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| Name | Class |
|---|---|
| University of Aarhus | OTHER |
| University of Oxford | OTHER |
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Heart attacks are usually caused by a blood clot blocking an artery supplying blood to the heart. Current treatments are designed at relieving this blockage as quickly as possible to minimize damage to the heart muscle. However in restoring the supply of blood local damage known as "ischaemia-reperfusion injury" may occur. The aim of this study is to assess how clot forming and clot dissolving pathways are affected during this process, and examine the role of a natural inflammatory hormone, bradykinin. This will help the investigators to understand the mechanism by which ischaemia-reperfusion injury may occur and to devise new treatments for heart attacks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Placebo Comparator | Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, remote ischaemic preconditioning will be induced by inflating a cuff around the dominant arm to 200 mmHg for 5 mins followed by 5 mins of reperfusion. This cycle will be repeated 3 times. Systemic infusion of placebo (saline). |
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| 2 | Active Comparator | Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, remote ischaemic preconditioning will be induced by inflating a cuff around the dominant arm to 200 mmHg for 5 mins followed by 5 mins of reperfusion. This cycle will be repeated 3 times. Systemic infusion of bradykinin receptor antagonist (HOE-140). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Forearm vascular study | Procedure | Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of vasodilators (Ach). Venous blood sampling via cannula in antecubital fossa. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in forearm blood flow in response to vasodilators (ACh(, ischaemia reperfusion and ischaemic preconditioning | 20 fixed timepoints during each study visit (3hrs) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in platelet-monocyte-binding after ischaemia reperfusion and ischaemic preconditioning | 4 fixed timepoints during each study visit (3hrs) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David E Newby, PhD, FRCP | University of Edinburgh | Study Director |
| Rajesh K Kharbanda, PhD, FRCP | University of Oxford | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Edinburgh, 49 Little France Crescent | Edinburgh | EH16 4SB | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21873443 | Derived | Pedersen CM, Schmidt MR, Barnes G, Botker HE, Kharbanda RK, Newby DE, Cruden NL. Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man. Heart. 2011 Nov;97(22):1857-61. doi: 10.1136/heartjnl-2011-300323. Epub 2011 Aug 26. |
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| Placebo | Drug | Systemic infusion of placebo (saline) |
|
| bradykinin receptor antagonist (HOE-140) | Drug | Systemic infusion of bradykinin receptor antagonist (HOE-140) |
|
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D065168 | Bradykinin Receptor Antagonists |
| C065679 | icatibant |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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