Adenosine Receptors Influence Ischemia-Reperfusion Injury

Study Overview
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Brief Summary
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Ischemic preconditioning is defined as the development of tolerance to ischemia-reperfusion injury by a previous short bout of ischemia resulting in a marked reduction in infarct size. This mechanism can be mimicked by several pharmacological substances such as acetylcholine and adenosine. To detect ischemia-reperfusion injury in humans in vivo Kharbanda et al. developed a method in which endothelial dysfunction represents the effects of ischemic preconditioning. This method, however, uses acetylcholine to measure endothelial function before and after forearm ischemia. We, the investigators at Radboud University, hypothesize that the use of acetylcholine in this model reduces ischemia-reperfusion injury. Therefore, we will compare this protocol with a protocol in which endothelial function is only measured after ischemia. We expect an increase in ischemia-reperfusion injury when endothelial function is only measured after the forearm ischemia. After determining the optimal method to measure ischemia-reperfusion injury of the vascular endothelium we will determine the effect of acute and chronic caffeine, an adenosine receptor antagonist, on ischemic preconditioning. With this study we expect to find that adenosine mimics ischemic preconditioning of the vascular endothelium. Moreover, we expect to find that acute caffeine intake reduces ischemia-reperfusion injury whereas chronic caffeine intake does not. This study will increase our knowledge about the mechanism of ischemic preconditioning and may also provide leads to exploit this endogenous protective mechanism in a clinical setting.

Official Title
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Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium

Conditions
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Ischemia-Reperfusion Injury

Intervention / Treatment
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* Drug: acetylcholine
* Procedure: twenty minutes of forearm ischemia
* Procedure: three 5-minute periods of forearm ischemia
* Drug: adenosine
* Drug: caffeine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: acetylcholine|nan|
|Procedure: twenty minutes of forearm ischemia|nan|
|Procedure: three 5-minute periods of forearm ischemia|nan|
|Drug: adenosine|nan|
|Drug: caffeine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetylcholine, adenosine, caffeine, ischemic preconditioning