Adenosine Receptors Influence Ischemia-Reperfusion Injury
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.
Allocation: Randomized, Control: Placebo Control, Intervention Model: Crossover Assignment, Masking: Double-Blind
acetylcholine, twenty minutes of forearm ischemia, three 5-minute periods of forearm ischemia, adenosine, caffeine
Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00184847
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Ischemic Preconditioning, Myocardial
Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.
The branch of medicine dealing with the fetus and infant during the perinatal period. The perinatal period begins with the twenty-eighth week of gestation and ends twenty-eight days after birth. (From Dorland, 27th ed)
A technique in which tissue is rendered resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. (Am J Physiol 1995 May;268(5 Pt 2):H2063-7, Abstract)
An acylated inactive complex of streptokinase and human lysine-plasminogen. After injection, the acyl group is slowly hydrolyzed, producing an activator that converts plasminogen to plasmin, thereby initiating fibrinolysis. Its half-life is about 90 minutes compared to 5 minutes for TPA; (TISSUE PLASMINOGEN ACTIVATOR); 16 minutes for UROKINASE-TYPE PLASMINOGEN ACTIVATOR and 23 minutes for STREPTOKINASE. If treatment is initiated within 3 hours of onset of symptoms for acute myocardial infarction, the drug preserves myocardial tissue and left ventricular function and increases coronary artery patency. Bleeding complications are similar to other thrombolytic agents.
Vesicular Acetylcholine Transport Proteins
Vesicular amine transporter proteins that transport the neurotransmitter ACETYLCHOLINE into small SECRETORY VESICLES. Proteins of this family contain 12 transmembrane domains and exchange vesicular PROTONS for cytoplasmic acetylcholine.
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