Glucocorticoid-induced alterations in the rate of diaphragmatic fatigue

These experiments tested the hypothesis that in vitro dliaphragmatic fatigu e resistance is enhanced in animals treated with glucocorticoids. Female Sp rague-Dawley rats (4 months old) were randomly assigned to a control (N=12) or glucocorticoid treatment group (N=12). Treatment animals were injected daily for 8 days with prednisolone (5 mg kg(-1)); control animals were inje cted with the same volume of the vehicle. Twenty-four hours after the last injection, the following in vitro diaphragmatic contractile properties were examined in costal diaphragm strips: maximal twitch (P-t) half time to pea k tension (1/2 TPT), half relaxation time (1/2 RT), force-frequency relatio nship, and the rate of fatigue development. Diaphragmatic fatigue was asses sed by monitoring the decrease in force production (measured as percent of initial force) over a 60-min contractile period. The in vitro fatigue proto col incorporated a supramaximal stimulus delivered at 30 Hz every 2 s with a train duration of 250 ms (duty cycle 12.5%). Citrate synthase (CS), super oxide dismutase (SOD), and water content of the costal diaphragm were also determined. Glucocorticoid administration induced an 18.9% (P < 0.05) decre ase in animal body weight when compared to the control. Similar weight loss es also occurred in the diaphragm with a decrease (P < 0.05) in mass of 16. 5% compared to the control. Furthermore, prednisolone treatment resulted in a significant reduction in the cross-sectional area (CSA) of type IIb fibr es with no change in the CSA area of type I and IIa fibres. 1/2 TPT and 1/2 RT were significantly prolonged (P < 0.05) in the glucocorticoid treated r ats whereas the force-frequency curve was unaltered (P > 0.05). Fatigue res istance was greater in the glucocorticoid group (P < 0.05); the relative fo rce production differed between groups at the end of 1 min of contractions and remained different throughout the 60-min fatigue protocol. Citrate synt hase, SOD, and water content were not different between groups. These exper iments support the hypothesis that costal diaphragm strips of glucocorticoi d-treated rats possess a greater resistance to fatigue. We postulate that t his fatigue resistance is due to glucocorticoid-induced changes muscle fibr e type composition. (C) 2000 Academic Press.