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 fun ction have been reported in chronic obstructive pulmonary disease (COP D) but a possible relationship between these two abnormalities has not been evaluated. The purpose of this study was to compare and correlat e the increase in arterial lactic acid (La) during exercise and the ox idative capacity of the skeletal muscle in nine COPD patients (age = 6 2 +/- 5 yr, mean +/- SD, FEV(1) 40 +/- 9% of predicted) and in nine no rmal subjects of similar age (54 +/- 3 yr). Following a transcutaneous biopsy of the vastus lateralis, each subject performed a stepwise exe rcise test on an ergocycle up to his or her maximal capacity during wh ich 5-breath averages of oxygen consumption (VO2), and serial La conce ntration measurements were obtained. From the muscle biopsy specimen, the activity of two oxidative enzymes, citrate synthase (CS) and 3-hyd roxyacyl CoA dehydrogenase (HADH), and of three glycolytic enzymes, la ctate dehydrogenase, hexokinase, and phosphofructokinase were determin ed. The La/VO2 relationship during exercise was fitted by an exponenti al function in the form La = a + b(VO2), where b represents the shape of the relationship. The activity of the oxidative enzymes was signifi cantly lower in COPD than in control subjects (22.8 +/- 3.3 versus 36. 8 +/- 8.6 mu mol/min/g muscle for CS, and 3.1 +/- 1.1 versus 5.5 +/- 1 .4 mu mol/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 sub jects, p = 0.0005). A significant inverse relationship was found betwe en CS, HADH, and b. No difference was found between the two groups for the glycolytic enzymes. We conclude that in COPD the increase in arte rial La during exercise is excessive, the oxidative capacity of the sk eletal muscle is reduced, and that these two results are interrelated.