The Influence of the 34C>T Variant in the AMPD1 Gene Ischemic Tolerance

Not Applicable

Completed

• Conditions: AMPD; Ischemic Tolerance

• Registration Number: NCT00319059
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Previous epidemiological studies have shown that in cardiovascular patients, the 34C\>T variant in the gene encoding for the enzyme Adenosine Mono Phosphate Deaminase (AMPD1) is associated with prolonged survival.

The 34 C\>T variant encodes a severely truncated, metabolically inactive protein. We hypothesize that during ischemia, in these patients AMP in preferentially converted into adenosine instead of IMP. Adenosine receptor stimulation, in turn, will increase resistance to ischemia-reperfusion in the myocardial tissue.

To test this hypothesis, 7 male healthy volunteers heterozygous for the 34C\>T variant will be selected from 100 healthy volunteers, which we have previously genotyped. These subjects will be compared with 7 matched control subjects. Individual ischemic tolerance will be assessed in the thenar muscle using 99mTc-Annexin A5 scintigraphy.

Briefly, the circulation of the nondominant forearm will be interrupted for 10 minutes by inflation of an upperarm cuff to 200mmHg en concomitantly, the subjects will perform isometric rhythmic handgripping until exhaustion. Immediately upon reperfusion, 400 MBq of 99mTc-Annexin A5 will be administered intravenously. Finally, 1 and 4 hours post-injection, scintigrapghi imaging of both hand will be performed. Targeting of annexin A5 will be expressed as percentage difference between the experimental and control hand.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-03
• Primary Completion: 2006-04
• Study Completion: 2006-04
• Study First Submitted: 2006-04-27
• Study First Submitted QC: 2006-04-27
• Study First Posted: 2006-04-27
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-21
• Last Update Posted: 2016-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 14

Inclusion Criteria

• male
• 18-40 years
• healthy
• AMPD1 34C>T variant (heterozygous) or matched control

Exclusion Criteria

• cardiovascular / pulmonary disease
• diabetes / hypertension

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
99mTc-Annexin A5 targeting