Clinical Trial: The Effect of A2A Adrenoceptor Stimulation on the Diameter of Retinal Arterioles During Hypoxia in Vivo

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: The Effect of A2A Adrenoceptor Stimulation on the Diameter of Retinal Arterioles During Hypoxia in Vivo

Brief Summary:

The purpose is to investigate how the adenosine affects the diameter regulation of retinal arterioles during changes in oxygen tension. A deeper understanding of the mechanisms involved in diameter regulation of retinal arterioles during changes in oxygen tension can be used to obtain a more detailed understanding of diseases where changes in the diameter regulation of retinal vessels are involved in the disease pathogenesis and possibly point to new therapeutic options for patients with retinal vascular disease, such as diabetic retinopathy and retinal vein thrombosis.

Preliminary, a routine ophthalmological evaluation, measurement of blood pressure, and electrocardiogram will be preformed to insure that only healthy test persons are included in the study.

The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order.

Protocol 1: Using the DVA, a video recording will capture the diameter of retinal vessels and the changes occurring during stimulation with flickering light. The recording lasts 4.5 minutes and is preformed before and after intravenous injection of adenosine.

Protocol 2: The procedures are similar to those of protocol 1 but are performed during breathing of a gas mixture with a reduced oxygen tension to 12,5 %, which results in a reduced oxygen saturation in the blood to 85-90 %.


Detailed Summary:

Background:

Occlusion of the retinal vessels leading to retinal ischaemia and hypoxia is an important element in the pathophysiology of the major vision threatening diseases in the Western World. The hypoxic areas release vasodilating factors that induce vasodilatation in adjacent retinal areas in order to increase blood flow and retinal oxygenation. An understanding of the mechanisms underlying this vasodilatation may help identifying new therapeutic principles for modulating retinal blood flow during changes in retinal blood flow secondary to hypoxia and other diseases.

The present study:

Two working hypotheses will be tested: 1) That systemic administration of an A2A adrenoceptor agonist affects retinal blood flow independently of its systemic effects. 2) That the vasodilating effect of A2A adrenoceptor stimulation and the vasodilating effects of systemic hypoxia and increased retinal metabolism induced by flicker stimulation are additive.

Methods:

The diameter of retinal vessels are measured using the Dynamic Vessel Analyser (DVA). This apparatus performs video recordings of the ocular fundus, and the single images in the video sequences are grabbed for computerised analysis. Special software enables calculation of the diameter of the vessel on the basis of the distance between the vessel borders. The fact that images are grabbed real time (25 times per second) allows the detection of immediate diameter changes when the retinal metabolism is increased by exposure to flickering light (metabolic autoregulation).

The A2A adrenoceptor agonist regadenoson is administered during continuous ECG monitoring as a single intravenous
Sponsor: University of Aarhus

Current Primary Outcome: Diameter responses of retinal arterioles [ Time Frame: 11 minutes ]

The main outcome variable of the DVA is the width measurement of the selected vessel(s), expressed in units of measurement (UM). In a normal Gullstrand eye, 1 UM is equivalent to 1 µm. For the stimulation with flicker light, the outcome is defined as the percent change from baseline.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Blood pressure [ Time Frame: The blood pressure is measured during the last 40 seconds in each phase using an oscillometric technique on the left arm. ]
    mmHg
  • Systemic arterial saturation [ Time Frame: The systemic arterial saturation is registered at the beginning and half way through each examination phase and during the 2 min break where the drug Regadenoson is injected. ]
    Percentage
  • Intraocular pressure [ Time Frame: The intraocular pressure is measured before and after the drug administration (time point 280 and 350 sec) and after the second DVA examination is terminated (time point 670 sec). ]
    mmHg


Original Secondary Outcome: Same as current

Information By: University of Aarhus

Dates:
Date Received: March 10, 2017
Date Started: March 22, 2017
Date Completion: November 2017
Last Updated: March 24, 2017
Last Verified: March 2017