Effects of long-term low-dose methylprednisolone on rat diaphragm function and structure

Abstract

In animal studies, high dosages of corticosteroids cause changes in diaphragm structure and function. The present study was designed to investigate the effects of long-term low-dose methylprednisolone (MP) administration on rat diaphragm contractile properties and morphology. Thirty adult rats were treated with saline or MP (0.2 mg/kg/day s.c.) during 6 months. Contractile properties of isolated diaphragm strips, immunohistochemical characteristics analyzed by means of antibodies reactive with myosin heavy chain isoforms, and enzyme activities were determined in the diaphragm muscle. MP significantly reduced diaphragm force generation by -15% over a wide range of stimulation frequencies. The number of type IIb 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 resulted in a reduction in the relative contribution of type IIb fibers to total diaphragm muscle area. Biochemically, MP decreased glycogenolytic activity, while fatty acid oxidation and oxidative capacity were increased. In conclusion, long-term low-dose MP administration caused a marked impairment in diaphragm function. This is accompanied by changes in diaphragm muscle morphology and enzyme capacity.