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

Study Overview
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Brief Summary
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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.

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

Conditions
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Physiology, Ocular, Microcirculation, Regional Blood Flow, Autoregulation

Intervention / Treatment
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* Procedure: Suction cup application
* Procedure: Laser Doppler flowmetry
* Procedure: Measurement of intraocular pressure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Phenylephrine (Neosynephrine®, Abbott Laboratories, North Chicago, IL, USA) dose: 1µg/(kg.min), infusion period 20 minutes | Procedure: Suction cup application<br>* 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.<br>Procedure: Laser Doppler flowmetry<br>* Measurement of choroidal blood flow<br>Procedure: Measurement of intraocular pressure<br> <br> |
| Active Comparator: 2<br>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<br>* 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.<br>Procedure: Laser Doppler flowmetry<br>* Measurement of choroidal blood flow<br>Procedure: Measurement of intraocular pressure<br> <br> |
| Placebo Comparator: 3<br>Physiologic saline solution | Procedure: Suction cup application<br>* 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.<br>Procedure: Laser Doppler flowmetry<br>* Measurement of choroidal blood flow<br>Procedure: Measurement of intraocular pressure<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ocular perfusion pressure - choroidal blood flow relationship |  |  |