on May 24, 2007
Published online before print May 24, 2007, doi: 10.1161/ATVBAHA.107.144576
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Submitted on June 25, 2006
Accepted on May 7, 2007
Effects of Unfractionated Heparin and Glycoprotein IIb/IIIa Antagonists Versus Bivalirdin on Myeloperoxidase Release From Neutrophils
Guohong Li ;
From the Carolina Cardiovascular Biology Center (A.C.K., J.C.Y., S.S.S.) and the School of Public Health (M.J.H.), The University of North Carolina, Chapel Hill; the Department of Medicine, Division of Cardiology (E.M.O.), Duke University Medical School, Durham, North Carolina; and the Division of Cardiovascular Medicine (G.L., Z.P., S.R.S., S.S.S.), The Gill Heart Institute, The University of Kentucky, Lexington.
* To whom correspondence should be addressed. E-mail: SusanSmyth{at}uky.edu.
Objectives--The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials.
Methods and Results--Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (P=0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury.
Conclusions--Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.
Key words: platelets • neutrophils • myeloperoxidase • percutaneous coronary intervention • adjunctive therapy
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