Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?

Radboud University Medical Center20 enrolled

Overview

The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.

Dipyridamole has been proven to reduce targeting of Annexin A5 in responses to ischemic exercise, indicating protection against ischemia-reperfusion injury in humans (pharmacological preconditioning). Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury. We hypothesize that endogenous adenosine mediates the protective effect of dipyridamole against ischemia-reperfusion injury. Therefore the adenosine receptor antagonist caffeine will reduce the benefit of dipyridamole on forearm ischemia-reperfusion injury.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Cardiovascular Disease Ischemia-Reperfusion Injury

Interventions

DipyridamoleDRUG

Dipyridamole 2x200mg 7day per os

caffeineDRUG

caffeine 4mg/kg iv

Eligibility

Sex: MALEMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male * Age between 18-50yr. Exclusion Criteria: * cardiovascular disease * hypertension (systole \> 140 mmHg, diastole \> 90 mmHg) * hypercholesterolemia (random total cholesterol \> 6.5 mmol/l) * diabetes mellitus (fasting glucose \> 7.0 mmol/L or random glucose \> 11.0 mmol/L) * asthma (recurrent episodes of dyspnea and wheezing, or usage of prescribed inhalation medication: i.e. corticosteroids or B2-agonists) * participation in any clinical trial during the last 60 days prior to this study. * administration of two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.

Locations (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Outcomes

Primary Outcomes

Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion

Time frame: 60 and 240 minutes after ischemic exercise

Secondary Outcomes

Plasma dipyridamole concentration

Time frame: at the morning of day 7 of treatment with dipyridamole/placebo

ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)

Time frame: before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol)

Workload (duration of exercise and developed force)

Time frame: during 10 minutes of ischemic exercise

Data from ClinicalTrials.gov

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