Dynamics of cytochrome c oxidase activity in acute ischemic stroke.

We have investigated the dynamics of cytochrome c oxidase (COX) activity in the cerebrospinal fluid (CSF) and the erythrocyte haemolysate (EH) in 85 patients suffering from brain infarction (BI), reversible (RIA), or transient (TIA) ischemic attack from the perspective of mitochondrial affection in ischemia. In all patients, the COX activity was decreased in the CSF, especially within the first two days, indicating an acute inactivation or modification of mitochondrial proteins, probably mediated by free radicals. The gradual elevation of COX activity until the seventh day suggested that these changes may be reversible. The increase in the COX activity was established in the EH, with the highest values found in the BI, somewhat lower in the RIA, and the lowest in the TIA group, respectively. This could indicate a systemic compensatory response to an acute ischemia. Thus, COX activity in the CSF and EH in acute ischemia could be an indicator of brain metabolic dysfunction.

Variation in mitochondrial DNA levels in muscle from normal controls. Is depletion of mtDNA in patients with mitochondrial myopathy a distinct clinical syndrome.

Recent studies have identified a group of patients with cytochrome oxidase (COX) deficiency presenting in infancy associated with a deficiency of mtDNA in muscle or other affected tissue (Moraes et al 1991). We used a novel approach to compare the level of mitochondrial (mtDNA) compared to nuclear DNA in skeletal muscle from a group of patients and controls, based on dot blots that were hybridized with a mtDNA probe labelled with 35S[dCTP] and a reference nuclear DNA probe labelled with [32P]dCTP. The ratio of mtDNA to nuclear DNA varied in samples from different muscles of the same individual. Secondly, fetal muscle had very low levels of mtDNA compared to nuclear DNA, and data from older controls (cross-sectional rather than sequential) suggest that this increases rapidly over the first 3 months after birth and thereafter more slowly. Four patients with COX deficiency had levels of mtDNA that were below the age-specific range defined by 'normal' quadriceps muscle. The clinical features to two of these patients were similar to earlier case reports of mtDNA depletion. In three patients the clinical course was relatively benign compared to cases that have previously been described. Levels of mtDNA in skeletal muscle from some patients with other forms of muscle disease were also found to be low, suggesting that mtDNA depletion, possibly related to depletion of mitochondria, may be a relatively non-specific response of muscle to various pathological processes. However, there does appear to be a distinctive group of young patients with reduced cytochrome oxidase activity in muscle, in whom marked mtDNA depletion reflects the primary defect.