1308 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 166 2002 patch, nor does it require energy from ATP hydrolysis to possibility. Antioxidant supplementation could prevent the development of oxidative stress and consequently attenuate unfold. The reported rise in the level of oxidized proteins in the diaphragm of the ventilated rats (3) could, therefore, muscle proteolysis. This proposal is supported by the observations that vitamin E supplements attenuate immobilizaexplain the need to augment 20S proteasome activity. The development of oxidative stress in limb muscles has tion-induced atrophy in limb muscles (6). In fact, this is what occurs when hibernating animals are immobilized for probeen observed after more than 4 days of disuse and was associated with increased lipid peroxidation and a reduction longed periods of time, yet muscle atrophy doesn’t develop. This is because of a decrease in metabolic rate (and hence in total glutathione (6). The reported rise in protein carbonyls and 8-isoprostane in the diaphragm after only 18 hours of reductioninoxygenradicalformation) andaconcomitantrise in the expression of antioxidant enzymes (10). An additional controlled mechanical ventilation is rather surprising. Controlled mechanical ventilation causes a special form of disuse useful intervention that warrants testing is the prevention of the rise in intracellular calcium with dantrolene (5). Finally, because the diaphragm is being passively shortened by repeated lung inflations. Passive muscle shortening increases future development of tissue-specific proteasome and calpain inhibitors might ameliorate disuse atrophy. blood flow and affects muscle metabolism (7), which might partly explain the different time course of oxidative stress Sabah NA Hussain, MD in the diaphragm versus limb muscles. The mechanisms of ventilator-induced oxidative stress were not explored by Theodoros Vassilakopoulos, MD Shanely and coworkers (3). Limb muscle studies revealed, Meakins-Christie Laboratories however, that disuse is associated with a significant upregula- McGill University tion of superoxide-generating xanthine oxidase (8) and ele- Montreal, Quebec, Canada vated levels of transition metals, including iron, calcium, copper, and manganese (6). The rise in iron is expected to