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Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic anhydrase inhibition and carbon dioxide breathing

D B Pedersen^1,2, T Eysteinsson³, E Stefánsson³, J F Kiilgaard^1,2, M la Cour¹, K Bang⁴ and P K Jensen¹

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

Correspondence to:
Correspondence to:
D B Pedersen MD
Department of Ophthalmology, 2061, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark; daniella{at}dadlnet.dk

Background/aims: Prostaglandins are important in blood flow regulation. Carbon dioxide (CO₂) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension (ONPO₂), the authors investigated how indomethacin affects ONPO₂ and the ONPO₂ increases caused by CO₂ breathing and carbonic anhydrase inhibition in the pig.

Methods: Optic nerve oxygen tension was measured in 11 pigs with a polarographic oxygen electrode. The tip of the electrode was placed 0.5 mm above the optic disc. The effects of indomethacin, CO₂ breathing (3%) before and after indomethacin treatment, and carbonic anhydrase inhibition with or without indomethacin treatment were investigated.

Results: Administration of 300 mg indomethacin decreased optic nerve oxygen tension significantly. Carbonic anhydrase inhibition and CO₂ breathing increased ONPO₂ significantly. After indomethacin had been given, the rise in ONPO₂ caused by CO₂ breathing and carbonic anhydrase inhibition was significantly reduced.

Conclusion: Systemic administration of indomethacin decreases the optic nerve oxygen tension; this is probably the result of decreased blood flow through vasoconstriction of vessels in the optic nerve. Additionally, indomethacin diminishes the ONPO₂ increasing effect of CO₂ breathing and carbonic anhydrase inhibition, thus affecting the reactivity of vessels in the optic nerve.

Abbreviations: aPCO₂, arterial PCO₂; apH, arterial pH; aPO₂, arterial PO₂; CAIs, carbonic anhydrase inhibitors; HR, heart rate; MAP, mean arterial pressure; NO, nitric oxide; ONPO₂, optic nerve oxygen tension

Keywords: indomethacin; optic nerve; oxygen tension; carbonic anhydrase inhibition; carbon dioxide breathing

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• Weigert, G., Berisha, F., Resch, H., Karl, K., Schmetterer, L., Garhofer, G. (2008). Effect of Unspecific Inhibition of Cyclooxygenase by Indomethacin on Retinal and Choroidal Blood Flow. IOVS 49: 1065-1070 [Abstract] [Full Text]  
• Noergaard, M H., Pedersen, D B., Bang, K, Jensen, P K., Kiilgaard, J F., Stefansson, E, la Cour, M (2008). Indomethacin decreases optic nerve oxygen tension by a mechanism other than cyclo-oxygenase inhibition. Br. J. Ophthalmol. 92: 126-130 [Abstract] [Full Text]