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Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic anhydrase inhibition and carbon dioxide breathing
  1. D B Pedersen1,2,
  2. T Eysteinsson3,
  3. E Stefánsson3,
  4. J F Kiilgaard1,2,
  5. M la Cour1,
  6. K Bang4,
  7. P K Jensen1
  1. 1Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
  2. 2University of Copenhagen, Denmark
  3. 3Department of Ophthalmology, University of Iceland, Reykjavik, Iceland
  4. 4Merck, Sharp & Dohme, Glostrup, Denmark
  1. Correspondence to: D B Pedersen MD Department of Ophthalmology, 2061, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark; danielladadlnet.dk

Abstract

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.

  • 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
  • indomethacin
  • optic nerve
  • oxygen tension
  • carbonic anhydrase inhibition
  • carbon dioxide breathing
  • 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
  • indomethacin
  • optic nerve
  • oxygen tension
  • carbonic anhydrase inhibition
  • carbon dioxide breathing

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Footnotes

  • Supported by University of Copenhagen, Værn om Synet, Denmark, MSD Inc, Denmark, University of Iceland Research Fund, and Helga Jónsdóttir and Sigurlioi Kristjánsson memorial Fund, Iceland.