The Effect of Ischaemic-Reperfusion and Ischaemic Preconditioning on the Endogenous Fibrinolysis in Man

Study Overview
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Brief Summary
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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 minimise 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 us to understand the mechanism by which ischaemia-reperfusion injury may occur and to devise new treatments for heart attacks.

Official Title
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The Effect of Ischaemic-Reperfusion and Ischaemic Preconditioning on the Endogenous Fibrinolysis in Man

Conditions
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Ischaemic Heart Diseases

Intervention / Treatment
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* Procedure: Forearm vascular study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males between 18-65 years of ages, non-smokers. Exclusion Criteria: Any concurrent illness or chronic medical condition. Concurrent use of vasoactive medication. Smoking history.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, local ischaemic preconditioning will be induced by inflating a cuff around the non-dominant arm to 200 mmHg for 5 mins followed by 5 mins of reperfusion. This cycle will be repeated 3 times. | Procedure: Forearm vascular study<br>* Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of substance P (2,4,8 pmol/min). Venous blood sampling via cannula in antecubital fossa.<br>|
| Active Comparator: 2<br>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. | Procedure: Forearm vascular study<br>* Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of substance P (2,4,8 pmol/min). Venous blood sampling via cannula in antecubital fossa.<br>|
| Placebo Comparator: 3<br>Prior to 20 mins of ischaemia induced by a blood pressure cuff inflated to 200 mmHg around the upper non-dominant arm, sham will be performed by inflating a cuff to 10 mmHg for 5 mins followed by 5 mins of deflation. This cycle will be repeated 3 times. | Procedure: Forearm vascular study<br>* Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of substance P (2,4,8 pmol/min). Venous blood sampling via cannula in antecubital fossa.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net t-PA release from the endothelium after ischaemia reperfusion and ischaemic preconditioning |  | Throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forearm blood flow after ischaemia reperfusion and ischaemic preconditioning |  | throughout the study | 
| Change in platelet-monocyte-binding after ischaemia reperfusion and ischaemic preconditioning |  | Throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischaemia reperfusion, t-PA, Fibrinolysis, Endothelial function, Local and remote ischaemic preconditioning