The Effect of Ischaemic-Reperfusion in Man - A Bradykinin Dependent Pathway

Study Overview
=================
Brief Summary
-----------------
Heart attacks are usually caused by a blood clot blocking an artery supplying blood to the heart. Current treatments are designed to relieve 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.

Official Title
-----------------
The Effect of Ischaemic-Reperfusion in Man - A Bradykinin Dependent Pathway

Conditions
-----------------
Ischaemic Heart Diseases

Intervention / Treatment
-----------------
* Procedure: Forearm vascular study
* Drug: bradykinin receptor antagonist (HOE-140)
* Drug: Placebo (saline)


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Ischaemia 20 minutes. Blood pressure cuff will be inflated to 200mmHg around the upper arm for 20 minutes to induce ischaemia. Systemic infusion of placebo (saline). | Procedure: Forearm vascular study<br>* Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of vasodilators (Ach). Venous blood sampling via cannula in antecubital fossa.<br>Drug: Placebo (saline)<br>* Systemic infusion of placebo (saline).<br>|
| Active Comparator: 2<br>Ischaemia 20 minutes. Blood pressure cuff will be inflated to 200mmHg around the upper arm for 20 minutes to induce ischaemia. Systemic infusion of bradykinin receptor antagonist (HOE-140). | Procedure: Forearm vascular study<br>* Forearm blood flow measured by venous occlusion plethysmography during interarterial infusion of vasodilators (Ach). Venous blood sampling via cannula in antecubital fossa.<br>Drug: bradykinin receptor antagonist (HOE-140)<br>* Systemic infusion of bradykinin receptor antagonist (HOE-140).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forearm blood flow in response to vasodilators (ACh) and ischaemia reperfusion |  | 20 fixed timepoints during each study visit (3hrs) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in platelet-monocyte-binding after ischaemia reperfusion |  | 4 fixed timepoints during each study visit (3hrs) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ischaemia reperfusion, Bradykinin, Platelet activation, Endothelial function