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.

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F Fu un nc ct ti io on na al l o ou ut tc co om me e o of f p pa at ti ie en nt ts s w wi it th h c ch hr ro on ni ic c o ob bs st tr ru uc ct ti iv ve e p pu ul lm mo on na ar rySixteen stable COPD patients (13 males and 3 females, aged 60±5 yrs, mean±SD) who had previously undergone pulmonary function tests and progressive exercise testing with arterial blood sampling at rest and maximal capacity, entered the study. At first evaluation (E1), subjects were normocapnic at rest (arterial carbon dioxide tension (Pa,CO 2 ): 4.9-5.7 kPa, (37-43 mmHg)) and all presented exercise-induced hypercapnia (end-exercise Pa,CO 2 >5.7 kPa (43 mmHg) with a minimal 0.5 kPa (4 mmHg) increase from resting value). The subjects were re-evaluated 24-54 months later (34±8 months) (second evaluation (E2)).At E2, forced expiratory volume in one second (FEV1) had decreased from 42±13 to 38±15% of predicted values, and mean resting Pa,CO 2 had increased from 5.2±0.3 to 5.7 + 0.4 kPa. Maximal exercise capacity (Wmax) decreased between E1 and E2 from 76±30 to 56±22 W. Even if Wmax was lower at E2, end-exercise Pa,CO 2 was higher than at E1 (6.6±0.8 vs 6.4±0.5 kPa). At E2, eight subjects presented resting hypercapnia (group H), whilst the others remained normocapnic (Group N). Group H subjects had higher Pa,CO 2 , at Wmax than Group N and lower Wmax than Group N at E2. Group H and N were not significantly different for physiological dead space/tidal volume ratio (VD/VT), FEV1, lung volumes and transfer factor of the lungs for carbon monoxide (TL,CO), both at E1 and E2.In half of the patients studied, exercise hypercapnia was a step in the progression of COPD towards resting hypercapnia, and was associated with severe exercise limitation. During exercise, patients who responded to a deterioration in their lung function by increasing minute ventilation remained normocapnic at rest, whilst those who did not increase their ventilation developed chronic hypercapnia at rest during the 2-4 year follow-up period.