ORIGINAL ARTICLES

Indomethacin decreases optic nerve oxygen tension by a mechanism other than cyclo-oxygenase inhibition

M Hove Noergaard^1,2, D Bach Pedersen¹, K Bang³, P Koch Jensen¹, J Folke Kiilgaard¹, E Stefánsson⁴ and M la Cour⁵

¹ Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
² Panum Institute, University of Copenhagen, Copenhagen, Denmark
³ Merck Sharp & Dohme, Glostrup, Denmark
⁴ University of Iceland, Reykjavik, Iceland
⁵ Department of Ophthalmology, Glostrup Sygehus, Glostrup, Denmark

Correspondence to:
M Hove Noergaard, Department of Ophthalmology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark; hovemichael{at}yahoo.com

Aims: We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO₂), as indomethacin previously has demonstrated a strong decreasing effect on ONPO₂. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect of dorzolamide on ONPO₂.

Methods: ONPO₂ was measured 0.5 mm above the optic disc in 23 domestic pigs (26–36 kg) with a polarographic oxygen-sensitive electrode. One of the following NSAIDs was administered intravenously as increasing doses or as one large dose: indomethacin, ibuprofen, diclofenac, ketoprofen, parecyclo-oxygenase-2 inhibitor and lornoxicam. Indomethacin was both tested alone and after preceding administration of the other NSAIDs. Dorzolamide was also tested after preceding administration of NSAIDs different from indomethacin.

Results: Indomethacin decreased ONPO₂ significantly in a dose-dependent manner. None of the other NSAIDs produced any effect on the ONPO₂ (p>>0.05; n = 17). No difference was found between the effect of indomethacin injected alone, and after preceding administration of the other NSAIDs. Intravenous dorzolamide (500 mg) increased ONPO₂ by 32 (7)% (n = 7; p<0.001) after preceding administration of several NSAIDs different from indomethacin.

Conclusions: Indomethacin decreased ONPO₂, while the other NSAIDs showed no effect on ONPO₂, and they did not affect the effect of indomethacin. The hypoxic effect of indomethacin must be due to another mechanism than cyclo-oxygenase inhibition. The effect of dorzolamide on ONPO₂ is not related to prostaglandin production.

Funding: Supported by University of Copenhagen and Øjenforeningen—Værn om Synet, Denmark.

Competing interests: None.

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