Satellite Cells Senescence in Limb Muscle of Severe Patients with COPD

Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada Rationale: The maintenance of peripheral muscle mass may be compromised in chronic obstructive pulmonary disease (COPD) due to premature cellular senescence and exhaustion of the regenerative potential of the muscles. Methods: Vastus lateralis biopsies were obtained from patients with COPD (n = 16) and healthy subjects (n = 7). Satellite cell number and the proportion of central nuclei, as a marker of muscle regenerative events, were assessed on cryosections. Telomere lengths, used as a marker of cellular senescence, were determined using Southern blot analyses. Results: Central nuclei proportion was significantly higher in patients with COPD with a preserved muscle mass compared to controls and patients with COPD with muscle atrophy (p,0.001). In COPD, maximal telomere length was significantly decreased compared to controls (p,0.05). Similarly, minimal telomere length was significantly reduced in GOLD III–IV patients with muscle atrophy compared to controls (p,0.005). Minimal, mean and maximum telomere lengths correlated with mid-thigh muscle cross-sectional area (MTCSA) (R = 0.523, p = 0.005; R = 0.435, p = 0.019 and R = 0.491, p = 0.009, respectively). Conclusions: Evidence of increased regenerative events was seen in GOLD III–IV patients with preserved muscle mass. Shortening of telomeres in GOLD III–IV patients with muscle atrophy is consistent with an increased number of senescen

Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

<p>Abstract</p> <p>Background</p> <p>Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3β (GSK-3β), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the <it>vastus lateralis</it>, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2.</p> <p>Results</p> <p>Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins.</p> <p>Conclusions</p> <p>This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.</p

Fatigability of Lower Limb Muscles during Walking in Chronic Obstructive Pulmonary Disease

Background: Patients with chronic obstructive pulmonary disease (COPD) perceive much less quadriceps fatigue during walking compare to cycling. Whether other lower limb muscles could develop fatigue during walking is unknown. The purpose of this study was to assess the electrical activity of five lower limb muscles during a 6-minute walking test in 11 healthy subjects and in 10 patients with COPD matched for age and activity level. Methods: Surface electromyographic (EMG) data were recorded in five muscle groups (soleus, gastrocnemius (GM), tibialis anterior, vastus lateralis and rectus femoris) of the right leg during the walking test. The EMG median frequency of all contractions at minute 2 and 6 were averaged for each muscle group. Ventilation, oxygen consumption and CO2 production were also continuously measured throughout the test. Results: Although the walking distance (494 &#177; 116 vs. 625 &#177; 50 m; P < 0.01) and the walking speed (1.7 &#177; 0.4 vs. 2.1 &#177; 1.2 m&#183;s-1; P < 0.01) were reduced in COPD compared with controls, patients worked at a higher percentage of their estimated maximum voluntary ventilation during the test (118 &#177; 32 % vs. 51 &#177; 14 %; P < 0.01). The time course of the EMG median frequency from minute 2 to 6 differed between patients with COPD and healthy controls for the soleus, GM and tibialis anterior suggesting the occurrence of a muscle fatiguing profile in COPD. Conclusions: Evidences of a fatiguing profile was found in three lower limb muscle groups during walking in COPD despite a slower walking speed compared to healthy controls

Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease

Rationale: The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways. Objectives: To measure the protein expression of AKT, forkhead box class O (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70S6K glycogen synthase kinase-3&szlig; (GSK-3&szlig;), eukaryotic translation initiation factor 4E binding protein-1 (4E-BP1), and the mRNA expression of atrogin-1, muscle ring finger (MuRF) protein 1, and FoxO-1 and -3 in the quadriceps of 12 patients with COPD with muscle atrophy and 10 healthy control subjects. Five patients with COPD with preserved muscle mass were subsequently recruited and were compared with six patients with low muscle mass.Methods: Protein contents and mRNA expression were measured by Western blot and quantitative polymerase chain reaction, respectively.Measurements and Main Results: The levels of atrogin-1 and MuRF1 mRNA, and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins, were increased in patients with COPD with muscle atrophy compared with healthy control subjects, whereas atrogin-1, p70S6K, GSK-3&szlig;, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70S6K, GSK-3&szlig;, and 4E-BP1 compared with patients with COPD with preserved muscle mass.Conclusions: An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps of patients with COPD. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT. The overexpression of the muscle hypertrophic signaling pathways found in patients with COPD with muscle atrophy could represent an attempt to restore muscle mass.<br /

Pulmonary rehabilitation in Canada : A report from the Canadian Thoracic Society COPD Clinical Assembly

BACKGROUND: Pulmonary rehabilitation (PR) is a recommended intervention in the management of individuals with chronic lung disease. It is important to study the characteristics and capacity of programs in Canada to confirm best practices and identify future areas of program improvement and research. OBJECTIVE: To identify all Canadian PR programs, regardless of setting, and to comprehensively describe all aspects of PR program delivery. The present article reports the results of the survey related to type of program, capacity and program characteristics. METHODS: All hospitals in Canada were contacted to identify PR programs. A representative from each program completed a 175-item online survey encompassing 16 domains, 10 of which are reported in the present article. RESULTS: A total of 155 facilities in Canada offered PR, of which 129 returned surveys (83% response rate). PR programs were located in all provinces, but none in the three territories. Most (60%) programs were located in hospital settings, 24% were in public health units and 8% in recreation centres. The national capacity of programs was estimated to be 10,280 patients per year, resulting in 0.4% of all Canadians with chronic obstructive pulmonary disease (COPD) and 0.8% of Canadians with moderate to severe COPD having access to PR. COPD, interstitial lung disease, and asthma were the most common diagnoses of patients. The majority of programs had at least four health care professionals involved; 9% had only one health care professional involved. CONCLUSION: The present comprehensive survey of PR in Canada reports an increase in the number of programs and the total number of patients enrolled since the previous survey in 2005. However, PR capacity has not kept pace with demand, with only 0.4% of Canadians with COPD having access.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofPhysical Therapy, Department ofReviewedFacultyResearche