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

NCT00965393 | Completed

• 1 other identifier: CMP 5
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ischaemic Heart Diseases

Keywords

Ischaemia reperfusion; Platelet activation; Endothelial function; Remote ischaemic preconditioning; Bradykinin

Outcome Measures

Primary Outcomes (1)

• Change in forearm blood flow in response to vasodilators (ACh(, ischaemia reperfusion and ischaemic preconditioning

  20 fixed timepoints during each study visit (3hrs)

Secondary Outcomes (1)

• Change in platelet-monocyte-binding after ischaemia reperfusion and ischaemic preconditioning

  4 fixed timepoints during each study visit (3hrs)

Study Arms (2)

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).

Procedure: Forearm vascular study; Drug: Placebo

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).

Procedure: Forearm vascular study; Drug: bradykinin receptor antagonist (HOE-140)

Interventions

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.

1; 2

Placebo DRUG

Systemic infusion of placebo (saline)

1

bradykinin receptor antagonist (HOE-140) DRUG

Systemic infusion of bradykinin receptor antagonist (HOE-140)

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males between 18-65 years of ages.
• Non-smokers.

You may not qualify if:

• Any concurrent illness or chronic medical condition.
• Concurrent use of vasoactive medication.
• Smoking history.

Sponsors & Collaborators

• University of Edinburgh: lead
• University of Aarhus: collaborator
• University of Oxford: collaborator

Study Sites (1)

University of Edinburgh, 49 Little France Crescent

Edinburgh, EH16 4SB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 21873443 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Bradykinin Receptor Antagonists; icatibant

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• David E Newby, PhD, FRCP

  University of Edinburgh

  STUDY DIRECTOR

• Rajesh K Kharbanda, PhD, FRCP

  University of Oxford

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 19, 2009
• First Posted: August 25, 2009
• Study Start: August 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 25, 2010

Record last verified: 2010-10

Locations

GB (1)