Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Isometric Exercise in Healthy Humans

Sponsor

Medical University of Vienna (Other)

Overall Status

Completed

CT.gov ID

NCT00806741

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Autoregulation is defined as the ability of a vascular bed to adapt its vascular resistance to changes in perfusion pressure. In the eye, several studies have reported that retinal blood flow is autoregulated over a wide range of ocular perfusion pressures. The investigators recently showed that nitric oxide (NO) is a key metabolite in the regulation of vascular tone in the eye and plays an important role in the blood flow autoregulation of the choroidal circulation. However, no data is yet available for the optic nerve head. Thus, the present study is designed to test the hypothesis that NO plays also a role in optic nerve head blood flow autoregulation. Therefore, subjects will perform squatting to increase systemic perfusion pressure during administration of either a nitric oxide synthase inhibitor (L-NMMA), an α-receptor agonist (phenylephrine) or placebo. Optic nerve head blood flow will be continuously measured during the procedure to investigate optic nerve head autoregulation.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: NG-monomethyl-L-arginine (L-NMMA) Drug: Phenylephrine Drug: Physiological saline solution (as placebo) Device: Laser Doppler Flowmetry Device: Goldmann applanation tonometer Other: squatting	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Isometric Exercise in Healthy Humans

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 NG-monomethyl-L-arginine (L-NMMA)	Drug: NG-monomethyl-L-arginine (L-NMMA) bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes Device: Laser Doppler Flowmetry blood flow measurements at the temporal neuroretinal rim of the optic nerve head Device: Goldmann applanation tonometer intraocular pressure measurements Other: squatting Subjects will perform squatting for 6 minutes while blood flow is measured
Active Comparator: 2 Phenylephrine	Drug: Phenylephrine 1μg/kg/min, infusion period 20 minutes Device: Laser Doppler Flowmetry blood flow measurements at the temporal neuroretinal rim of the optic nerve head Device: Goldmann applanation tonometer intraocular pressure measurements Other: squatting Subjects will perform squatting for 6 minutes while blood flow is measured
Placebo Comparator: 3 Physiological saline solution	Drug: Physiological saline solution (as placebo) infusion period 20 minutes Device: Laser Doppler Flowmetry blood flow measurements at the temporal neuroretinal rim of the optic nerve head Device: Goldmann applanation tonometer intraocular pressure measurements Other: squatting Subjects will perform squatting for 6 minutes while blood flow is measured

Arm

Intervention/Treatment

Active Comparator: 1

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

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

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

Device: Laser Doppler Flowmetry

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

Device: Goldmann applanation tonometer

intraocular pressure measurements

Other: squatting

Subjects will perform squatting for 6 minutes while blood flow is measured

Active Comparator: 2

Phenylephrine

Drug: Phenylephrine

1μg/kg/min, infusion period 20 minutes

Device: Laser Doppler Flowmetry

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

Device: Goldmann applanation tonometer

intraocular pressure measurements

Other: squatting

Subjects will perform squatting for 6 minutes while blood flow is measured

Placebo Comparator: 3

Physiological saline solution

Drug: Physiological saline solution (as placebo)

infusion period 20 minutes

Device: Laser Doppler Flowmetry

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

Device: Goldmann applanation tonometer

intraocular pressure measurements

Other: squatting

Subjects will perform squatting for 6 minutes while blood flow is measured

Outcome Measures

Primary Outcome Measures

Optic nerve head pressure-flow relationship [in total 6x on 3 study days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and women aged between 18 and 35 years, nonsmokers
Men and women will be included in equal parts
Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
Normal findings in the laboratory testings unless the investigator considers an abnormality to be clinically irrelevant
Normal ophthalmic findings, ametropia less than 3 diopters

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 (except intake of oral contraceptives)
Symptoms of a clinically relevant illness in the 3 weeks before the first study day
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
Pregnancy