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Optic Nerve Oxygen Tension is Not Affected by a Metabolic Acidosis

¹ Ophthalmological Department 2061 Rigshospitalet Copenhagen Denmark
² University of Iceland Reykjavijk Iceland
³ Merck Sharp & Dohme Glostrup Denmark

Commercial Relationships:   D.B. Pedersen, Merck, Sharp & Dohme F; T. Eysteinsson, Merck, Sharp @ Dohme F; J.F. Kiilgaard, Merck, Sharp & Dohme F; M. la Cour, Merck, Sharp & Dohme F; E. Stefánsson, Merck, Sharp & Dohme F; K. Bang, Merck, Sharp & Dohme E; J. Dollerup, Merck, Sharp & Dohme E; P.K. Jensen, Merck, Sharp & Dohme F.
Grant Identification: University of Copenhagen and MSD

Abstract

Purpose:The carbonic anhydrase inhibitors dorzolamide and acetazolamide increase the oxygen tension over the pig optic nerve (ONPO₂). Dorzolamide lowers the optic nerve pH (ONpH) in pigs, as does NH₄Cl. In order to test the hypothesis that the ONpH change induce the ONPO₂ increase, we studied whether a NH₄Cl induced metabolic acidosis leads to an increase in ONPO₂.
Methods:500 mg dorzolamide HCl (Trusopt, MSD Inc.) and 50 ml 10% NH₄Cl (Bie & Berntsen) was injected intravenously in respectively 7 and 4 pigs (Danish landrace, approx. 30 kg). The oxygen tension over the optic nerve (ONPO₂) was measured continuously with a polarographic oxygen electrode mounted with an internal Ag/AgCl reference electrode inside a 20-gauge needle (model 768-20R, Diamond General Development Corporation, Ann Arbor, MI, USA). The tip of the electrode was placed in the vitreous humour 0.5 mm above the optic disc in anaesthetized pigs. The pigs were anaesthetized during the course of the experiments; their treatment was supervised by a veterinarian nurse and followed the ARVO resolution for the use of animals in ophthalmic and vision research.
Results:Baseline ONPO2 (mean ± SEM) was 20.7 mmHg ± 2.4 mmHg while blood PO2 was 94.8 mmHg ± 6.6 mmHg (n=11). Administration of 500 mg dorzolamide caused an increase in the mean ONPO₂ of 5.8 mmHg ± 1.2 mmHg (p=0.003) after 10 min and 7.7 mmHg ± 1.4 mmHg (p=0.001) after 30 min. Administration of 50 ml 10% NH₄Cl did not significantly increase ONPO₂ at either time point. Mean arterial pressure, heart rate and PO₂ in blood were constant during the experiment.
Conclusion:A lowering of optic nerve pH per se caused by a metabolic acidosis does not cause an increase in the optic nerve oxygen tension. The elevated ONPO₂ seen with carbonic anhydrase inhibition is probably not due to pH changes in the blood and optic nerve. Other mechanisms, such as CO₂ accumulation or a direct vascular effect should be considered.

Keywords: 498 optic disc • 514 pharmacology • 512 PH regulation/protons

© 2002, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.