Effects of exercise on amino acid metabolism in patients with chronic obstructive pulmonary disease.

Depletion of fat-free mass (FFM) significantly contributes to decreased skeletal muscle weakness and impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). FFM wasting suggests disturbances in intermediary metabolism, confirmed by data showing profound alterations in the skeletal muscle amino acid (AA) status in COPD at rest. To unravel whether there is a role for AAs in the mechanisms for skeletal muscle dysfunction in COPD, basic knowledge of AA metabolism in the muscle during exercise is important. We examined the effects of 20 min of exercise on AA metabolism in 14 patients with COPD and eight control subjects. Arterialized venous blood and a quadriceps femoris muscle biopsy were obtained before and immediately after exercise. FFM was not significantly different between the groups. In COPD, a significant reduction of most muscle AAs was present postexercise, whereas several plasma AAs were increased (p < 0.05). Consequently, sum AAs was reduced in muscle (20%; p < 0.01) and increased in plasma (16%, p < 0.05), suggesting an enhanced AA release from muscle in COPD during exercise. In the COPD group, the increase in plasma alanine and glutamine was even higher postexercise (61%, p < 0.01 and 21%, p < 0.01, respectively), suggesting enhanced nitrogen efflux. This study shows that exercise alters amino acid (intermediary) metabolism in patients with COPD and independent of the presence of FFM wasting.

Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease.

Early lactic acidosis has been suggested as negatively influencing the exercise capacity of patients with chronic obstructive pulmonary disease (COPD). We conducted a study to investigate whether the early lactate (La) response to exercise in COPD is related to alterations in exercise-related substrate levels in resting muscle, associated with physical inactivity. Twenty-seven COPD patients and 22 controls (physically inactive [PI] subjects, n = 15; and physically active [PA] subjects, n = 7) performed an incremental cycle test. Venous blood was sampled for La analyses, and the oxygen uptake at which the La level began to rise (La threshold) was calculated. Vastus lateralis biopsy specimens were obtained at rest. In the PA group, muscle glutamate (GLU) and glycogen were higher, but muscle La, pyruvate, and glucose were not different than in the PI group. Moreover, the La threshold was higher in the PA group. The COPD group had lower values for La threshold and muscle GLU, and higher values for muscle La and pyruvate levels than did the PI group. Stratification of patients into those with and without macroscopic emphysema (EMPH+, EMPH-, respectively), with comparable physical activity levels on the basis of previous observations, revealed lower values for La threshold and GLU in EMPH+ patients. Diffusing capacity for carbon monoxide (DL(CO)) and arterial oxygen tension (Pa(O(2))) in the four study groups were positively related to GLU and La threshold. Moreover, La threshold was positively related to GLU. This study illustrates that the early lactic acidosis during exercise in patients with COPD is associated with the physical inactivity-related reduction in these patient's muscle GLU. However, factors other than physical inactivity, such as Pa(O(2)) or DL(CO), play a role in the different La responses during exercise in subjects with different subtypes of COPD.

Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease.

BACKGROUND: Skeletal muscle weakness is a prominent problem in many patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of the study was to determine the relation between skeletal muscle function, body composition, and lung function in COPD (emphysema and chronic bronchitis) patients and healthy volunteers. DESIGN: In 50 patients with chronic bronchitis, 49 patients with emphysema, and 28 healthy volunteers, skeletal muscle function was assessed by handgrip and linear isokinetic dynamometry. Whole-body and subregional fat-free mass (FFM) were assessed by dual-energy X-ray absorptiometry. RESULTS: Whole-body and extremity FFM were significantly lower in patients with emphysema (P < 0.001) and chronic bronchitis (P < 0.05) than in healthy volunteers, but trunk FFM was significantly lower only in patients with emphysema (P < 0.001). Extremity FFM was not significantly different between the COPD subtype groups, despite significantly lower values for whole-body and trunk FFM (P < 0.05) in patients with emphysema. Absolute skeletal muscle function (P < 0. 001) and muscle function per kilogram of whole-body FFM were significantly lower in both COPD subtype groups than in healthy volunteers (P < 0.05), but no significant difference was found between patients with chronic bronchitis and those with emphysema. Muscle function per kilogram of extremity FFM was not significantly different between the 3 groups and was not associated with forced expiratory volume in 1 s. CONCLUSION: Skeletal muscle weakness is associated with wasting of extremity FFM in COPD patients, independent of airflow obstruction and COPD subtype.

Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema.

Chronic obstructive pulmonary disease (COPD) is often characterized by an impaired skeletal muscle energy metabolism, which is at least partly related to chronic hypoxia and a reduced diffusing capacity. We have found that muscle glutamate (Glu), which is negatively influenced by these conditions, was reduced in patients with severe COPD. The aim of this study was to investigate whether the reduced intracellular Glu level in patients with emphysema is associated with an increased muscle glycolytic metabolism. Since Glu is an important substrate in the synthesis of glutamine (Gln) and glutathione (GSH), the influence of Glu status on muscle GSH and Gln was also examined. In 13 patients with emphysema and 25 control patients, arterial blood and biopsies from the vastus lateralis muscle were obtained. Expressed as a percentage of the control values, the patients with emphysema had reduced values for muscle Glu (64 +/- 12%; p < 0.001), GSH (76 +/- 23%; p < 0.01), and Gln (93 +/- 5%; p < 0.01), and higher values for lactate (p < 0.01) and pyruvate (p < 0.05). No differences were found in plasma values. Muscle Glu was highly associated with GSH (R(2) = 0.61; p < 0.001), but not with Gln. This study illustrates that reduced Glu levels in skeletal muscle of patients with emphysema are possibly related to an enhanced glycolytic activity and associated with decreased GSH levels.