Prolonged mechanical ventilation (MV) results in reduced diaphrag-matic maximal force production and diaphragmatic atrophy. To investigate the mechanisms responsible for MV-induced diaphrag-matic atrophy, we tested the hypothesis that controlled MV results in oxidation of diaphragmatic proteins and increased diaphrag-matic proteolysis due to elevated protease activity. Further, we postulated that MV would result in atrophy of all diaphragmatic muscle fiber types. Mechanically ventilated animals were anesthe-tized, tracheostomized, and ventilated with 21% O2 for 18 hours. MV resulted in a decrease (p � 0.05) in diaphragmatic myofibrillar protein and the cross-sectional area of all muscle fiber types (i.e., I, IIa, IId/x, and IIb). Further, MV promoted an increase (p � 0.05) in diaphragmatic protein degradation along with elevated (p � 0.05) calpain and 20S proteasome activity. Finally, MV was also associated with a rise (p � 0.05) in both protein oxidation and lipid peroxidation. These data support the hypothesis that MV is associated with atrophy of all diaphragmatic fiber types, increased diaphragmatic protease activity, and augmented diaphragmatic ox-idative stress.

Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species (ROS). Recent evidence suggests that radicals and other ROS are an underlying aetiology in exercise-induced disturbances in muscle redox status. These exercise-induced redox disturbances in skeletal muscle are postulated to contribute to both muscle fatigue and/or exercise-induced muscle injury. To defend against ROS, muscle cells contain complex cellular defence mechanisms to reduce the risk of oxidative injury. Two major classes (enzymic and non-enzymic) of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell. Primary antioxidant enzymes include superoxide dismutase (EC 1.15.1.1; SOD), GSH peroxidase (EC 1.11.1.9; GPX), and catalase (EC 1.11.1.6); these enzymes are responsible for removing superoxide radicals, H2O2 and organic hydroperoxides, and H2O2 respectively. Important non-enzymic antioxidants include vitamins E and C, β-carotene, GSH and ubiquinones. Vitamin E, β-carotene and ubiquinone are located in lipid regions of the cell, whereas GSH and vitamin C are in aqueous compartments of the cell. Regular endurance training promotes an increase in both total SOD and GPX activity in actively-recruited skeletal muscles. High-intensity exercise training has been shown to be generally superior to low-intensity exercise in the upregulation of muscle SOD and GPX activities. Also, training-induced upregulation of antioxidant enzymes is limited to highly-oxidative skeletal muscles. The effects of endurance training on non-enzymic antioxidants remain a relatively uninvestigated area.