Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently.

Abstract

Diaphragm atrophy and weakness occur after administration of massive doses of corticosteroids for short periods. In the present study the effects of prolonged administration of moderate doses of fluorinated and nonfluorinated steroids were investigated on contractile properties and histopathology of rat diaphragm. 60 rats received saline, 1.0 mg/kg triamcinolone, or 1.25 or 5 mg/kg i.m. prednisolone daily for 4 wk. Respiratory and peripheral muscle mass increased similarly in control and both prednisolone groups, whereas triamcinolone caused severe muscle wasting. Maximal tetanic tension averaged 2.23±0.54 kg/cm2 (SD) in the control group. An increased number of diaphragmatic bundles in the 5-mg/kg prednisolone group generated maximal tetanic tensions < 2.0 kg/cm2 (P < 0.05). In addition, fatigability during the force-frequency protocol was most pronounced in this group (P < 0.05). In contrast, triamcinolone caused a prolonged half-relaxation time and a leftward shift of the force-frequency curve (P < 0.05). Histological examination of the diaphragm showed a normal pattern in the control and 1.25-mg/kg prednisolone group. Myogenic changes, however, were found in the 5-mg/kg prednisolone group and, more pronounced, in the triamcinolone group. Selective type Ilb fiber atrophy was found in the latter group, but not in the prednisolone groups. In conclusion, triamcinolone induced type IIb fiber atrophy, resulting in reduced respiratory muscle strength and a leftward shift of the forcefrequency curve. In contrast, 5 mg/kg prednisolone caused alterations in diaphragmatic contractile properties and histological changes without fiber atrophy. (J. Clin. Invest. 1993.

Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in glucocorticoid-treated rats

“…Glucocorticoid-induced myopathy is characterized by a decrease in the size of muscle fibers (13). In the present study, glucocorticoid treatment caused a 31% decrease in mean muscle fiber CSA of TA muscle compared to controls.…”

“…Second, the present study did not measure muscle fiber CSA based on muscle fiber phenotype, as TA muscle in rats is almost exclusively composed of type II fibers. Although glucocorticoids are known to cause muscle atrophy of fast-twitch (type II) muscle fibers (13), the effects of glucocorticoids on muscle fiber phenotypes in other muscles should be evaluated in future studies.…”

“…Among several stimulatory conditions ranged from 20 to 100 Hz, our preliminary studies identified stimulation at 40 Hz as the best condition to show differences in muscle strength and fatigue between controls and glucocorticoid-treated rats (34). This is probably because glucocorticoid-induced myopathy is characterized by atrophy of type II muscle fibers (13). We have thus determined 40-Hz stimulation represents the optimal condition for drug intervention in glucocorticoid-treated rats (34).…”

“…Muscle weakness is determined by not only decreases in muscle strength, but also muscle fatigue. Contractile tension assessed by electrical stimulation can be used to evaluate skeletal muscle strength and fatigue in animal models (3,13,37,43). Using this method, the present study investigated whether alfacalcidol [1α(OH)D 3 ], an active vitamin D analog, exerts favorable effects on muscle strength and fatigue in glucocorticoid-treated rats.…”

Muscle weakness is related to utilization of health care resources in COPD patients

“…There is no doubt that the relationship between steroid treatment and muscle weakness may be causal. Indeed, numerous animal studies have demonstrated a causal relationship between steroid treatment and muscle weakness [34,36]. Following this hypothesis, enhanced complaints would lead both to hospital admission and steroid treatment, with consequent muscle weakness.…”