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Adenosine Receptors Influence Ischemia-Reperfusion Injury

Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015
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: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double-Blind

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

Page last updated: August 23, 2015

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