Adenosine Receptors Influence Ischemia-Reperfusion Injury

This study has suspended participant recruitment.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00184847
First received: September 12, 2005
Last updated: March 27, 2008
Last verified: March 2008

September 12, 2005
March 27, 2008
March 2005
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Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia
Percentual increase in forearm blood flowratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia
Complete list of historical versions of study NCT00184847 on ClinicalTrials.gov Archive Site
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Adenosine Receptors Influence Ischemia-Reperfusion Injury
Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium

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.

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Interventional
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Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Ischemia-Reperfusion Injury
  • Drug: acetylcholine
  • Procedure: twenty minutes of forearm ischemia
  • Procedure: three 5-minute periods of forearm ischemia
  • Drug: adenosine
  • Drug: caffeine
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Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
8
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Inclusion Criteria:

  • Healthy volunteers
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00184847
ACAD
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Radboud University
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Principal Investigator: Gerard Rongen, MD, PhD Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
Radboud University
March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP