Effects of propranolol and exercise training in children with severe burns.
ABSTRACT: To investigate whether propranolol administration blocks the benefits induced by exercise training in severely burned children.Children aged 7-18 years (n = 58) with burns covering ≥30% of the total body surface area were enrolled in this randomized trial during their acute hospital admission. Twenty-seven patients were randomized to receive propranolol, whereas 31 served as untreated controls. Both groups participated in 12 weeks of in-hospital resistance and aerobic exercise training. Muscle strength, lean body mass, and peak oxygen consumption (VO2 peak) were measured before and after exercise training. Paired and unpaired Student t tests were used for within and between group comparisons, and χ(2) tests for nominal data.Age, length of hospitalization, and total body surface area burned were similar between groups. In both groups, muscle strength, lean body mass, and VO2 peak were significantly greater after exercise training than at baseline. The percent change in VO2 peak was significantly greater in the propranolol group than in the control group (P < .05).Exercise-induced enhancements in muscle mass, strength, and VO2 peak are not impaired by propranolol. Moreover, propranolol improves the aerobic response to exercise in massively burned children.
Project description:INTRODUCTION:Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with ?-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo. METHODS:We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V?O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST). RESULTS:Muscle strength and power, lean body mass, and V?O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05). CONCLUSIONS:Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.
Project description:To counteract long-lasting muscle break down, muscle weakness, and poor physical fitness resulting from severe burns, we recommend a 12-week in-hospital exercise training rehabilitation program. Unfortunately, this in-hospital training program requires time away from home, family, school or work. This study was undertaken to evaluate an alternative exercise rehabilitation strategy involving a 12-week community-based exercise training rehabilitation program (COMBEX) carried out at or near the patient and caretaker's home.Pediatric patients (7-18 years) with ? 30% of total body surface area (TBSA) burns were randomized to participate in COMBEX (N=12) or an outpatient exercise program (EX) at the hospital (N=22). Both programs were started after hospital discharge and consisted of 12 weeks of progressive resistive and aerobic exercise. COMBEX was performed in community fitness centers near the patients' home. Endpoints were assessed at discharge (pre-exercise) and after the 12-week program. Primary endpoints were lean body mass (dual energy X-ray absorptiometry), muscle strength (isokinetic dynamometry), and peak aerobic capacity (indirect calorimetry).Demographics, length of hospitalization, and TBSA burned were comparable between groups (P>0.05). Both groups exhibited a significant (P ? 0.01 for all) increase (mean ± SEM) in lean muscle mass (EX: 6.9 ± 1.7%; COMBEX: 6.5 ± 1.1%), muscle strength (EX: 67.1 ± 7.0%; COMBEX: 49.9 ± 6.8%), and peak aerobic capacity (EX: 35.5 ± 4.0%; COMBEX: 46.9 ± 7.7%). Furthermore, the magnitude of these increases were not different between groups (P>0.12).Both EX and COMBEX are efficacious in improving lean mass, strength, and cardiopulmonary capacity in severely burned children.
Project description:Severe burns cause profound hormonal and metabolic disturbances resulting in hypermetabolism, reflected in extreme elevation of resting energy expenditure (REE) and extensive skeletal muscle catabolism. Aerobic and resistive exercise programs during rehabilitation have shown substantial benefits, although whether such training potentially exacerbates basal metabolism is unknown. Therefore, the effects of exercise training on REE during the rehabilitation of severely burned pediatric patients were examined. Children with 40% total body surface area burns and greater were enrolled at admission to the burn intensive care unit to participate in a 12-week, hospital-based exercise program (EX) or a home-based standard of care program (SOC), commencing 6 months after injury. Twenty-one patients (aged 7-17 years) were enrolled and randomized to SOC (n = 10) or EX (n = 11). Age, sex, and total body surface area burned were similar. Mean change (+/-standard deviation) in REE, normalized to individual lean body mass, was almost negligible between SOC and EX group patients (SOC, 0.03 +/- 17.40% vs EX, 0.01 +/- 26.38%). A significant increase in lean body mass was found for EX patients (SOC, 2.06 +/- 3.17% vs EX, 8.75 +/- 5.65%; P = .004), which persisted when normalized to height (SOC, 0.70 +/- 2.39% vs EX, 6.14 +/- 6.46%; P = .02). Peak torque also improved significantly more in EX patients (SOC, 12.29 +/- 16.49% vs EX, 54.31 +/- 44.25%; P = .02), reflecting improved strength. Exercise training significantly enhanced lean mass and strength, without observed exacerbation of postburn hypermetabolism. Therefore, the use of exercise conditioning as a safe and effective component of pediatric burn rehabilitation is advocated.
Project description:INTRODUCTION:To determine whether combined exercise training with an energy-restricted diet leads to improved physical fitness and body composition when compared to energy restriction alone in free-living premenopausal women with clinically severe obesity. METHODS:Sixty premenopausal women (BMI of 40.4 ± 6.7) were randomised to energy restriction only (ER) or to exercise plus energy restriction (EXER) for 12 months. Body composition and fitness were measured at baseline, 3, 6 and 12 months. RESULTS:VO2 peak improved more for EXER compared to ER at 3 (mean difference ± SEM 2.5 ± 0.9 mL ? kg-1 ? min-1, p = 0.006) and 6 (3.1 ± 1.2 mL ? kg-1 ? min-1, p = 0.007) but not 12 months (2.3 ± 1.6 mL ? kg-1 ? min-1, p = 0.15). Muscle strength improved more for EXER compared to ER at all time points. No differences between groups for lean mass were observed at 12 months. CONCLUSION:Combining exercise training with an energy-restricted diet did not lead to greater aerobic power, total body mass, fat mass or limit lean body mass loss at 12 months when compared to energy restriction alone for premenopausal women with clinically severe obesity in free-living situations. Future research should aim to determine an effective lifestyle approach which can be applied in the community setting for this high-risk group.
