Human retinal hemodynamics following administration of 5-isosorbide mononitrate.
OBJECTIVE
The purpose of this randomized double-masked cross-over study was to determine the effects of 20 mg of 5-isosorbide mononitrate (ISMO) on the retinal hemodynamics of young healthy subjects.


METHODS
Monochromatic fundus photography and bidirectional laser Doppler velocimetry (BLDV) were used to determine vascular diameters (D), and blood velocity (V(max)) and flow (Q) in retinal veins, respectively. The diameter of the vein [D((vein))] at the same location where BLDV measurements were made, and the diameter of a neighboring artery [D((art) )], were determined from the fundus photographs. Measurements were carried out one and three hours after ISMO dosing, on twelve and six subjects, respectively. Mean blood pressure (BP(m)) and intraocular pressure (IOP) were also monitored, and ocular perfusion pressure (PP) was calculated. Results are expressed in percentage changes (+/- the standard error of the mean).


RESULTS
On average, we observed a moderate increase of Q one hour after ISMO dosing (+8.2 +/- 5.4%), but not after placebo (+2.7 +/- 1.6%). This effect of ISMO, which displayed remarkable interindividual variability (95% confidence interval: -3.9%, +20.4%), did not attain statistical significance. D((vein)) and D((art)) were not appreciably affected. No effect was observed three hours after either ISMO or placebo dosing. PP was reduced one hour following ISMO administration, mainly as a function of reduced BP(m), although this variation was not statistically significant. IOP did not change appreciably throughout the duration of the study.


CONCLUSIONS
Our findings suggest that, in contrast to the optic nerve head, in which we previously documented consistent and significant increases in blood flow following ISMO administration at both one and three hours, retinal hemodynamics are not equally responsive to a single dose of ISMO at these time points. Marked interindividual variability to the effects of this long-acting nitric oxide donor was documented one hour after administration, but not at three hours. This study further suggests that distinct vascular tissues of the ocular microcirculation respond differently to identical pharmacological challenges.
Iannaccone
A E
AE
Department of Ophthalmology, School of Medicine, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA. iannacca@mail.eye.utmem.edu
DuPont
J
J
Grunwald
J E
JE
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005123:Eye / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate