The Effect of an α2-Adrenoceptor Antagonist (Yohimbine) on Dynamic Autoregulation in the Human Middle Cerebral Artery and Ophthalmic Artery

Ocular Physiology Clinical Trial

Official title:

The Effect of an α2-Adrenoceptor Antagonist (Yohimbine) on Dynamic Autoregulation in the Human Middle Cerebral Artery and Ophthalmic Artery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00814047
• Other study ID #: OPHT-280604
• Status: Completed
• Phase: Phase 4
• First received: December 22, 2008
• Last updated: December 22, 2008

Study information

• Verified date: December 2008
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

Blood flow autoregulation is defined as the ability of a tissue to maintain a relatively constant flow, despite moderate alterations in perfusion pressure. Similar to the cerebral, renal, coronary and skeletal muscle circulations, the ocular vascular bed shows the property of flow autoregulation. This homeostatic mechanism allows blood supply to the eye to match metabolic demand during daily activities, such as changes in posture, or in more critical conditions.

Autoregulation has been found to be a complex phenomenon, showing heterogeneity in its site and time course of action. Since metabolic, myogenic, neurogenic and possibly endothelium-related mechanisms may be involved, several factors may vary depending on the challenging stimulus, the vessel tone, or the degree of impairment of autoregulation.

To study the dynamics of ocular autoregulation, it is necessary to introduce a step disturbance (stimulus) in ocular perfusion pressure and to record the responses of ocular blood flow continuously before and after this step disturbance. The investigators have employed a mechanical noninvasive technique to induce an ocular perfusion pressure step disturbance without drugs or changes in the concentration of vasoactive substances in the blood by using the thigh cuff technique inducing a small step decrease in ocular perfusion pressure.

With this technique the investigators could show significant differences in the time response of blood velocities in the ophthalmic and middle cerebral artery. This clearly indicates different mechanisms to be responsible for autoregulatory mechanisms distal to the vessels.

Interestingly our results indicate that in the ophthalmic artery a late vasoconstriction occurs. Many previous investigations have demonstrated that sympathetic nerve stimulation causes vasoconstriction in the ocular circulation. Accordingly, the present study tests the hypothesis that α2-adrenoceptors are involved in the dynamic regulation of blood flow in the ophthalmic and middle cerebral artery after a step decrease in perfusion pressure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Men aged between 18 and 35 years

• Non-smokers

• Normal findings in medical history and pre-study screening 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoregulation
• Blood Flow Velocity
• Ocular Physiology

Intervention

Drug:
• Yohimbine hydrochloride

Locations

Country	Name	City	State
Austria	Department of Clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relation between blood pressure and local perfusion parameters.