TIROFIBAN ADMINISTRATION ATTENUATES PLATELET - NEUTROPHIL CONJUGATION, BUT NOT THE INFLAMMATORY RESPONSE DURING VENTRICULAR ASSIST DEVICE CIRCULATION:

Purpose of Study: Ventricular Assist Devices (VADs) have been used as a bridge to heart transplantation. However, VAD circulation has associated side effects of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are inter-related and linked to the activation of the Glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of GP IIb/IIIa receptor inhibition with Tirofiban on platelet and neutrophil activation during simulated VAD circulation. Methods Used: Two groups of 5 in vitro VAD circuits were simulated with and without Tirofiban using 450cc human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring platelet aggregation, leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Baseline platelet aggregation was preserved by Tirofiban. PF4 production was decreased by Tirofiban. Platelet-neutrophil conjugation release of measured LTC4 was decreased in the presence of Tirofiban. Neutrophil elastase secretion was not affected by Tirofiban administration.FigureConclusion: Preconditioning of VAD circulation with Tirofiban attenuates platelet activation demonstrated by a decrease in measured PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion suggests that the inflammatory response is not completely inhibited by Tirofiban administration. Neutrophils are activated by alternative mechanisms and require further study.