Effects of Steroids on Diaphragmatic Function in Rats

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Abstract
The present study was undertaken to determine the effects of 8 days of corticosteroid administration on diaphragmatic atrophy and contractile properties. One hundred sixty rats were divided into a pair-fed (PF) group (n = 80)and a steroid-treated (ST) group (n = 80). The treated rats received a single injection of Kenacort 80 retard (0.1 mg/kg intramuscularly). The experimental period was 8 days. Steroid treatment resulted in a 30% decrease in body weight in the ST group when compared with the PF group. Diaphragmatic mass in the ST group decreased in proportion to body weight (30%) as did the weight of the extensor digitorum longus (EDL). The soleus muscle was unaffected. The diaphragmatic atrophy was associated with a significant decrease (p < 0.001) in normalized tetanic force as assessed both in vivo and in vitro. Diaphragmatic strength was determined in vivo by measuring transdiaphragmatic pressure (Pdi) during bilateral electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 100 Hz). The force-frequency relationship was also studied in vitro using direct stimulation of costal diaphragmatic strips. In both preparations, twitch and low-frequency force were unaffected, whereas normalized tetanic force in the ST group was markedly reduced compared with that in the PF group (p < 0.001). Soleus and EDL muscles were also studied in vitro. Although steroid treatment had no effect on the soleus, in the EDL, a slight (11%) decrease in normalized tetanic tension was observed. This was significantly less, however, than the decrease seen in the diaphragm, which amounted to 26% less than that in the PF animals. We conclude that in the rat, 8 days of steroid administration produces diaphragmatic atrophy as severe as that of the fast-twitch hindlimb muscle and that this atrophy is accompanied by a reduction in normalized tetanic force that is significantly greater than that observed in peripheral muscle.