Role of Endothelin- and Nitric Oxide-system in the Regulation of Optic Nerve Head Blood Flow During Changes in Ocular Perfusion Pressure

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).

Conditions

• Ocular Physiology
• Optic Disk
• Regional Blood Flow

Interventions

DRUG

NG-monomethyl-L-arginine (L-NMMA)

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

DRUG

Endothelin-1 (ET-1)

5 ng/kg/min intravenous infusion over 17 minutes; twice on 1 study day

DRUG

Physiologic saline solution (placebo control)

intravenous infusion over 20 minutes; twice on 1 study day

DEVICE

Laser Doppler flowmetry

blood flow measurements at the temporal neuroretinal rim of the optic nerve head

DEVICE

Goldmann applanation tonometer

Intraocular pressure measurements

DEVICE

HP-CMS patient monitor

blood pressure and pulse rate measurements

PROCEDURE

Suction 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 & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Gabriele Fuchsjaeger-Mayrl, MD,Univ.Doz. · Department of Clinical Pharmacology, Medical University of Vienna

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2008-01-31

Primary Completion

2014-11-30

Completion

2014-11-30

Countries

• Austria

Study Locations