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The most powerful protective mechanism against ischemia-reperfusion injury other than rapid reperfusion is ischemic preconditioning. 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 adenosine and morphine.
We, the researchers at Radboud University Nijmegen Medical Centre, have recently developed a method in which we can detect ischemia-reperfusion injury in the human forearm by using Annexin A5 scintigraphy (Rongen et al). With this method we will determine whether opioid receptors are involved in ischemic preconditioning. We expect to find that morphine can mimic ischemic preconditioning and that acute ischemic preconditioning can be blocked with the opioid receptor antagonist naloxon. 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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| morphine | Drug | |||
| naloxone | Drug | |||
| Technetium-TC99m-labeled Annexin A5 | Drug | |||
| forearm ischemic exercise | Procedure | |||
| ten minute forearm ischemia | Procedure |
| Measure | Description | Time Frame |
|---|---|---|
| Percentual difference in Annexin A5 targetting between the experimental and control arm 1 and 4 hours after intravenous injection |
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| Name | Affiliation | Role |
|---|---|---|
| Gerard Rongen, MD, Phd | Radboud University Nijmegen Medical Centre / Department of Pharmacology and Toxicology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre / Department of Pharmacology and Toxicology | Nijmegen | Gelderland | 6500 HB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15623546 | Background | Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27. |
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| ID | Term |
|---|---|
| D015427 | Reperfusion Injury |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| D009270 | Naloxone |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |