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Platelet glycoprotein IIb/IIIa inhibitor attenuates complement activation during in vitro ventricular assist circulation. 1998

D L Serna, and J Huh, and H Ha, and S S Parhizgar, and J C Chen
Division of Cardiothoracic Surgery, University of California Irvine Medical Center, Orange 92868, USA.

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.

UI MeSH Term Description Entries
D003167 Complement Activation The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES. Activation, Complement,Activations, Complement,Complement Activations
D006353 Heart-Assist Devices Small pumps, often implantable, designed for temporarily assisting the heart, usually the LEFT VENTRICLE, to pump blood. They consist of a pumping chamber and a power source, which may be partially or totally external to the body and activated by electromagnetic motors. Artificial Ventricle,Heart Assist Device,Heart Ventricle, Artificial,Pumps, Heart-Assist,Vascular-Assist Device,Vascular-Assist Devices,Ventricle-Assist Device,Ventricular Assist Device,Artificial Heart Ventricle,Artificial Heart Ventricles,Artificial Ventricles,Assist Device, Heart,Assist Device, Ventricular,Assist Devices, Heart,Assist Devices, Ventricular,Device, Heart Assist,Device, Heart-Assist,Device, Vascular-Assist,Device, Ventricle-Assist,Device, Ventricular Assist,Devices, Heart Assist,Devices, Heart-Assist,Devices, Vascular-Assist,Devices, Ventricle-Assist,Devices, Ventricular Assist,Heart Assist Devices,Heart Ventricles, Artificial,Heart-Assist Device,Heart-Assist Pump,Heart-Assist Pumps,Pump, Heart-Assist,Pumps, Heart Assist,Vascular Assist Device,Vascular Assist Devices,Ventricle Assist Device,Ventricle, Artificial,Ventricle, Artificial Heart,Ventricle-Assist Devices,Ventricles, Artificial,Ventricles, Artificial Heart,Ventricular Assist Devices
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015842 Serine Proteinase Inhibitors Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. Serine Endopeptidase Inhibitor,Serine Endopeptidase Inhibitors,Serine Protease Inhibitor,Serine Protease Inhibitors,Serine Proteinase Antagonist,Serine Proteinase Antagonists,Serine Proteinase Inhibitor,Serine Proteinase Inhibitors, Endogenous,Serine Proteinase Inhibitors, Exogenous,Serine Protease Inhibitors, Endogenous,Serine Protease Inhibitors, Exogenous,Antagonist, Serine Proteinase,Endopeptidase Inhibitor, Serine,Inhibitor, Serine Endopeptidase,Inhibitor, Serine Protease,Inhibitor, Serine Proteinase,Protease Inhibitor, Serine,Proteinase Antagonist, Serine,Proteinase Inhibitor, Serine
D015926 Complement C3a The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE. C3a Complement,Complement 3a,Complement Component 3a,C3a, Complement,Complement, C3a,Component 3a, Complement
D019039 Platelet Glycoprotein GPIIb-IIIa Complex Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA. GPIIb-IIIa Receptors,Integrin alphaIIbbeta3,Glycoproteins IIb-IIIa,Integrin alpha-IIb beta-3,GPIIb IIIa Receptors,Glycoproteins IIb IIIa,Integrin alpha IIb beta 3,Platelet Glycoprotein GPIIb IIIa Complex,Receptors, GPIIb-IIIa,alphaIIbbeta3, Integrin,beta-3, Integrin alpha-IIb
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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