EFFECT OF CORTICOSTEROIDS ON DIAPHRAGM FUNCTION AND BIOCHEMISTRY IN THE RABBIT

The effects of corticosteroid administration for 2 weeks on diaphragm histology, biochemistry, and function were assessed in the rabbit at rest and during inspiratory loading to respiratory failure, and compared to the extensor digitorum longus and untreated control animals. There were marked pathologic changes in the diaphragm after corticosteroid administration and significant alterations in diaphragm glycogen level (118.7 ± 2.8 versus 56.2 ± 1.0 mmol/kg wet weight, p < 0.01) and lactate levels (5.3 ± 0.3 versus 3.5 ± 0.4 mmol/kg wet weight, p < 0.01) with only minimal changes in the skeletal muscle. Although respiratory muscle endurance in the control group increased from 142 ± 17 min at baseline to 155 ± 20 at Week 1 and 183 ± 13 at Week 2 (p < 0.05), it fell progressively from 135 ± 19 min at baseline to 99 ± 5 at Week 1 and 88 ± 9 at Week 2 (p < 0.01) in the corticosteroid-treated animals. On the other hand, there was no significant change in resting Pdl(max) after corticosteroid administration. In addition, there was no significant change in Pdl(max), Pdi/Edi ratio, or glycogen level at the point of respiratory failure, but diaphragm lactate levels were increased (8.5 ± 0.8 versus 5.3 ± 0.3, p < 0.05). When variable degrees of diaphragm dysfunction were induced by phrenic nerve pacing and/or thoracoabdominal binding, the degree of biochemical change associated with diaphragm dysfunction was significantly greater in corticosteroid-treated animals. We conclude that corticosteroid administration in the rabbit alters diaphragm histopathology and biochemistry as well as respiratory muscle endurance, but not strength. The reduction in endurance is not associated with the development of diaphragm fatigue or glycogen depletion, but may be related to excessive lactate accumulation or an altered relationship between biochemical changes and the degree of diaphragm dysfunction.