Project description:Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-based exercise training program on fitness, muscle, and motor function in FSHD patients.Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n?=?8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35?minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention.The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P?=?0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P?=?0.008) and 46% (P?=?0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG.A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.
Project description:BACKGROUND:Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program. METHODS:Previously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod®) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1?), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-?), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships. RESULTS:Exercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO2) correlated with reductions in galectin-3 (r = -0.57, P = 0.05 in RA; r = -0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-? (r < -0.60 and P <0.05 for all). However, the association between increased lean mass and decreased muscle IL-6 association was stronger in prediabetes compared with RA (Fisher r-to-z P = 0.0004); in prediabetes but not RA, lean mass increases occurred in conjunction with reductions in muscle myostatin (r = -0.92; P <0.05; Fisher r-to-z P = 0.026). Subjects who received TNF inhibitors (n = 4) or hydroxychloroquine (n = 4) did not improve body composition with exercise training. CONCLUSION:Exercise responses in muscle myostatin, cytokines, and body composition were significantly greater in prediabetes than in RA, consistent with impaired muscle remodeling in RA. To maximize physiologic improvements with exercise training in RA, a better understanding is needed of skeletal muscle and physiologic responses to exercise training and their modulation by RA disease-specific features or pharmacologic agents or both. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02528344 . Registered on August 19, 2015.
Project description:The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the ?1-, ?2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of oxandrolone and propranolol has added benefit.In this prospective, randomized study of 612 burned children [52%?±?1% of total body surface area burned, ages 0.5-14 years (boys); ages 0.5-12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury.Combined use of oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7?cm/yr (P = 0.0024 vs control).Combined administration of oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.
Project description:Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of ?-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance.In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l-alanyl-l-glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak VO2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1?, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity.The combined supplementation of l-alanyl-l-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534663.
Project description:The purpose of this study was to determine the effects of early outpatient exercise on muscle mass, function, and fractional synthetic rate in severely burned children.Forty-seven children with ?40% total body surface area burn performed a 12-wk standard of care rehabilitation (SOC, n = 23) or rehabilitative exercise training (RET, n = 24) immediately after hospital discharge. Dual-energy x-ray absorptiometry was used to assess lean body mass (LBM) at discharge, posttreatment, and 12 months post-burn. Muscle function was evaluated with a Biodex Isokinetic Dynamometer, and peak aerobic fitness (V?O2peak) was measured using a modified Bruce treadmill protocol posttreatment. Stable isotope infusion studies were performed in a subset of patients (SOC, n = 13; RET, n = 11) at discharge and posttreatment to determine mixed-muscle fractional synthetic rate.Relative peak torque (RET, 138 ± 9 N·m·kg, vs SOC, 106 ± 9 N·m·kg) and V?O2peak (RET, 32 ± 1 mL·kg·min, vs SOC, 28 ± 1 mL·kg·min) were greater at posttreatment with RET compared with those with SOC. In addition, RET increased whole-body (9% ± 2%) and leg (17% ± 3%) LBM compared with SOC. Furthermore, the percentage change in whole-body (18% ± 3%) and leg (31% ± 4%) LBM from discharge to 12 months post-burn was greater with RET compared to SOC. Muscle fractional synthetic rate decreased from discharge to posttreatment in both groups (6.9% ± 1.1% per day vs 3.4 ± 0.4% per day); however, no differences were observed between treatment groups at each time point.Early outpatient exercise training implemented at hospital discharge represents an effective intervention to improve muscle mass and function after severe burn injury.
Project description:PURPOSE:Exercise-induced skeletal muscle deoxygenation is startling by its absence in early post-myocardial infarction (MI) patients. Exercise training early post-MI is associated with reduced cardiovascular risk and increased aerobic capacity. We therefore investigated whether aerobic training could enhance the muscle deoxygenation in early post-MI patients. METHODS:21 ± 8 days after the first MI patients (n = 16) were divided into 12-week aerobic training (TR, n = 10) or non-training (CON, n = 6) groups. Before and after intervention, patients performed ramp bicycle exercise until exhaustion. Muscle deoxygenation was measured at vastus lateralis by near-infrared spectroscopy during exercise. RESULTS:Aerobic training significantly increased peak oxygen uptake (VO2) (18.1 ± 3.0 vs. 22.9 ± 2.8 mL/kg/min), decreased the change in muscle oxygen saturation from rest to submaximal and peak exercise (?SmO2; 2.4 ± 5.7 vs. -7.0 ± 3.4 %), and increased the relative change in deoxygenated hemoglobin/myoglobin concentration from rest to submaximal (-1.5 ± 2.3 vs. 3.0 ± 3.6 ?mol/L) and peak exercise (1.1 ± 4.5 vs. 8.2 ± 3.5 ?mol/L). Change in total hemoglobin/myoglobin concentration in muscle was not significantly affected by training. In CON, no significant alterations were found after 12 weeks in either muscle deoxygenation or peak VO2 (18.6 ± 3.8 vs. 18.9 ± 4.6 mL/kg/min). An increase in peak VO2 was significantly negatively correlated with change in ?SmO2 (r = -0.65) and positively associated with change in ?deoxy-Hb/Mb at peak exercise (r = 0.64) in TR. CONCLUSIONS:In early post-MI patients, aerobic training enhanced skeletal muscle deoxygenation, and the enhancement was related to increased aerobic capacity.