Clinical trial NCT00184847: Adenosine Receptors Influence Ischemia-Reperfusion Injury
Official title: Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Ischemia-Reperfusion Injury
Keywords: acetylcholine
adenosine
caffeine
ischemic preconditioning
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Healthy volunteers

Primary outcomes:
measure: Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
state: Gelderland
Study officials:
affiliation: Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
name: Gerard Rongen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1161/01.cir.103.12.1624.