Effect of carbogen breathing and acetazolamide on optic disc PO2.

PURPOSE: Acetazolamide was previously shown to increase optic disc partial pressure of oxygen (PO(2)). The study was conducted to evaluate optic disc PO(2) variations during normoxia, hyperoxia (100% O(2)), and carbogen breathing (95% O(2), 5% CO(2)), before and after intravenous administration of acetazolamide. METHODS: PO(2) measurements were obtained at intervascular areas of the optic disc in nine anesthetized minipigs using oxygen-sensitive microelectrodes (10-microm tip diameter) placed at <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia, or carbogen breathing. Oxygen measurements were repeated under these conditions after intravenous injection of acetazolamide (500-mg bolus). RESULTS: In hyperoxia, optic disc PO(2) increased moderately (DeltaPO(2) = 4.81 +/- 1.16 mm Hg (mean +/- SD; 24%; P < 0.001) after a much larger increase in systemic PaO(2). Carbogen breathing induced a significant increase in both systemic PaO(2) and PaCO(2), which resulted in a large increase in optic disc PO(2) (DeltaPO(2) = 13.17 +/- 2.18 mm Hg; 67%; P < 0.001). Acetazolamide induced a slow and progressive increase in both systemic PaCO(2) and optic disc PO(2) (30 minutes DeltaPO(2) = 4.24 +/- 2.45 mm Hg; 24%; P < 0.04). However, it was when carbogen was simultaneously administered that optic disc PO(2) increased most substantially (DeltaPO(2) = 18.91 +/- 5.23 mm Hg; 90%; P < 0.002). CONCLUSIONS: Carbogen breathing increases optic disc Po(2) significantly in minipigs, more than hyperoxia. The association of acetazolamide injection with carbogen breathing could induce an additional increase in optic disc PO(2) through the effect of higher systemic PaCO(2).

Light-induced retinal vascular damage by Pd-porphyrin luminescent oxygen probes.

PURPOSE: The phosphorescence lifetime of certain metalloporphyrins dissolved in a physiological medium provides an optical signature for local oxygen concentration (pO(2)). This effect is used for measuring physiological pO(2) levels in various tissues. However, the phosphorescence quenching of certain metalloporphyrin triplet states by oxygen also creates singlet oxygen, which is highly reactive and capable of inducing tissue damage. In the current study, the Pd-meso-tetra(4-carboxyphenyl) porphyrin dye (PdTCPP) was simultaneously used as an oxygen sensor and a photosensitizer. Phototoxicity was assessed in the eye fundus and correlated with tissue oxygenation, drug-light dose, and severity of tissue damage. METHODS: The kinetics of photochemical oxygen depletion during PdTCPP excitation was measured in vivo on the optic disc of piglets by phosphorescence lifetime imaging. Blood-retinal barrier breakdown and tissue damage were assessed by confocal and electron microscopy. RESULTS: For a retinal irradiance of 5 mW/cm(2) at 532 nm and an injected PdTCPP dose of 20 mg/kg, the mean phosphorescence lifetime measured at the optic disc increased from 100 to 600 micros within 8 minutes of continuous illumination. This corresponds to a decrease of pO(2) from 25 to 0 mm Hg, induced by a light dose of only 2.4 J/cm(2). An exposure time of 6 minutes (1.8 J/cm(2)) generated an increase in phosphorescence lifetime from 100 to 400 micros, corresponding to a decrease in pO(2) from 25 to 4 mm Hg. This caused edema in all retinal layers, whereas irradiation of 2 minutes (0.6 J/cm(2)) damaged blood vessels and induced edema in the inner nuclear layer only. Heavy redistribution of occludin occurred after a 30-minute exposure time (9 J/cm(2)). CONCLUSIONS: PdTCPP is potentially phototoxic under certain experimental conditions and can induce damage in peripapillary retina and optic nerve head after light exposure. The severity of tissue damage correlates with the phosphorescence measurements.

Experimental retinal vein occlusion: effect of acetazolamide and carbogen (95% O2/5% CO2) on preretinal PO2.

PURPOSE: To evaluate the variations of preretinal oxygen partial pressure (Po(2)) in normal and in ischemic postexperimental branch retinal vein occlusion (BRVO) areas, during normoxia, hyperoxia (100% O(2)), and carbogen (95% O(2), 5% CO(2)) breathing before and after intravenous injection of acetazolamide. METHODS: Preretinal Po(2) measurements were obtained in intervascular retinal areas, distant from the retinal vessels of 13 anesthetized mini-pigs with oxygen-sensitive microelectrodes (10 microm tip diameter) introduced through the vitreous cavity by a micromanipulator. The microelectrode tip was placed <50 microm from the vitreoretinal interface in the preretinal vitreous. Po(2) was measured continuously for 10 minutes under systemic normoxia, hyperoxia, and carbogen breathing. A BRVO was induced with an argon green laser, and oxygen measurements were repeated under normoxia, hyperoxia, and carbogen breathing, before and after intravenous injection of acetazolamide (500 mg bolus). RESULTS: In hyperoxia, a moderate nonsignificant preretinal Po(2) increase in both normal (DeltaPo(2) = 2.20 +/- 4.16 mm Hg; n = 25) and ischemic retinas (DeltaPo(2) = 4.30 +/- 3.57 mm Hg; n = 16) was measured in spite of a substantial increase in systemic Pao(2). Carbogen breathing induced a significant increase in systemic Paco(2) and a higher systemic Pao(2) than hyperoxia. Furthermore, it significantly increased the preretinal Po(2) in normal areas (DeltaPo(2) = 19.37 +/- 16.41 mm Hg; n = 26), and in ischemic areas (DeltaPo(2) = 14.94 +/- 8.53 mm Hg; n = 14). Intravenous acetazolamide did not affect the preretinal Po(2). Acetazolamide induced an increase of the preretinal Po(2) to a greater extent when it was associated with carbogen breathing (DeltaPo(2) = 15.15 +/- 9.15 mm Hg; n = 7) than when it was combined with hyperoxia (DeltaPo(2) = 6.96 +/- 4.49 mm Hg; n = 7). CONCLUSIONS: Carbogen breathing significantly increased preretinal Po(2) in normal and in ischemic postexperimental BRVO areas of mini-pigs. The concomitant use of acetazolamide injection and carbogen breathing or hyperoxia could restore an appropriate oxygenation of BRVO areas.