Effect of indomethacin on the hypercapnia-associated vasodilation of the optic nerve head vessels: an experimental study in miniature pigs

Abstract

Purpose: To evaluate whether prostaglandins are mediators of the hypercapnia-associated vasodilation of the optic nerve head vessels.

Methods: We measured the PO(2) at intervascular areas of the optic disc in 9 anaesthetized miniature pigs using oxygen-sensitive microelectrodes placed at <50 mum from the optic disc. PO(2) was measured continuously under normoxia, hyperoxia (breathing of 100% O(2)), carbogen breathing (95% O(2), 5% CO(2)), and hypercapnia (40% increase in inhaled CO(2)). Similar measurements under these conditions were also done after intravenous administration of the prostaglandin inhibitor indomethacin.

Results: Before the injection of indomethacin, we observed a slight increase in the optic disc PO(2) during hypercapnia (DeltaPO(2) = 2.0 +/- 1.7 mm Hg; p < 0.001; n = 18) or hyperoxia (DeltaPO(2) = 3.4 +/- 1.6 mm Hg; p < 0.001; n = 23), but a much more important increase during carbogen breathing (DeltaPO(2) = 12.0 +/- 5.1 mm Hg; p < 0.001; n = 23). After the injection of indomethacin, the increase in the optic disc PO(2) was similar during hyperoxia (DeltaPO(2) = 5.6 +/- 2.2 mm Hg; p < 0.001; n = 9) or carbogen breathing (DeltaPO(2) = 5.8 +/- 3.2 mm Hg; p < 0.001; n = 9), while in hypercapnia the variation of the optic disc PO(2) was minimal (DeltaPO(2) = 0.5 +/- 1.9 mm Hg; p > 0.1; n = 6).

Conclusions: Indomethacin inhibits the vasodilatory effect of increased systemic PaCO(2) on the optic nerve head vessels, leading to a similar moderate increase in the optic disc PO(2) during carbogen breathing as in hyperoxia. Indomethacin also inhibits the increase in the optic disc PO(2) seen during hypercapnia. Those results indicate that prostaglandins are mediators of the hypercapnia-associated vasodilation of the optic nerve head vessels.