Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism

An important adverse effect of corticosteroid treatment is respiratory musc le weakness with diaphragm muscle wasting, but little is known about the un derlying pathophysiological processes involved. In order to differentiate b etween the effects of nutrition depletion and corticosteroids on diaphragm muscle metabolism, a study was performed to investigate the effects of tria mcinolone (TR) for 2 weeks and of chronic undernutrition in a pair-weight ( PW) group on the structure and energy metabolism of the diaphragm in male W istar rats compared with a free-fed (FF) group. Diaphragm mass was reduced in TR and PW rats to a similar degree, but the extent of type-IIx/b atrophy was more pronounced in TR rats than in PW rats. No myopathic features were observed after either treatment. ATP in absolute terms as well as the ATP/ ADP ratio, total adenine nucleotides, the phosphocreatine (PCr) level and t he ratio between PCr and creatine (PCr/Cr) were decreased in the diaphragm of both TR and PW rats. In contrast to the PW group, the total Cr pool was reduced and pyruvate and lactate levels were elevated in the diaphragm of t he TR group compared with the FF group. In conclusion, the results of this study indicate that severe undernutrition causes a decrease in muscle energ y status resulting in a new metabolic equilibrium, while chronic low-dose T R treatment (0.25 mg/kg per day i.m.) causes a decrease in muscle energy st atus together with a mismatch between glycolysis and oxidative metabolism.