EFFECTS OF LONG-TERM LOW-DOSE METHYLPREDNISOLONE ON RAT DIAPHRAGM FUNCTION AND STRUCTURE

In animal studies, high dosages of corticosteroids cause changes in di aphragm structure and function. The present study was designed to inve stigate the effects of long-term low-dose methylprednisolone (MP) admi nistration on rat diaphragm contractile properties and morphology. Thi rty adult rats were treated with saline or MP (0.2 mg/kg/day SC) durin g 6 months. Contractile properties of isolated diaphragm strips, immun ohistochemical characteristics analyzed by means of antibodies reactiv e with myosin heavy chain isoforms, and enzyme activities were determi ned in the diaphragm muscle. MP significantly reduced diaphragm force generation by similar to 15% over a wide range of stimulation frequenc ies. The number of type Ilb fibers was reduced by MP. There was a mild but significant decrease in type I and IIa fiber cross-sectional area (CSA), whereas type IIx and IIb CSA did not change. These changes res ulted in a reduction in the relative contribution of type IIb fibers t o total diaphragm muscle area. Biochemically, MP decreased glycogenoly tic activity, while fatty acid oxidation and oxidative capacity were i ncreased. In conclusion, long-term low-dose MP administration caused a marked impairment in diaphragm function. This is accompanied by chang es in diaphragm muscle morphology and enzyme capacity. (C) 1997 John W iley & Sons, Inc.