RAT DIAPHRAGM CONTRACTILITY AND HISTOPATHOLOGY ARE AFFECTED DIFFERENTLY BY LOW-DOSE TREATMENT WITH METHYLPREDNISOLONE AND DEFLAZACORT

The extent to which treatment with low doses of the nonfluorinated ste roid methylprednisolone affects diaphragm contractility and morphology is unknown, In the present study, we compared the effects of equipote nt doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism, Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg . kg(-1) or deflazacort 0.5 mg . kg(-1) i.m. Contractile properties and histopath ology were measured after a 6 week treatment period, During treatment, body weight increased in control and methylprednisolone-treated anima ls, but decreased by 4.2+/-1.1% (mean+/-SD) in the deflazacort group, Similarly, diaphragm mass in the deflazacort group was decreased compa red to control and methylprednisolone groups, Twitch tension and twitc h characteristics of isolated diaphragm bundles were similar in the th ree groups, Maximal tetanic tension was decreased in the deflazacort g roup, The force-frequency curve of the deflazacort bundles shifted dow nwards compared to control, Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals, Microscopic examination revealed no gross abnormalities in the three g roups, Histochemical analysis after staining for myosin adenosine trip hosphatase (ATP-ase) showed that in the deflazacort group cross-sectio nal area of type I, IIa and IIb fibres were decreased, We conclude tha t low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimen sions, while deflazacort at an equipotent dose induced generalized fib re atrophy and changes in diaphragm contractility.