EFFECTS OF HYPEROXIA ON RAT DIAPHRAGM FUNCTION

The association of oxygen radical generation with impaired diaphragm p erformance has previously been reported after inspiratory resistive lo ading (IRL). We hypothesized that exposure of rats to normobaric hyper oxia (O-2) could produce impaired diaphragm function because of free r adical production. Sprague-Dawley rats were divided into four groups: 1) room air (control), 2) > 95% O-2 for 24 h, 3) > 95% O-2 for 48 h, a nd 4) > 95% O-2 for 60 h. Each group was studied at rest after the O-2 exposure and then after IRL. During IRL, the animals breathed through an inspiratory resistor until they were unable to sustain > 70% of th e maximum airway pressure. Diaphragm samples were obtained for analysi s of glutathione (GSH) and glutathione disulfide (GSSG) concentrations . In vitro isometric contractile properties were also determined, incl uding maximal tetanic tension (P-o) and maximal twitch tension (P-t), in GSSG content and in GSSG-to-GSH ratios. Hyperoxia for > 48 h result ed in significant decreases in P-o and P-t and an increase in GSSG con tent and in GSSG-to-GSH ratios compared with other groups. Those same animals subjected to IRL showed a further decrease in P-o and P-t. The se data suggest that free radical generation may occur in the diaphrag m during a hyperoxia exposure associated with activation of the GSH re dox cycle and impairment of diaphragm function.