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D.B. Pedersen, M.H. Noergaard, E. Stefánsson, P.K. Jensen, T. Eysteinsson, K. Bang, M.l. Cour; Dorzolamide Increases Optic Nerve Oxygen Tension Independent of Cyclooxygenase Inhibition . Invest. Ophthalmol. Vis. Sci. 2006;47(13):489.
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© ARVO (1962-2015); The Authors (2016-present)
It has been hypothesized that prostaglandins and cyclooxygenase play a role in the regulation of retinal and optic nerve blood flow and oxygenation. We have previously reported that indomethacin as the only Non–Steroidal Anti–Inflammatory Drug (NSAID) reduces oxygen tension in the pig optic nerve head. Also indomethacin suppresses the effect of CO2 and carbonic anhydrase inhibitors (CAIs), which otherwise elevate the optic nerve oxygen tension (ONPO2). We investigated whether other cyclooxygenase inhibitors affected the ONPO2 increasing effect of CAIs.
Optic nerve oxygen tension was measured in 6 pigs (Danish landrace, approx. 30 kg) with a polarographic oxygen electrode (model 768–20R, Diamond General Development Corporation, Ann Arbor, MI, USA). Treatment of the pigs followed the ARVO resolution for the use of animals in ophthalmic and vision research. The tip of the electrode was placed in the vitreous humour 0.5 mm above the optic disc. Different non–steroidal anti–inflammatory drugs (NSAIDs) and cyclooxygenase inhibitors (100 mg ketoprofen,75 mg diclofenac, 1000 mg ibuprofen, 8 mg lornoxicam and 40 mg parecoxib) were injected intravenously. 30 minutes after 500 mg dorzolamide was injected. ONPO2, arterial blood pressure, heart rate and arterial blood gasses were recorded continuously.
Administration of the various NSAIDs did not affect ONPO2 or the systemic values significantly. 500 mg dorzolamide increased ONPO2 significantly by 28.9 ± 7% (p<0.001) which is similar to the effect of dorzolamide without preceding administration of NSAIDs.
The ONPO2 increasing effect of dorzolamide is not affected by cyclo–oxygenase inhibition. Further investigations on the mechanism of action of carbonic anhydrase inhibition should be performed.
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