MITOCHONDRIAL DISEASE - PULMONARY-FUNCTION, EXERCISE PERFORMANCE, ANDBLOOD LACTATE LEVELS

Mitochondrial diseases are a heterogeneous group of disorders in which it has been suggested that genetic defects in oxidative phosphorylati on lead to specific alterations in exercise performance and lactate me tabolism during exercise. To investigate this possibility, we evaluate d pulmonary function tests, incremental exercise testing, and serial b lood 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 demographi cally comparable and had no significant differences in pulmonary funct ion. Both groups showed similar degrees of reduced exercise tolerance compared with a group of healthy subjects (M: 61.08% predicted Vo(2)ma x +/- 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 nonm itochondrial myopathy subjects (M: 12/13, N: 3/7, H: 3/12, p = 0.002). Minute ventilation greater than predicted occurred with similar frequ ency in both groups. Although resting lactate level was increased in s ome subjects with mitochondrial myopathy compared with disease control s, there were no differences between groups for peak venous lactate le vel normalized for oxygen uptake or the rate of lactate clearance. The se findings, while confirming the presence of some specific abnormalit ies in mitochondrial disease, are against the notion that exercise lim itation in this condition directly results from specific abnormalities in oxidative metabolism.