Effects of topical adrenergic agents on tissue circulation in rabbit and human optic nerve head evaluated with laser speckle tissue circulation analyzer.
The effects of topical adrenergic agents on the tissue circulation of the optic nerve head (ONH) were studied in animal and human eyes with use of a laser speckle tissue circulation analyzer. Drugs studied were nipradilol, a beta1-2-blocker with weak alpha-blocking and nitroglycerinlike activities; bunazosin, a selective alpha1-blocker; carteolol, a beta1-2-blocker with intrinsic sympathomimetic activity; and betaxolol, a selective beta1-blocker. In the animal experiment, one eye each of nine albino rabbits received 0.25% nipradilol (N = 9) twice daily for 15 days or 0.01% bunazosin (N = 10) twice daily for 20 days; the fellow eye received the vehicle of each drug in a randomized masked design. Normalized blur (NB) in an area of ONH free of visible surface vessels, a quantitative index of peripheral blood velocity in ONH, was measured under general anesthesia before treatment and 2 hours after the last instillation on the 15th or 20th day. At 15 days, intraocular pressure and NB in the nipradilol-treated eyes decreased by 4.3 mm Hg (P < 0.01) and increased by 15.9% (P < 0.01), respectively, while those in the vehicle-treated eyes showed little change. At 20 days NB in both bunazosin- and vehicle-treated eyes showed little change, while intraocular pressure decreased only in the bunazosin-treated eyes (P < 0.01). In the human volunteer experiment NB was averaged over five pulses (mean NB) in both eyes before and 1.5, 3.0 and 4.5 hours after a 30 microL instillation of the vehicle of carteolol or betaxolol to serve as a control. Intraocular pressure, blood pressure and pulse rate were also measured. One week later a 30 microL drop of 2.0% carteolol (N = 6) or 0.5% betaxolol (N = 10) was instilled in one randomly chosen eye and the vehicle for each drug in the other eye, and those parameters were measured as above in a double-masked manner. In the carteolol experiment, mean NB in both eyes was significantly higher at 3 hours than it was in the control experiment (P < 0.05), while intraocular pressure was significantly lower in both eyes and blood pressure and pulse rate showed little change. In the betaxolol experiment, intraocular pressure at 1.5 hours and blood pressure at 4.5 hours were significantly lower than those in the control experiment (P < 0.05), while mean NB and pulse rate showed little change. In summary, using the laser speckle method we found that topical nipradilol and carteolol increase ONH blood velocity in rabbits and humans, respectively. This finding suggests that some topical beta-blockers used clinically may influence the ONH tissue circulation in patients and that this method may be used in clinical situations to assess the effect of various drugs on ONH circulation.
Tamaki
Y
Y
Eye Clinic, Tokyo Metropolitan Geriatric Hospital, Japan.
Araie
M
M
Tomita
K
K
Tomidokoro
A
A
Nagahara
M
M
D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D015784:Betaxolol / Q000008:administration & dosage / Q000494:pharmacology; D001775:Blood Circulation / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002354:Carteolol / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D018056:Hemorheology / Q000295:instrumentation; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D009883:Ophthalmic Solutions; D009898:Optic Disk / Q000098:blood supply*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011412:Propanolamines; D011799:Quinazolines; D002354:Carteolol; C018176:bunazosin; C036089:nipradilol; D015784:Betaxolol