Abstract
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