Role of Nitrogen Oxide (NO) in the Control of Choroidal Blood Flow During a Decrease in Ocular Perfusion Pressure

Role of NO in the Control of Choroidal Blood Flow During a Decrease in Ocular Perfusion Pressure

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. For a long time it had been assumed that the choroid is a strictly passive vascular bed, which shows no autoregulation. However, recently several groups have identified some autoregulatory capacity of the human choroid. In the brain and the retina the mechanism behind autoregulation is most likely linked to changes in transmural pressure. In this model arterioles change their vascular tone depending on the pressure inside the vessel and outside the vessel. In the choroid, several observations argue against a direct involvement of arterioles. However, the mechanism behind choroidal autoregulation remains unclear.

In the present study autoregulation of the choroid will be investigated during a decrease in ocular perfusion pressure, which will be achieved by an increase in intraocular pressure. Pressure/flow relationships will be investigated in the absence or presence of a NO synthase inhibitor. As a control substance the alpha-receptor agonist phenylephrine will be used.

Study Overview

• Status: Completed
• Conditions: Regional Blood Flow; Microcirculation; Physiology, Ocular; Autoregulation
• Intervention / Treatment: Procedure: Suction cup application; Procedure: Laser Doppler flowmetry; Procedure: Measurement of intraocular pressure

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men aged between 19 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, ametropia < 3 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Phenylephrine (Neosynephrine®, Abbott Laboratories, North Chicago, IL, USA) dose: 1µg/(kg.min), infusion period 20 minutes	Procedure: Suction cup application; he IOP will be raised by a 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.; Procedure: Laser Doppler flowmetry; Measurement of choroidal blood flow; Procedure: Measurement of intraocular pressure
Active Comparator: 2; NG-monomethyl-L-arginine (L-NMMA, Clinalfa, Läufelfingen, Switzerland) dose: bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/(kg.min) over 15 minutes	Procedure: Suction cup application; he IOP will be raised by a 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.; Procedure: Laser Doppler flowmetry; Measurement of choroidal blood flow; Procedure: Measurement of intraocular pressure
Placebo Comparator: 3; Physiologic saline solution	Procedure: Suction cup application; he IOP will be raised by a 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.; Procedure: Laser Doppler flowmetry; Measurement of choroidal blood flow; Procedure: Measurement of intraocular pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
ocular perfusion pressure - choroidal blood flow relationship

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Gabriele Fuchsjager-Mayrl, MD, Department of Clinical Pharmacology, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): February 1, 2004
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Other Study ID Numbers: OPHT-270602