Free radical scavengers and diaphragm injury following inspiratory resistive loading.

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.