Antiplatelet therapy abrogates platelet-assisted Staphylococcus aureus infectivity of biological heart valve conduits

Although recent advances in pulmonary valve replacement have enabled excellent hemodynamics, infective endocarditis remains a serious complication, particularly for implanted bovine jugular vein (BJV) conduits. We investigated contributions by platelets and plasma fibrinogen to endocarditis initiation on various grafts used for valve replacement. Thus, adherence of Staphylococcus aureus and platelets to 5 graft tissues was studied quantitatively in perfusion chambers, assisted by microscopic analysis. We also evaluated standard antiplatelet therapy to prevent onset of S aureus endocarditis. Of all tissues, bovine pericardium (BP) showed the greatest fibrinogen binding. Perfusion of all plasma-precoated tissues identified BP and BJVwall with the greatest affinity for S aureus. Perfusions of anticoagulated human blood over all tissues also triggered more platelet adhesion to BP and BJVwall as single platelets. Several controls confirmed that both S aureus and platelets were recruited on immobilized fibrinogen. In addition, perfusions (and controls) over plasma-coated tissues with whole blood, spiked with S aureus, revealed that bacteria exclusively bound to adhered platelets. Both the platelet adhesion and platelet-mediated S aureus recruitment required platelet αIIbβ3 and coated or soluble fibrinogen, respectively, interactions abrogated by the αIIbβ3-antagonist eptifibatide. Also, standard antiplatelet therapy (aspirin/ticagrelor) reduced the adherence of S aureus in blood to BJV 3-fold. Binding of plasma fibrinogen to especially BJV grafts enables adhesion of single platelets via αIIbβ3. S aureus then attaches from blood to (activated) bound platelet αIIbβ3 via plasma fibrinogen. Dual antiplatelet therapy appears a realistic approach to prevent endocarditis and its associated mortality. General experimental study design and impact of dual anti-platelet treatment on infective endocarditis initiation. Discs of various graft tissues were placed in a microparallel flow chamber, allowing perfusion of bacteria, suspended in whole blood over graft tissue surfaces in laminar flow conditions. The optimized setup enables assessment of bacterial adhesion by fluorescence microscopy and a serial dilution method to determine CFUs. Also, platelet adhesion in the flow chamber was quantitatively measured by a colorimetric assay, based on an acid phosphatase test. In the course of these studies, we uncovered that bacteria are exclusively recruited to graft cardiac tissues