Optic Nerve Hypoxia Results From Indomethacin, But Not From Other Anti–Inflammatory Drugs

Abstract

Abstract: : Purpose: Indomethacin lowers optic nerve oxygen tension (ONPO₂) in pigs. We investigated the dose–response relationship of this effect. We also tested whether other non–steroidal anti–inflammatory drugs (NSAIDs), a COX–2 inhibitor or methylprednisolon have a similar effect. Methods: ONPO₂ was measured in the eyes of 16 domestic pigs (26–36 kg) with a polarographic oxygen electrode placed 0.5–1.0 mm above the optic disc. After baseline ONPO₂ was reached, one of the following drugs were injected: indomethacin, ibuprofen , diclofenac, ketoprofen, parecoxib (a selective COX–2 inhibitor), lornoxicam and the corticosteroid methylprednisolon. The drugs were given in increasing dosages or in one large dose. Indomethacin was both tested alone and after previous injection of each of the other drugs. Results: 30 min. after systemic injection of various dosages of indomethacin, ONPO₂ decreased significantly by 35%±10 (3mg), 38%±12 (5mg), 42%±13 (10mg), 50%±15 (20mg), 56%±11 (25mg), 63%±12 (50mg), 73%±17 (100mg), 78%±13 (150mg); n=12, mean±SD, p<0.01 for all levels. None of the other NSAIDs showed any significant change in ONPO₂. No difference was found between the effect of indomethacin injected alone and after previous injection of any of the other drugs. Conclusions: Indomethacin lowered ONPO₂ in a dose dependent fashion. This response was half maximal (EC₅₀) at 0.3 mg/kg. However, both the other tested NSAIDs, a selective COX–2 inhibitor and a corticosteroid showed no effect on ONPO₂. Since all the tested drugs inhibit prostaglandin synthesis, the hypoxic effect of indomethacin must be due to some other mechanism than inhibition of prostaglandin production. Further studies are needed to elucidate this mechanism as well as the possible clinical effect of indomethacin induced optic nerve hypoxia.

Keywords: blood supply • ischemia • pharmacology