Aerobic Training in Patients with Congenital Myopathy

INTRODUCTION:Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM. METHODS:Patients exercised on a stationary bike for 30 minutes, three times weekly, for 10 weeks at 70% of their maximal oxygen uptake (VO2max). Creatine kinase (CK) was monitored as a marker of muscle damage. VO2max, functional tests, and questionnaires evaluated efficacy. RESULTS:Sixteen patients with CM were included in a controlled study. VO2max increased by 14% (range, 6-25%; 95% CI 7-20; p < 0.001) in the seven patients who completed training, and tended to decrease in a non-intervention group (n = 7; change -3.5%; range, -11-3%, p = 0.083). CK levels were normal and remained stable during training. Baseline Fatigue Severity Scale scores were high, 4.9 (SE 1.9), and tended to decrease (to 4.4 (SE 1.7); p = 0.08) with training. Nine patients dropped out of the training program. Fatigue was the major single reason. CONCLUSIONS:Ten weeks of endurance training is safe and improves fitness in patients with congenital myopathies. The training did not cause sarcomeric injury, even though sarcomeric function is affected by the genetic abnormalities in most patients with CM. Severe fatigue, which characterizes patients with CM, is a limiting factor for initiating training in CM, but tends to improve in those who train. TRIAL REGISTRATION:The Regional Committee on Health Research Ethics of the Capital Region of Denmark H-2-2013-066 and ClinicalTrials.gov H2-2013-066

Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p &lt; 0.01). Citrate synthase and mitochondrial respiratory chain complex I&ndash;IV activities were increased by 51% and 46&ndash;61%, respectively, in the trained leg (p &lt; 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I&ndash;IV activities by 29&ndash;36% (p &lt; 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA

Skeletal muscle metabolism during prolonged exercise in Pompe disease

Objective: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. Methods: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. Results: In the patients, VO2peak was less than half of average control values; mean difference −1659 mL/min (CI: −2450 to −867, P = 0.001). However, the respiratory exchange ratio increased to >1.0 and lactate levels rose 5-fold in the patients, indicating significant glycolytic flux. In line with this, during submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate were similar between patients and controls (mean difference 0.226 g/min (CI: 0.611 to −0.078, P = 0.318) and mean difference 0.016 μmol/kg/min (CI: 1.287 to −1.255, P = 0.710), respectively). Conclusion: Reflecting muscle weakness and wasting, Pompe disease is associated with markedly reduced maximal exercise capacity. However, glycogenolysis is not impaired in exercise. Unlike in other metabolic myopathies, skeletal muscle substrate use during exercise is normal in Pompe disease rendering exercise less complicated for e.g. medical or recreational purposes

Baseline muscle strength evaluated by MRC score in the seven patients who finished the training program (black bars) and in the nine patients who dropped out of the training program (gray bars).

<p>A significant difference was found between the two groups in three muscle groups; ankle plantar flexion, * p < 0.001; ankle dorsal flexion, ** p = 0.032; hip abduction, *** p = 0.014. Error bars indicate standard error of the mean.</p

Flowchart, maximal oxygen uptake, workload and plasma creatine kinase levels.

<p>(A) 16 patients with CM were included in the study. Four patients from the 1^st training group completed the training program. A non-intervention group of seven CM patients were tested twice, 10 weeks apart, before they participated in the training program (2^nd training group). Only 3 patients from the non-intervention group completed the subsequent training program. In total, nine patients dropped out of the training program. (B) VO_2max before and after 10 weeks of aerobic training in seven CM patients with an improvement corresponding to 215 ml O₂ · min^-1 (CI 121–308 ml O₂ · min^-1, * p = 0.001) (left bars). VO_2max before and after 10 weeks of normal daily living in seven patients with CM (right bars). Black bars represent values before, and gray bars represent values after. The change seen in the intervention group was significant compared to the change in the non-intervention group (mixed Anova, p < 0.001). (C) Maximal workload before and after 10 weeks of aerobic training in seven CM patients who improved W_max by 18 W (CI 11–24 W, ** p = < 0.001) (left bars). W_max before and after 10 weeks of normal daily living in seven CM patients (right bars). Black bars represent values before, and gray bars represent values after. The change seen in the intervention group was significant compared to the change in the non-intervention group (mixed Anova, p < 0.001). (D) Dots represent plasma CK levels at week 0, 3 and 10 from the seven CM patients who finished the training program. All values are within the normal range or slightly elevated when corrected for age and gender. VO_2max: maximal oxygen uptake; CM: congenital myopathy; W_max: maximal workload; CK: creatine kinase.</p