Mitochondrial disease. Pulmonary function, exercise performance, and blood lactate levels.

Mitochondrial diseases are a heterogeneous group of disorders in which it has been suggested that genetic defects in oxidative phosphorylation lead to specific alterations in exercise performance and lactate metabolism during exercise. To investigate this possibility, we evaluated pulmonary function tests, incremental exercise testing, and serial blood lactate levels in a group of subjects with mitochondrial disease (M) and compared them with a group of patients with nonmitochondrial (N) myopathies and healthy subjects (H). The two groups were demographically comparable and had no significant differences in pulmonary function. Both groups showed similar degrees of reduced exercise tolerance compared with a group of healthy subjects (M: 61.08% predicted VO2max +/- 19.58 SD, n = 13; N: 62.14 +/- 28.89, n = 7; H: 115.17 +/- 19.35, n = 12; p < 0.001). The mitochondrial disease group more frequently showed abnormalities in cardiac response to exercise than did the nonmitochondrial myopathy subjects (M: 12/13, N: 3/7, H: 3/12, p = 0.002). Minute ventilation greater than predicted occurred with similar frequency in both groups. Although resting lactate level was increased in some subjects with mitochondrial myopathy compared with disease controls, there were no differences between groups for peak venous lactate level normalized for oxygen uptake or the rate of lactate clearance. These findings, while confirming the presence of some specific abnormalities in mitochondrial disease, are against the notion that exercise limitation in this condition directly results from specific abnormalities in oxidative metabolism.