 % de leur puissance incrémentale maximum dans le cadre de la restriction thoracique externe par l'intermédiaire du cerclage de la paroi thoracique pour réduire la capacité vitale lente de ~ 20 %. Des évaluations détaillées de l'essoufflement, de la ventilation, de la respiration, du comportement des volumes de poumon d'exploitation dynamique et de la fonction cardiométabolique ont été effectuées au repos et pendant l'exercice. La diurèse a été évaluée par quantification du taux de production d'urine après la dose.Résultats : Comparativement à salins 0,9 % nébulisés, ni 40 mg ni 120 mg de furosémide nébulisé inhalé ont eu un effet statistiquement significatif sur l'intensité de l'échelle de Borg 0-10 et les cotes de désagrément de l'essoufflement pendant l'exercice. De même, aucune dose de furosémide nébulisé inhalée n'a eu d'effet sur la cardiométabolique, la respiration, le modèle respiratoire et les réponses dynamiques du volume pulmonaire à l'exercice par rapport au placebo. Comparativement au placebo, on a observé un effet significatif de 120 mg, mais non de 40 mg, du furosémide nébulisé sur le taux de production d'urine. Aucun autre effet secondaire n'a été rapporté.Conclusion : Dans les conditions expérimentales de cette étude, l'inhalation de furosémide nébulisé à des doses de 40 mg et de 120 mg n'a pas atténué la perception de l'essoufflement pendant l'exercice chez les hommes sains.

Leucine-Enriched Essential Amino Acids Improve Recovery from Post-Exercise Muscle Damage Independent of Increases in Integrated Myofibrillar Protein Synthesis in Young Men

Background: Leucine-enriched essential amino acids (LEAAs) acutely enhance post-exercise myofibrillar protein synthesis (MyoPS), which has been suggested to be important for muscle repair and recovery. However, the ability of LEAAs to concurrently enhance MyoPS and muscle damage recovery in free-living humans has not been studied. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, twenty recreationally active males consuming a controlled diet (1.2 g/kg/d of protein) were supplemented thrice daily with 4 g of LEAAs (containing 1.6 g leucine) or isocaloric placebo for four days following an acute bout of lower-body resistance exercise (RE). MyoPS at rest and integrated over 96 h of recovery was measured by D2O. Isometric and isokinetic torque, muscle soreness, Z-band streaming, muscle heat shock protein (HSP) 25 and 72, plasma creatine kinase (CK), and plasma interleukin-6 (IL-6) were measured over 96 h post-RE to assess various direct and indirect markers of muscle damage. Results: Integrated MyoPS increased ~72% over 96 h after RE (p &lt; 0.05), with no differences between groups (p = 0.98). Isometric, isokinetic, and total peak torque decreased ~21% by 48 h after RE (p &lt; 0.05), whereas total peak torque was ~10% greater overall during recovery in LEAAs compared to placebo (p &lt; 0.05). There were moderate to large effects for peak torque in favour of LEAAs. Muscle soreness increased during recovery with no statistical differences between groups but small to moderate effects in favour of LEAAs that correlated with changes in peak torque. Plasma CK, plasma IL-6, and muscle HSP25 increased after RE (p &lt; 0.05) but were not significantly different between groups (p &ge; 0.13). Consistent with a trend toward attenuated Z-band streaming in LEAAs (p = 0.07), muscle HSP72 expression was lower (p &lt; 0.05) during recovery in LEAAs compared with placebo. There were no correlations between MyoPS and any measures of muscle damage (p &ge; 0.37). Conclusion: Collectively, our data suggest that LEAAs moderately attenuated muscle damage without concomitant increases in integrated MyoPS in the days following an acute bout of resistance exercise in free-living recreationally active men

Leucine-Enriched Essential Amino Acids Improve Recovery from Post-Exercise Muscle Damage Independent of Increases in Integrated Myofibrillar Protein Synthesis in Young Men

