In an experimental rat model of neoplastic
spinal cord compression, the in vivo effect of steroidal and
nonsteroidal anti-inflammatory agents on the water content,
prostaglandin E2 (
PGE2) production, and specific gravity of the compressed cord segments were assessed, as well as the effect on the course of the disease. Paraplegic animals presented a consistent increase in the water content,
PGE2 synthesis, and specific gravity in the compressed cord segments. The effect of treatment given on onset of
paraplegia with either
dexamethasone sodium phosphate (Dex-p; 10 mg/kg twice daily), or free
dexamethasone (F-dex; 8.25 mg/kg twice daily) or
indomethacin (10 mg/kg twice daily), was evaluated after 30 hours of
therapy. Both F-dex and
indomethacin eliminated spinal cord
edema but varied in the rate of inhibitory effect on
PGE2 production (
dexamethasone less than
indomethacin).
Dexamethasone sodium phosphate failed to reduce spinal cord
edema and
PGE2 synthesis, but specific gravity changes were corrected by each of the administered agents. Evaluation of the effect of treatment on the course of the disease required
dose reduction by 50% for Dex-p and F-dex, and to 25% for
indomethacin, to avoid lethal toxicity. Treatment was started on appearance of the first sign of
neurologic dysfunction (Grade 1) and continued to
paraplegia (Grade 5). In the saline-treated rats, the mean time interval between Grades 1 and 5 was 2.7 +/- 0.3 days. Free
dexamethasone, Dex-p, and
indomethacin significantly prolonged this interval by 57%, 54%, and 48% respectively (P less than 0.005). The three agents differed in their ability to control the increases in water content and in
PGE2 production, but proved almost equally effective in the prompt control of the specific gravity changes.(ABSTRACT TRUNCATED AT 250 WORDS)