Ocular Physiology, Optic Disk, Regional Blood Flow
Conditions
Keywords
Endothelin-1, L-NG-Monomethyl Arginine, Optic Nerve Head blood flow
Brief summary
Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Previous findings suggest endothelial dysfunction in glaucomatous optic neuropathy, in particular alterations in endothelin- and nitric oxide- system, which both play an important role in local regulation of vascular tone. In the present study, changes in ocular perfusion pressure will be performed during administration of drugs, which may potentially alter the pressure-flow relationship. These drugs include endothelin-1 and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA).
Interventions
bolus 6 mg/kg over 5 minutes followed by a continuous intravenous infusion of 60 µg/kg/min over 12 minutes; twice on 1 study day
DRUGEndothelin-1 (ET-1)
5 ng/kg/min intravenous infusion over 17 minutes; twice on 1 study day
DRUGPhysiologic saline solution (placebo control)
intravenous infusion over 20 minutes; twice on 1 study day
DEVICELaser Doppler flowmetry
blood flow measurements at the temporal neuroretinal rim of the optic nerve head
Intraocular pressure measurements
DEVICEHP-CMS patient monitor
blood pressure and pulse rate measurements
PROCEDURESuction cup method
The IOP will be raised by an 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Men aged between 18 and 35 years, nonsmokers * Body mass index between 15th and 85th percentile (Must et al. 1991) * Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant * Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant * Normal ophthalmic findings, ametropy \< 1 Dpt
Exclusion criteria
* Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study * Treatment in the previous 3 weeks with any drug * Symptoms of a clinically relevant illness in the 3 weeks before the first study day * History of hypersensitivity to the trial drug or to drugs with a similar chemical structure * History or presence of systemic or pulmonary hypertension, or other cardiac or pulmonary diseases * History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with, distribution, metabolism or excretion of study drugs * Blood donation during the previous 3 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ONH pressure-flow relationship | up to 3 study days |
Countries
Austria
Outcome results
None listed