Pierre LeBlanc

Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease.

PURPOSE AND METHODS In this study, we examined the fiber-type proportions, cross-sectional areas (CSA), and capillarization from needle biopsies of the vastus lateralis muscle in 20 patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 37 +/- 11% predicted, peak VO2 = 13 +/- 4 mL.min-1.kg-1) and nine age-matched normal subjects (peak VO2 = 33 +/- 7 mL.min-1.kg-1). The effects of endurance training on these parameters were also evaluated in 11 of the 20 patients with COPD. RESULTS The proportion of Type I fiber was smaller in COPD than normals (34 +/- 14% vs 58 +/- 16 in normals, P < 0.0005) with a corresponding increase in Type IIb fiber (P = 0.015). The CSA of Type I, IIa, and IIab fibers was also smaller in COPD. The capillary to fiber ratio tended to be reduced in patients, but this difference did not reach statistical significance (P = 0.15). The number of capillary contact for Type I, IIa, and IIab fibers was significantly reduced in COPD compared with normal subjects (P < 0.05). When corrected for the CSA, this parameter was similar for both groups. After training, peak VO2 increased by 11% (P < 0.05), the fiber-type proportion remained unchanged, and the CSA of Type I and IIa fibers increased by 31 and 21%, respectively (P < 0.05). Although the number of capillary contact for each fiber types increased with training, the capillary to fiber ratio and the number of capillary contact for the different fiber types relative to their CSA remain unchanged. CONCLUSIONS We conclude that in COPD, 1) the vastus lateralis muscle is characterized by a marked decrease in Type I fiber proportion, an increase in Type IIb fiber proportion, a decrease in Type I, IIa, and IIab fiber CSA and by a relatively preserved capillarization; and 2) a 12-wk training program induces a significant increase in Type I and IIa CSA.

Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD

BACKGROUND Enzymatic and histochemical abnormalities of the peripheral muscle may play a role in exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to measure the mitochondrial enzyme activity of the vastus lateralis muscle in patients with COPD and to evaluate the relationship between enzyme activities and functional status. METHODS Fifty seven patients with COPD of mean (SD) age 66 (7) years with forced expiratory volume in one second (FEV1) 39 (15)% predicted and peak oxygen uptake (V˙o 2) of 14 (4) ml/min/kg and 15 normal subjects of similar age were included in the study. Each subject performed a stepwise exercise test up to maximal capacity during which five-breath averages of V˙o 2were measured. Muscle specimens were obtained by percutaneous needle biopsy of the vastus lateralis muscle and the activity of two mitochondrial enzymes (citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH)) was measured. The functional status of the patients was classified according to peakV˙o 2. RESULTS CS and HADH activities were markedly reduced in patients with COPD compared with normal subjects (22.3 (2.7) versus 29.5 (7.3) μmol/min/g muscle (p<0.0001) and 5.1 (2.0) versus 6.7 (1.9) μmol/min/g muscle (p<0.005), respectively). The activity of CS decreased progressively with the deterioration in the functional status while that of HADH was not related to functional status. Using a stepwise regression analysis, percentage predicted functional residual capacity (FRC), the activity of CS, oxygen desaturation during exercise, age, and inspiratory capacity (% pred) were found to be significant determinants of peakV˙o 2. The regression model explained 59% of the variance in peak V˙o 2 (p<0.0001). CONCLUSIONS The oxidative capacity of the vastus lateralis muscle is reduced in patients with moderate to severe COPD compared with normal subjects of similar age. In these individuals the activity of CS correlated significantly with peak exercise capacity and independently of lung function impairment.

Chronic Obstructive Pulmonary Disease: Capillarity and Fiber-Type Characteristics of Skeletal Muscle

BACKGROUND The purpose of this investigation was to compare capillarity and fiber type proportions of the vastus lateralis muscle between patients with chronic obstructive pulmonary disease (COPD) and healthy subjects. METHODS Fifteen male subjects were included in the study (8 COPD: 61.0 +/- 1.8 years [mean +/- SEM]; forced expiratory volume in 1 second 42.0 +/- 2.1% predicted; 7 N: age 54.0 +/- 1.1). Subjects were submitted to a symptom-limited maximal exercise test on ergocycle. After a transcutaneous biopsy of the vastus lateralis muscle, sections were cut 8 to 10 microns thick and stained with the Andersen method for capillarity and Stevens method for fiber typing. RESULTS Patients with COPD had a decrease in peak oxygen consumption compared with healthy subjects (1.2 +/- 0.1 versus 3.0 +/- 0.2 L/min). Number of capillaries per square millimeter was lower in patients with COPD versus healthy subjects (92.6 +/- 16.1 and 213.3 +/- 33.5, P < 0.001); percentages of fiber types were 43.5 +/- 5.5% type I, 56.5 +/- 5.5% type II in COPD, and 56.7 +/- 3.4% type I, 43.2 +/- 3.4% type II in healthy subjects (P < 0.05). In addition, capillaries/fiber ratio was 0.83 +/- 0.05 in COPD, and 1.56 +/- 0.10 in healthy subjects (P < 0.001). CONCLUSION As expected, patients with COPD showed a decrease in exercise capacity. The muscle analysis results indicate that patients with COPD have a greater proportion of type II fibers and a much lower capillaries/fiber ratio than normal subjects. We conclude that COPD adversely affects fiber type and capillarization of the lower limbs. This could be partly caused by deconditioning in these patients.

