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Thromb Haemost 1997; 78(04): 1242-1248
DOI: 10.1055/s-0038-1657722
Rapid Communication
Schattauer GmbH Stuttgart

An in vivo Model for the Assessment of Acute Fibrinolytic Capacity of the Endothelium

David E Newby
1   The Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK
2   The Department of Cardiology, University of Edinburgh, Royal Infirmary, Edinburgh, UK
,
Robert A Wright
2   The Department of Cardiology, University of Edinburgh, Royal Infirmary, Edinburgh, UK
,
Christopher A Ludlam
3   The Department of Haematology, University of Edinburgh, Royal Infirmary, Edinburgh, UK
,
Keith A A Fox
2   The Department of Cardiology, University of Edinburgh, Royal Infirmary, Edinburgh, UK
,
Nicholas A Boon
2   The Department of Cardiology, University of Edinburgh, Royal Infirmary, Edinburgh, UK
,
David J Webb
1   The Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK
› Author Affiliations
Further Information

Publication History

Received 13 1997

Accepted after resubmission 27 May 1997

Publication Date:
12 July 2018 (online)

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Summary

The effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 μg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.

 

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