Investigative ophthalmology & visual science · 1999
Effects of topical beta-blockers on the diameter of the isolated porcine short posterior ciliary artery.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Braakman R, van der Linden P, Sipkema P
Аннотация
PURPOSE: Based on diameter measurements on the short posterior ciliary artery, this study was intended to determine the direct pharmacologic effect of beta-blockers; to determine the differences among a selective beta-blocker betaxolol, a beta-blocker with intrinsic sympathetic activity befunolol, and a nonselective beta-blocker timolol; and to find experimental evidence for the indirect hemodynamic effect of beta-blockers.
METHODS: A segment of isolated porcine short posterior ciliary artery was cannulated at both ends and mounted in a pressurized vessel chamber. Vessel diameter was measured as a function of beta-blocker concentration and as a function of change in transmural pressure.
RESULTS: In the absence of flow, the mean effective doses (ED50) were 0.8 +/- 0.3 mM, 1.0 +/- 0.3 mM, and 11.6 +/- 6.6 mM (SEM) for betaxolol, befunolol, and timolol, respectively. In the presence of flow, vessel diameter increased with an increase of transmural pressure. The mean relative diameter increased 4.2% +/- 1.0% (SEM) at a transmural pressure step from 30 mm Hg to 60 mm Hg. This increase was not significantly dependent on the presence of any of the beta-blockers.
CONCLUSIONS: Only at concentrations far exceeding their expected plasma concentrations, betaxolol, befunolol, and timolol increased the diameter of the isolated porcine short posterior ciliary artery, as a result of their direct pharmacologic effect. Only the difference between the vasodilatory potency of the selective and the nonselective beta-blocker was significant: ED50 of betaxolol was 15 times smaller than ED50 of timolol. There was a positive correlation between the diameter of the isolated porcine short posterior artery (when used as a model for an intraocular artery) and the transmural pressure, which corroborates the indirect hemodynamic effect of beta-blockers. It is speculated that instillation of topical beta-blockers into the conjunctival sac may increase the perfusion of the optic nerve head by an indirect hemodynamic mechanism, but not by a direct pharmacologic mechanism.
METHODS: A segment of isolated porcine short posterior ciliary artery was cannulated at both ends and mounted in a pressurized vessel chamber. Vessel diameter was measured as a function of beta-blocker concentration and as a function of change in transmural pressure.
RESULTS: In the absence of flow, the mean effective doses (ED50) were 0.8 +/- 0.3 mM, 1.0 +/- 0.3 mM, and 11.6 +/- 6.6 mM (SEM) for betaxolol, befunolol, and timolol, respectively. In the presence of flow, vessel diameter increased with an increase of transmural pressure. The mean relative diameter increased 4.2% +/- 1.0% (SEM) at a transmural pressure step from 30 mm Hg to 60 mm Hg. This increase was not significantly dependent on the presence of any of the beta-blockers.
CONCLUSIONS: Only at concentrations far exceeding their expected plasma concentrations, betaxolol, befunolol, and timolol increased the diameter of the isolated porcine short posterior ciliary artery, as a result of their direct pharmacologic effect. Only the difference between the vasodilatory potency of the selective and the nonselective beta-blocker was significant: ED50 of betaxolol was 15 times smaller than ED50 of timolol. There was a positive correlation between the diameter of the isolated porcine short posterior artery (when used as a model for an intraocular artery) and the transmural pressure, which corroborates the indirect hemodynamic effect of beta-blockers. It is speculated that instillation of topical beta-blockers into the conjunctival sac may increase the perfusion of the optic nerve head by an indirect hemodynamic mechanism, but not by a direct pharmacologic mechanism.