Effect of high- and low-dose dexamethasone on regeneration of minced skeletal muscle autografts in rats.

Minced skeletal muscle autografts were carried out in 96 male Sprague-Dawley rats weighing 150 to 175 g. Starting the day of surgery, dexamethasone (DEX) was administered parenterally, 3 X/day, at one of the following doses: 0, 0.001, 0.01, 0.1, or 1.0 mg/kg. Separate groups received each dosage for either 7 or 21 days (N = 8 to 16 per group). On day 22, rats were killed and the immature grafts were excised and weighed. The total number of muscle cells was counted on transverse sections. Collagen, dry matter content, and total and noncollagen protein were measured. The wet weights and the total number of muscle cells for 1.0 or 0.1 mg/kg DEX grafts were less than most other groups, after treatment of either 7 or 21 days. In contrast, 0.001 mg/kg DEX for 21 days was associated with increased cell counts. For either treatment duration, collagen content was higher for 0.001 mg/kg DEX. After 21 days DEX, 0.1 and 0.01 mg/kg groups also had more collagen compared with controls. (The 1.0 mg/kg DEX grafts were not assayed for collagen due to insufficient tissue regeneration). In a subsequent trial, rats received 0.001 mg/kg DEX (N = 14) or vehicle control (N = 11) for 21 days. On day 60, the rats were killed and the grafts, now near maturity, were again analyzed for total myofiber number and collagen content, neither of which was significantly different from controls. In summary, DEX in pharmacologic doses was associated with inhibition of muscle graft regeneration if administered for 7 or 21 days. There was evidence that DEX at 100 to 1000 X lower concentrations caused transient increases in the number of proliferating muscle cells and the collagen concentration.