Background: Leucine-enriched essential amino acids (LEAAs) acutely enhance post-exercise myofibrillar protein synthesis (MyoPS), which has been suggested to be important for muscle repair and recovery. However, the ability of LEAAs to concurrently enhance MyoPS and muscle damage recovery in free-living humans has not been studied. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, twenty recreationally active males consuming a controlled diet (1.2 g/kg/d of protein) were supplemented thrice daily with 4 g of LEAAs (containing 1.6 g leucine) or isocaloric placebo for four days following an acute bout of lower-body resistance exercise (RE). MyoPS at rest and integrated over 96 h of recovery was measured by D2O. Isometric and isokinetic torque, muscle soreness, Z-band streaming, muscle heat shock protein (HSP) 25 and 72, plasma creatine kinase (CK), and plasma interleukin-6 (IL-6) were measured over 96 h post-RE to assess various direct and indirect markers of muscle damage. Results: Integrated MyoPS increased ~72% over 96 h after RE (p &lt; 0.05), with no differences between groups (p = 0.98). Isometric, isokinetic, and total peak torque decreased ~21% by 48 h after RE (p &lt; 0.05), whereas total peak torque was ~10% greater overall during recovery in LEAAs compared to placebo (p &lt; 0.05). There were moderate to large effects for peak torque in favour of LEAAs. Muscle soreness increased during recovery with no statistical differences between groups but small to moderate effects in favour of LEAAs that correlated with changes in peak torque. Plasma CK, plasma IL-6, and muscle HSP25 increased after RE (p &lt; 0.05) but were not significantly different between groups (p &ge; 0.13). Consistent with a trend toward attenuated Z-band streaming in LEAAs (p = 0.07), muscle HSP72 expression was lower (p &lt; 0.05) during recovery in LEAAs compared with placebo. There were no correlations between MyoPS and any measures of muscle damage (p &ge; 0.37). Conclusion: Collectively, our data suggest that LEAAs moderately attenuated muscle damage without concomitant increases in integrated MyoPS in the days following an acute bout of resistance exercise in free-living recreationally active men

Essential Amino Acid Ingestion Facilitates Leucine Retention and Attenuates Myofibrillar Protein Breakdown following Bodyweight Resistance Exercise in Young Adults in a Home-Based Setting

Home-based resistance exercise (RE) has become increasingly prevalent, but its effects on protein metabolism are understudied. We tested the effect of an essential amino acid formulation (EAA+: 9 g EAAs, 3 g leucine) and branched-chain amino acids (BCAAs: 6 g BCAAs, 3 g leucine), relative to a carbohydrate (CHO) placebo, on exogenous leucine retention and myofibrillar protein breakdown following dynamic bodyweight RE in a home-based setting. Twelve recreationally active adults (nine male, three female) participated in a double-blind, placebo-controlled, crossover study with four trial conditions: (i) RE and EAA+ (EX-EAA+); (ii) RE and BCAAs (EX-BCAA); (iii) RE and CHO placebo (EX-CHO); and (iv) rest and CHO placebo (REST-CHO). Total exogenous leucine oxidation and retention (estimates of whole-body anabolism) and urinary 3-methylhistidine:creatinine ratio (3MH:Cr; estimate of muscle catabolism) were assessed over 5 h post-supplement. Total exogenous leucine oxidation and retention in EX-EAA+ and EX-BCAA did not significantly differ (p = 0.116) but were greater than EX-CHO (p &lt; 0.01). There was a main effect of condition on urinary 3MH:Cr (p = 0.034), with post hoc analysis revealing a trend (p = 0.096) for reduced urinary 3MH:Cr with EX-EAA+ (32%) compared to EX-CHO. By direct comparison, urinary 3MH:Cr was significantly lower (23%) in EX-EAA+ than EX-BCAA (p = 0.026). In summary, the ingestion of EAA+ or BCAA provided leucine that was ~60% retained for protein synthesis following home-based bodyweight RE, but EAA+ most effectively attenuated myofibrillar protein breakdown

Effect of Inhaled Nebulized Furosemide (40 and 120 mg) on Breathlessness during Exercise in the Presence of External Thoracic Restriction in Healthy Men

Inhalation of nebulized furosemide has been shown to alleviate breathlessness provoked experimentally in health and disease; however, it remains unclear whether the efficacy of nebulized furosemide on breathlessness is dose-dependent. We tested the hypothesis that inhaled nebulized furosemide would be associated with a dose-dependent relief of breathlessness during exercise testing in the setting of abnormal restrictive constraints on tidal volume (VT) expansion. In a randomized, double-blind, crossover study, 24 healthy men aged 25.3 ± 1.2 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test in the setting of external thoracic restriction via chest wall strapping to reduce vital capacity by ~20% following single-dose inhalation nebulized furosemide (40 and 120 mg) and 0.9% saline. Compared with 0.9% saline, neither 40 nor 120 mg of inhaled nebulized furosemide had an effect on ratings of perceived breathlessness during exercise or an effect on cardiometabolic, ventilatory, breathing pattern, or dynamic operating lung volume responses during exercise. Urine production rate, the percentage of participants reporting an “urge to urinate” and the intensity of perceived “urge to urinate” were all significantly greater after inhaling the 120 mg furosemide solution compared with both 0.9% saline and 40 mg furosemide solutions. We concluded that, under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 and 120 mg did not alleviate breathlessness during exercise in healthy men