Adenosine Receptors Influence Ischemia-Reperfusion Injury
Information source: Radboud University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ischemia-Reperfusion Injury
Intervention: acetylcholine (Drug); twenty minutes of forearm ischemia (Procedure); three 5-minute periods of forearm ischemia (Procedure); adenosine (Drug); caffeine (Drug)
Phase: N/A
Status: Suspended
Sponsored by: Radboud University Official(s) and/or principal investigator(s):
Gerard Rongen, MD, PhD, Principal Investigator, Affiliation: Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
Summary
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.
Clinical Details
Official title: Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium
Study design: Randomized, Double-Blind, Placebo Control, Crossover Assignment
Primary outcome: Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Healthy volunteers
Locations and Contacts
Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology, Nijmegen, Gelderland 6500 HB, Netherlands
Additional Information
Related publications: 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.
Starting date: March 2005
Last updated: March 27, 2008
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