dorzolamide and Hypercapnia

To determine by a pilot study whether standard treatment with the topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual function under normal breathing conditions, during carbon dioxide inhalation, or during hyperventilation, and to establish criteria for future larger-scale studies.. We enrolled 12 normal subjects into this randomized double-masked placebo-controlled crossover study. Each subject was treated with either dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout period, the alternative topical agent was used under identical testing conditions. On day 2 of each treatment phase, contrast sensitivities to sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4, mean deviation values from full-threshold 10-2 visual fields were obtained. Three sets of each visual function test were obtained before each treatment phase, and in sequence on each testing day, during normal breathing (baseline), inhalation of carbon dioxide-enriched air, and hyperventilation while intraocular pressure was monitored.. Contrast sensitivity at 4 cpd decreased significantly (P < .01) during carbon dioxide supplementation with placebo but showed no significant change with dorzolamide. The decrease in contrast sensitivity accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry mean deviation values under each treatment condition and was statistically significant (P < .05) at baseline.. Dorzolamide appears to enhance contrast sensitivity in normal subjects during physiologic hypercapnia and hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions, dorzolamide therapy increases perimetric light sensitivity.

Topics: Adult; Carbonic Anhydrase Inhibitors; Contrast Sensitivity; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypercapnia; Hypocapnia; Intraocular Pressure; Male; Ophthalmic Solutions; Pilot Projects; Sulfonamides; Thiophenes; Visual Field Tests; Visual Fields

Purpose. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. Methods. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO(2) (PetCO(2)) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. Results. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P < 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P = 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P

Topics: Administration, Topical; Aged; Arterioles; Blood Flow Velocity; Carbonic Anhydrase Inhibitors; Disease Progression; Glaucoma, Open-Angle; Humans; Hypercapnia; Intraocular Pressure; Laser-Doppler Flowmetry; Middle Aged; Optic Disk; Regional Blood Flow; Retinal Artery; Sulfonamides; Thiophenes

Carbonic anhydrase inhibitors reduce intraocular pressure, which may protect the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to dilate the blood vessels in the retina and the optic nerve head. The purpose of the present study was to investigate whether CO(2), H(+), or factors other than carbonic anhydrase inhibition are involved in this vasodilating effect.. Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric force measurements. After precontraction with the prostaglandin analogue U46619, concentration-response experiments were performed with acetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were performed at normal pH and during acidosis, during normocapnia and hypercapnia, as well as in the nominal absence of CO(2) and HCO(3)(-).. The maximum relaxation was significantly lower and the EC(50) significantly higher during normal pH compared with acidosis (P = 0.002 and P < 0.0001, respectively), but neither the maximum relaxation nor EC(50) was changed by hypercapnia (P = 0.054 and P = 0.57, respectively). The findings confirmed that carbonic anhydrase-induced vasodilation depends on the perivascular retinal tissue and that dorzolamide produces significantly more pronounced relaxation than does acetazolamide. EC(50) of carbonic anhydrase inhibitor-induced vasorelaxation and the maximum relaxation of dorzolamide were unchanged in the nominal absence of CO(2) and HCO(3)(-) (P = 0.65 and P < 0.0001, respectively).. The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal arterioles depends on the perivascular retinal tissue and acidosis, but not on hypercapnia. The effect involves mechanisms other than carbonic anhydrase inhibition.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetazolamide; Acidosis; Animals; Arterioles; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Dose-Response Relationship, Drug; Hydrogen-Ion Concentration; Hypercapnia; Muscle, Smooth, Vascular; Myography; Nifedipine; Retinal Artery; Sulfonamides; Swine; Thiophenes; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents