title: Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation.
abstract: Ventricular Assist Devices (VADs) have been used as bridges to heart transplantation. However, VAD circulation is complicated by the incidence of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are interrelated and linked to the activation of the glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, on platelet and neutrophil activation during simulated VAD circulation. Two groups of five in vitro VAD circuits were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation. Neutrophil elastase secretion was not affected by Tirofiban administration. Preconditioning of VAD circulation with Tirofiban attenuated platelet activation as demonstrated by a decrease in serum PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion indicates that the inflammatory response is not completely inhibited by Tirofiban administration. These results suggest that neutrophils may be activated by alternative mechanisms. Early complement activation has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions during VAD use.
authors.affiliation: Department of Physiology, University of Hawaii at Manoa, USA.
authors.forename: B O
authors.initials: BO
authors.lastname: King
authors.forename: E S
authors.initials: ES
authors.lastname: Whittow
authors.forename: D L
authors.initials: DL
authors.lastname: Serna
authors.forename: B U
authors.initials: BU
authors.lastname: Jones
authors.forename: J S
authors.initials: JS
authors.lastname: Eng
authors.forename: J C
authors.initials: JC
authors.lastname: Chen
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D003167:Complement Activation; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017997:Leukotriene C4; D010978:Platelet Factor 4; D014443:Tyrosine; D019272:Leukocyte Elastase; D000077466:Tirofiban