MECHANISMS OF DISEASE - ARE OXYGEN-DERIVED FREE-RADICALS INVOLVED IN DIAPHRAGMATIC DYSFUNCTION

On the basis of a review of the literature we can summarize the role of oxygen-derived free radicals in respiratory muscle dysfunction as follows: 1. Oxygen-derived free radicals are produced in tissues as an end result of different metabolic pathways. Antioxidant defenses including the glutathione- redox cycle, Vitamin E and C, and the enzymatic systems such as SOD, CAT, GSH-Px, etc., limit the damage that free radicals can exert in cell membranes. 2. Exercise and other conditions that regulatory or continuously increase skeletal muscle work load, and result in physiologic impairment, generate increased amounts of free radical species. 3. Measurements of lipid peroxidation by-products, and other indirect indices of free-radical generation have been detected in respiratory muscles, particularly the diaphragm, in animal models of respiratory muscle fatigue. These findings have also been confirmed in in vitro studies of isolated muscle strips. 4. Several studies have evaluated the effect of free radical production in inducing diaphragmatic fatigue by means of pretreatment with free radical scavengers in order to attenuate the rate of development of diaphragmatic impairment. In vitro incubation of diaphragm strips or in vivo pretreatment with free radical scavengers (PEG-SOD, DMSO, Lazeroids, etc.) resulted in a reduction in the rate at which diaphragm fatigue developed in response to oxidative stress. 5. Free-radical-mediated direct injury may be responsible for the development of respiratory muscle dysfunction during systemic infections or the sepsis syndrome.