Peripheral muscle endurance and the oxidative profile of the quadriceps in patients with COPD

Background: Based on previously reported changes in muscle metabolism that could increase susceptibility to fatigue, we speculated that patients with chronic obstructive pulmonary disease (COPD) have reduced quadriceps endurance and that this will be correlated with the proportion of type I muscle fibres and with the activity of oxidative enzymes. Methods: The endurance of the quadriceps was evaluated during an isometric contraction in 29 patients with COPD (mean (SE) age 65 (1) years; forced expiratory volume in 1 second 37 (3)% predicted) and 18 healthy subjects of similar age. The electrical activity of the quadriceps was recorded during muscle contraction as an objective index of fatigue. The time at which the isometric contraction at 60% of maximal voluntary capacity could no longer be sustained was used to define time to fatigue (Tf). Needle biopsies of the quadriceps were performed in 16 subjects in both groups to evaluate possible relationships between Tf and markers of muscle oxidative metabolism (type I fibre proportion and citrate synthase activity). Results: Tf was lower in patients with COPD than in controls (42 (3) v 80 (7) seconds; mean difference 38 seconds (95% CI 25 to 50), p<0.001). Subjects in both groups had evidence of electrical muscle fatigue at the end of the endurance test. In both groups significant correlations were found between Tf and the proportion of type I fibres and citrate synthase activity. Conclusion: Isometric endurance of the quadriceps muscle is reduced in patients with COPD and the muscle oxidative profile is significantly correlated with muscle endurance.

The metabolic syndrome in patients with chronic obstructive pulmonary disease.

PURPOSE This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients who participated in a cardiopulmonary rehabilitation program. The metabolic syndrome is characterized by the presence of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, presence of insulin resistance, and prothrombotic and inflammatory states that predispose to cardiovascular diseases. METHODS Thirty-eight COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16% predicted) and 34 control participants matched for age and gender are included in this study. The criteria for the identification of the metabolic syndrome include 3 or more of the following features: abdominal obesity (waist circumference: > 102 cm in men, > 88 cm in women), triglycerides levels (>or= 1.69 mmol/L), high-density lipoprotein cholesterol levels (< 1.0 mmol/L in men, < 1.3 mmol/L in women), blood pressure (>or= 130/ >or= 85 mm Hg), and fasting glucose levels (>or= 6.1 mmol/L). RESULTS Forty-seven percent of COPD patients and 21% of control participants presented 3 or more determinants of the metabolic syndrome. CONCLUSIONS The presence of metabolic syndrome is frequent in patients with COPD who participated in a cardiopulmonary program. Hence, this population should be considered for screening for the metabolic syndrome.

Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

Background: Because oxidative stress affects muscle function, the underlying mechanism to explain exercise induced peripheral muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD) is clinically relevant. This study investigated whether chronic hypoxaemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated with it. Methods: Nine chronically hypoxaemic and nine non-hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy specimens were taken from the vastus lateralis muscle before and 48 hours after exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor (TNF)-α levels. Results: When both groups were taken together, arterial oxygen pressure was positively correlated with quadriceps endurance time (n = 18, r = 0.57; p<0.05). At rest, quadriceps lipofuscin inclusions were significantly greater in hypoxaemic patients than in non-hypoxaemic patients (2.9 (0.2) v 2.0 (0.3) inclusions/fibre; p<0.05). Exercise induced a greater increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non-hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%, respectively, both p = 0.01). Neutrophil levels were significantly higher in hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2) counts per fibre × 10−3; p<0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF-α was not detected at baseline or after exercise. Conclusion: Chronic hypoxaemia was associated with lower quadriceps endurance time and worsened muscle oxidative stress at rest and after exercise. Increased muscle neutrophil levels could be a source of the increased baseline oxidative damage. The involvement of a muscle inflammatory process in the exercise induced oxidative stress of patients with COPD remains to be shown.

