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

Background-Enzymatic and histochemical abnormalities of the peripheral musc le may play a role in exercise intolerance in patients with chronic obstruc tive pulmonary disease (COPD). A study was undertaken to measure the mitoch ondrial enzyme activity of the vastus lateralis muscle in patients with COP D 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 f orced expiratory volume in one second (FEV1) 39 (15)% predicted and peak ox ygen uptake ((V) over dot O-2) of 14 (4) ml/min/kg and 15 normal subjects o f 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) over dot O-2 were measured. Muscle specimens were obtained by percutane ous needle biopsy of the vastus lateralis muscle and the activity of two mi tochondrial enzymes (citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogen ase (HADH)) was measured. The functional status of the patients was classif ied according to peak (V) over dot 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) mu mol/min/g mu scle (p<0.0001) and 5.1 (2.0) versus 6.7 (1.9) mu mol/min/g muscle (p<0.005 ), respectively). The activity of CS decreased progressively with the deter ioration in the functional status while that of HADH was not related to fun ctional 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 s ignificant determinants of peak (V) over dot O-2. The regression model expl ained 59% of the variance in peak (V) over dot O-2 (p<0.0001). Conclusions-The oxidative capacity of the vastus lateralis muscle is reduce d in patients with moderate to severe COPD compared with normal subjects of similar age. In these individuals the activity of CS correlated significan tly with peak exercise capacity and independently of lung function impairme nt.