Decreased NADH dehydrogenase and ubiquinol-cytochrome c oxidoreductase in peripheral arterial disease

Peripheral arterial disease (PAD) is associated with muscle metabolic chang es that may contribute to the disability in these patients. However, the bi ochemical defects in PAD have not been identified. The present study was un dertaken to test the hypothesis that PAD is associated with specific defect s in skeletal muscle electron transport chain activity. Seventeen patients with PAD and nine age-matched controls underwent gastrocnemius muscle biops ies. There were no differences in the mitochondrial content per gram of ske letal muscle as assessed by citrate synthase activity between the PAD patie nts and the control subjects. Skeletal muscle NADH dehydrogenase activity w as decreased by 27% compared with controls when expressed per unit of citra te synthase activity. Expression of enzyme activities normalized to cytochr ome c-oxygen oxidoreductase activity confirmed a 26% decrease in NADH dehyd rogenase activity and also demonstrated a 38% decrease in ubiquinol-cytochr ome c oxidoreductase activity. Thus PAD is associated with specific changes in muscle mitochondrial electron transport chain activities characterized by relative decreases in NADH dehydrogenase and ubiquinol-cytochrome c oxid oreductase activities, which may contribute to the metabolic abnormalities and decreased exercise performance in these patients.