title: Platelet glycoprotein IIb/IIIa inhibitor attenuates complement activation during in vitro ventricular assist circulation.
abstract: Complement activity and platelet glycoprotein (GP) IIb/IIIa dysfunction have been demonstrated during in vitro ventricular assist device circulation. Platelets contain C1 serine protease inhibitor (C1 INH) in secretory granules, which normally regulates complement. Complement activity may result from a loss of platelet regulation on complement during ventricular assist device circulation as platelets lose viability. The purpose of this study was to assess the ability of a platelet GP IIb/IIIa receptor inhibitor to attenuate ventricular assist device associated complement activation during in vitro ventricular assisted circulation. Eight in vitro nonpulsatile centrifugal ventricular assist device circuits were simulated for 4 days using 450 ml fresh human whole blood. Cardiac index, temperature, pH, PO2, PCO2, Ca, glucose, and activated clotting time were maintained at physiologic levels. Levels of C1 INH and C3a were measured with and without a reversible glycoprotein IIb/IIIa inhibitor (MK-383). Concentrations of C1 INH increase on exposure to ventricular assist device, and decrease to a plateau within 12 hr. The decrease in circulating unbound C1 INH was attenuated with pre treatment with MK-383. Concentrations of C3a increase 34 fold within 4 hr of exposure to a ventricular assist device with and 22 fold without pre treatment with MK-383. These findings suggest that protection of the platelet GP IIb/IIIa complex delays complement activation during in vitro ventricular assist device circulation.
authors.affiliation: Division of Cardiothoracic Surgery, University of California Irvine Medical Center, Orange 92868, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Serna
authors.forename: J
authors.initials: J
authors.lastname: Huh
authors.forename: H
authors.initials: H
authors.lastname: Ha
authors.forename: S S
authors.initials: SS
authors.lastname: Parhizgar
authors.forename: J C
authors.initials: JC
authors.lastname: Chen
mesh_terms: D003167:Complement Activation; D015926:Complement C3a / Q000032:analysis; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015842:Serine Proteinase Inhibitors / Q000097:blood
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015842:Serine Proteinase Inhibitors; D015926:Complement C3a