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(Circulation. 2003;108:536.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Platelet Glycoprotein IIb/IIIa Receptor Blockade Improves Vascular Nitric Oxide Bioavailability in Patients With Coronary Artery Disease

Thomas Heitzer, MD; Isabel Ollmann, BS; Katharina Köke, BS; Thomas Meinertz, MD; Thomas Munzel, MD

From the Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik III, Kardiologie und Angiologie, Hamburg, Germany.

Correspondence to Thomas Heitzer, Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik III, Abteilung Kardiologie und Angiologie, Martinistrasse 52, 20246 Hamburg, Germany. E-mail heitzer{at}uke.uni-hamburg.de

Received March 18, 2003; revision received May 8, 2003; accepted May 9, 2003.

Background— Platelet glycoprotein IIb/IIIa receptor blockade not only enhances epicardial flow but also improves microvascular perfusion. Inhibition of abnormal platelet–endothelial interactions may contribute to this beneficial effect. The present study was designed to determine whether glycoprotein IIb/IIIa receptor blockade influences endothelial vasomotor function and NO bioactivity in patients with coronary artery disease.

Methods and Results— Forty patients with symptomatic coronary artery stenosis were studied before planned percutaneous coronary intervention. By using venous occlusion plethysmography, endothelium-dependent and -independent vasodilation was determined by measuring forearm blood flow responses to acetylcholine with and without N^G-monomethyl-L-arginine (L-NMMA) and sodium nitroprusside. Vascular function tests were repeated during glycoprotein IIb/IIIa receptor blockade by tirofiban in 27 patients and by eptifibatide in 13 patients. A subgroup of 10 patients was retested 6 hours after stopping infusion of tirofiban. Glycoprotein IIb/IIIa receptor blockade by both substances improved acetylcholine-induced vasodilation and L-NMMA responses. Six hours after withdrawal of tirofiban infusion, the beneficial effects were not evident. Sodium nitroprusside–induced vasodilation was not changed by glycoprotein IIb/IIIa receptor blockade.

Conclusions— These findings support the concept that abnormal platelet-endothelial interactions contribute to endothelial dysfunction and impaired NO bioactivity in patients with symptomatic coronary artery disease.

Key Words: coronary artery disease • platelets • endothelial dysfunction • nitric oxide

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