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

Purpose

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.

Condition	Intervention
Ischaemic Heart Diseases	Procedure: Forearm vascular study

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	The Effect of Ischaemic-Reperfusion and Ischaemic Preconditioning on the Endogenous Fibrinolysis in Man

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Diseases

U.S. FDA Resources

Further study details as provided by University of Edinburgh:

Primary Outcome Measures:

Net t-PA release from the endothelium after ischaemia reperfusion and ischaemic preconditioning [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in forearm blood flow after ischaemia reperfusion and ischaemic preconditioning [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Change in platelet-monocyte-binding after ischaemia reperfusion and ischaemic preconditioning [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	November 2008
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 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 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.
Active Comparator: 2 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 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.
Placebo Comparator: 3 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 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00789243

Locations

United Kingdom
University of Edinburgh, 49 Little France Crescent
Edinburgh, United Kingdom, EH16 4SB

Sponsors and Collaborators

University of Edinburgh

University of Aarhus

University of Oxford

Investigators

Study Director:	David E Newby, PhD, FRCP	University of Edinburgh
Study Director:	Rajesh K Kharbanda, PhD, FRCP	University of Oxford

More Information

No publications provided by University of Edinburgh

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pedersen CM, Barnes G, Schmidt MR, Bøtker HE, Kharbanda RK, Newby DE, Cruden NL. Ischaemia-reperfusion injury impairs tissue plasminogen activator release in man. Eur Heart J. 2012 Aug;33(15):1920-7. Epub 2011 Oct 11.

Pedersen CM, Cruden NL, Schmidt MR, Lau C, Bøtker HE, Kharbanda RK, Newby DE. Remote ischemic preconditioning prevents systemic platelet activation associated with ischemia-reperfusion injury in humans. J Thromb Haemost. 2011 Feb;9(2):404-7. No abstract available.

Responsible Party:	Christian M Pedersen, clinical research fellow, University of Edinburgh
ClinicalTrials.gov Identifier:	NCT00789243 History of Changes
Other Study ID Numbers:	CMP 2
Study First Received:	November 10, 2008
Last Updated:	October 22, 2010
Health Authority:	United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:

Ischaemia reperfusion
t-PA
Fibrinolysis
Endothelial function
Local and remote ischaemic preconditioning

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Ischemia
Coronary Disease

Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 23, 2013