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
  Purpose

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.


Condition Intervention
Ischemia-Reperfusion Injury
Drug: acetylcholine
Procedure: twenty minutes of forearm ischemia
Procedure: three 5-minute periods of forearm ischemia
Drug: adenosine
Drug: caffeine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Official Title: Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia

Estimated Enrollment: 8
Study Start Date: March 2005
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00184847

Locations
Netherlands
Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Gerard Rongen, MD, PhD Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00184847     History of Changes
Other Study ID Numbers: ACAD
Study First Received: September 12, 2005
Last Updated: March 27, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
acetylcholine
adenosine
caffeine
ischemic preconditioning

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Acetylcholine
Adenosine
Caffeine
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-Arrhythmia Agents
Central Nervous System Stimulants
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents

ClinicalTrials.gov processed this record on August 18, 2014