Choroidal Blood Flow Regulation During Isometric Exercise: Effects of Ca2+-Channel Blockade

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. In a previous project we were able to identify that the nitric oxide (NO) - system as well as the endothelin system are involved in choroidal blood flow regulation during isometric exercise.

In the present study autoregulation of the choroid during isometric exercise will be investigated and the pressure/flow relationships will be observed in the absence or presence of a calcium antagonist - nifedipine.

Study Overview

• Status: Completed
• Conditions: Ocular Physiology; Regional Blood Flow
• Intervention / Treatment: Drug: Placebo; Drug: Nifedipine (drug); Drug: L-Arginin (drug)

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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, ametropy more than 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: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; Placebo	Drug: Placebo; Placebo; Drug: Nifedipine (drug); Nifedipine (Adalat®, Bayer, Leverkusen, Germany) dose: 15µg/kg bolus infusion over 5 minutes; 0.2 µg/(kg.min) maintenance dose infusion period 25 minutes; Drug: L-Arginin (drug); L-Arginin (Clinalfa AG, Läufelfingen, Switzerland) 30% sodium chlorid solution, dose: 1g/min over 30 minutes
Active Comparator: 1; Nifedipine	Drug: Placebo; Placebo; Drug: Nifedipine (drug); Nifedipine (Adalat®, Bayer, Leverkusen, Germany) dose: 15µg/kg bolus infusion over 5 minutes; 0.2 µg/(kg.min) maintenance dose infusion period 25 minutes; Drug: L-Arginin (drug); L-Arginin (Clinalfa AG, Läufelfingen, Switzerland) 30% sodium chlorid solution, dose: 1g/min over 30 minutes
Active Comparator: 2; L-Arginin	Drug: Placebo; Placebo; Drug: Nifedipine (drug); Nifedipine (Adalat®, Bayer, Leverkusen, Germany) dose: 15µg/kg bolus infusion over 5 minutes; 0.2 µg/(kg.min) maintenance dose infusion period 25 minutes; Drug: L-Arginin (drug); L-Arginin (Clinalfa AG, Läufelfingen, Switzerland) 30% sodium chlorid solution, dose: 1g/min over 30 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Choroidal pressure-blood flow relationship	in total 3x 3 hours

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Gabriele Fuchsjäger-Mayrl, M.D., Department of Clinical Pharmacology, Medical University of Vienna

Publications and helpful links

General Publications

• Schmidl D, Prinz A, Kolodjaschna J, Polska E, Luksch A, Fuchsjager-Mayrl G, Garhofer G, Schmetterer L. Effect of nifedipine on choroidal blood flow regulation during isometric exercise. Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):374-8. doi: 10.1167/iovs.11-8536.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): April 1, 2006

Study Registration Dates

• First Submitted: January 19, 2006
• First Submitted That Met QC Criteria: January 19, 2006
• First Posted (Estimate): January 23, 2006

Study Record Updates

• Last Update Posted (Estimate): July 9, 2008
• Last Update Submitted That Met QC Criteria: July 8, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: Nifedipine; Choroidal blood flow; Isometric exercise; Choroidal autoregulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine
• Other Study ID Numbers: OPHT-110705