Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD.

Early lactic acidosis during exercise and abnormal skeletal muscle function have been reported in chronic obstructive pulmonary disease (COPD) but a possible relationship between these two abnormalities has not been evaluated. The purpose of this study was to compare and correlate the increase in arterial lactic acid (La) during exercise and the oxidative capacity of the skeletal muscle in nine COPD patients (age = 62 +/- 5 yr, mean +/- SD, FEV1 40 +/- 9% of predicted) and in nine normal subjects of similar age (54 +/- 3 yr). Following a transcutaneous biopsy of the vastus laterialis, each subject performed a stepwise exercise test on an ergocycle up to his or her maximal capacity during which 5-breath averages of oxygen consumption (Vo2), and serial La concentration measurements were obtained. From the muscle biopsy specimen, the activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase were determined. The La/Vo2 relationship during exercise was fitted by an exponential function in the form La = a + bvo2, where be represents the shape of the relationship. The activity of the oxidative enzymes was significantly lower in COPD than in control subjects (22.8 +/- 3.3 versus 36.8 +/- 8.6 mumol/min/g muscle for CS, and 3.1 +/- 1.1 versus 5.5 +/- 1.4 mumol/min/g for HADH, p < 0.0005) and the increase in lactic acid was steeper in COPD (b = 4.3 +/- 2.0 versus 2.1 +/- 0.2 for normal subjects, p = 0.0005). A significant inverse relationship was found between CS, HADH, and b. No difference was found between the two groups for the glycolytic enzymes. We conclude that in COPD the increase in arterial La during exercise is excessive, the oxidative capacity of the skeletal muscle is reduced, and that these two results are interrelated.

[1]  L. Jorfeldt,et al.  Metabolic enzyme activity in the quadriceps femoris muscle in patients with severe chronic obstructive pulmonary disease. , 1995, American journal of respiratory and critical care medicine.

[2]  J. Le Bas,et al.  Muscular metabolism during oxygen supplementation in patients with chronic hypoxemia. , 1993, The American review of respiratory disease.

[3]  W. Evans,et al.  Changes in Skeletal Muscle with Aging: Effects of Exercise Training , 1993, Exercise and sport sciences reviews.

[4]  N. Jones,et al.  Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation. , 1992, The American review of respiratory disease.

[5]  K. Wasserman,et al.  Is the anaerobic threshold truly anaerobic? , 1992, Chest.

[6]  T. Ishizaki,et al.  31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure. , 1992, The European respiratory journal.

[7]  A. Benabid,et al.  Metabolism and aerobic capacity of skeletal muscle in chronic respiratory failure related to chronic obstructive pulmonary disease. , 1992, The European respiratory journal.

[8]  J. Karlsson,et al.  Exercise-limiting factors in respiratory distress. , 1992, Respiration; international review of thoracic diseases.

[9]  R. Casaburi,et al.  Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. , 1991, The American review of respiratory disease.

[10]  C S Houston,et al.  Operation Everest II: adaptations in human skeletal muscle. , 1989, Journal of applied physiology.

[11]  Nicoletta,et al.  Skeletal muscle energetics, acid-base equilibrium and lactate metabolism in patients with severe hypercapnia and hypoxemia. , 1987, Chest.

[12]  G D Swanson,et al.  Blood lactate concentration increases as a continuous function in progressive exercise. , 1987, Journal of applied physiology.

[13]  Belman Mj.  Exercise in chronic obstructive pulmonary disease. , 1986, Clinics in chest medicine.

[14]  B. Whipp,et al.  Bicarbonate buffering of lactic acid generated during exercise. , 1986, Journal of applied physiology.

[15]  W L Beaver,et al.  Improved detection of lactate threshold during exercise using a log-log transformation. , 1985, Journal of applied physiology.

[16]  P D Gollnick,et al.  Effects of disuse on the structure and function of skeletal muscle. , 1983, Medicine and science in sports and exercise.

[17]  E. Newsholme.  Use of Enzyme Activity Measurements in Studies on the Biochemistry of Exercise , 1980 .

[18]  R T Withers,et al.  Muscle respiratory capacity and fiber type as determinants of the lactate threshold. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[19]  B. A. Wilson,et al.  The effects of hypercapnia on metabolic responses to progressive exhaustive work. , 1980, Medicine and science in sports and exercise.

[20]  G. Hedenstierna,et al.  Muscle metabolism in patients with chronic obstructive lung disease and acute respiratory failure. , 1977, Clinical science and molecular medicine.

[21]  M. Lebowitz,et al.  The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. , 1976, The American review of respiratory disease.

[22]  R. Edwards,et al.  Exercise Tolerance in Chronic Airway Obstruction1, 2 , 1971 .

[23]  E Hultman,et al.  Diet, muscle glycogen and physical performance. , 1967, Acta physiologica Scandinavica.

[24]  L. Opie,et al.  The activities of fructose 1,6-diphosphatase, phosphofructokinase and phosphoenolpyruvate carboxykinase in white muscle and red muscle. , 1967, The Biochemical journal.

[25]  Goldman Hi,et al.  Respiratory function tests; normal values at median altitudes and the prediction of normal results. , 1959 .