Skeletal muscle microbiopsy: a validation study of a minimally invasive technique

The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease (COPD) is of growing interest, but often requires biopsies, usually with the Bergström technique. The current study was designed to test the validity of a minimally invasive technique: the microbiopsy. In 17 patients with COPD and four normal subjects, two specimens of the vastus lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge needle (microbiopsy) and the other with the Bergström needle. The enzymatic activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin heavy chain (MyoHC) composition were measured for both techniques. The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy. The microbiopsy sample weight reached 55±17 mg. The two techniques showed excellent agreement for CS activity and MyoHC composition. The PFK activity did not differ statistically between the techniques, but the agreement was moderate. The agreement between both biopsy techniques was stable over time. The median (range) fibre number within the microbiopsy specimens was 144 (38–286). In conclusion, the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects, compared with the Bergström technique.

Peripheral Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

Peripheral muscle dysfunction is a common systemic complication of moderate to severe COPD and may contribute to disability, handicap, and premature mortality. In contrast to the lung impairment, which is largely irreversible, peripheral muscle dysfunction is potentially remediable with exercise training, nutritional intervention, oxygen, and anabolic drugs. Therapeutic success is often incomplete, however, and a better understanding of the mechanisms involved in the development of peripheral muscle dysfunction in COPD is needed to help develop innovative and more effective therapeutic strategies.

Six-Minute Walking Versus Shuttle Walking: Responsiveness to Bronchodilation in Chronic Obstructive Pulmonary Disease

Background: The responsiveness of the endurance shuttle walk to functional changes following bronchodilation has recently been reported. The current literature suggests that the 6 min walking test (6MWT) is less responsive to bronchodilation than the endurance shuttle walk. Aim: To compare bronchodilator-induced changes in exercise performance with the 6MWT and the endurance shuttle walk. Methods: In a randomised, double-blind, placebo-controlled, crossover trial, 14 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s (FEV1) 50 (8)% predicted) completed two 6MWTs and two endurance shuttle walks, each preceded by nebulised placebo or 500 μg ipratropium bromide. Cardiorespiratory parameters were monitored during each walking test with a portable telemetric gas analyser. Quadriceps twitch force was measured by magnetic stimulation of the femoral nerve before and after each walking test. Results: The 6 min walking distance did not change significantly after bronchodilation despite a significant increase in FEV1 of 0.18 (0.09) litres (p<0.001). A similar change in FEV1 (0.18 (0.12) litres, p<0.001) was associated with a significant improvement in the distance walked on the endurance shuttle walk (Δdistance ipratropium bromide – placebo  =  144 (219) m, p = 0.03). Quadriceps muscle fatigue was infrequent (<15% of patients) after both walking tests. Conclusion: The endurance shuttle walk is more responsive than the 6MWT for detecting changes in exercise performance following bronchodilation.

Effects of oxygen on lower limb blood flow and O2 uptake during exercise in COPD.

PURPOSE To quantify the effects of acute oxygen supplementation on lower limb blood flow (QLEG), O2 delivery (QO2LEG), and O2 uptake (VO2LEG) during exercise and to determine whether the metabolic capacity of the lower limb is exhausted at peak exercise during room air breathing in patients with COPD. METHODS Oxygen (FIO2 = 0.75) and air were randomly administered to 14 patients with COPD (FEV1: 35 +/- 2% pred, mean +/- SEM) during two symptom-limited incremental cycle exercise tests. Before exercise, a cannula was installed in a radial artery and a thermodilution catheter inserted in the right femoral vein. At each exercise step, five-breath averages of respiratory rate, tidal volume, and ventilation (VE), dyspnea and leg fatigue scores, arterial and venous blood gases, and QLEG were obtained. From these measurements, VO2LEG was calculated. RESULTS Peak exercise capacity increased from 46 +/- 3 W in room air to 59 +/- 5 W when supplemental oxygen was used (P < 0.001). QLEG, QO2LEG, and VO2LEG were greater at peak exercise with O2 than with air (P < 0.05). During submaximal exercise, dyspnea score and VE were significantly reduced with O2 (P < 0.05), whereas QLEG, VO2LEG, and leg fatigue were similar under both experimental conditions. The improvement in peak exercise work rate correlated with the increase in peak QO2LEG (r = 0.66, P < 0.01), peak VO2LEG (r = 0.53, P < 0.05), and reduction in dyspnea at iso-exercise intensity (r = 0.56, P < 0.05). CONCLUSION The improvement in peak exercise capacity with oxygen supplementation could be explained by the reduction in dyspnea at submaximal exercise and the increases in QO2LEG and VO2LEG, which enabled the exercising muscles to perform more external work. These data indicate that the metabolic capacity of the lower limb muscles was not exhausted at peak exercise during room air breathing in these patients with COPD.