Why Do Some Grafts Used in Right Ventricular Outflow Tract Revalvulation Get Infected and Others Do Not?

Background: Right ventricular outflow tract (RVOT) reconstruction in congenital heart disease can be surgically done using cryopreserved pulmonary homograft (CH) and alternatively xenografts such as the bovine jugular vein (BJV) valved conduit. Despite this good therapeutic alternative, recent clinical studies report an increased risk of infective endocarditis (IE) in BJV. This raises the question of why such valves are more prone to IE than homografts.

Objectives: We investigate whether different graft tissues promote interactions with plasma components and blood cells and therefore enhance the risk for Staphylococcus aureus adhesion to the valvular tissue.

Methods: Tissues, prepared for clinical use, were incubated with fluorescently labeled fibrinogen (Fg) as one of abundant plasma proteins. Then, S. aureus adhesion to the same tissues was assessed under flow conditions using a parallel plate flow chamber after tissue preincubation with PBS, human plasma, albumin, or serum. Moreover, tissue susceptibility to interaction with platelets was evaluated upon perfusing whole blood using a colorimetric assay. To document a contribution of Fg-mediated pathway to the interplay bacteria-tissue-platelets, bacterial mutants and antiplatelet drugs were employed. Protein binding to tissues was quantified with fluorescence microscopy, and bacterial adhesion was evaluated by CFU counting on blood agar. Bacteria and platelets were visualized on the tissues with confocal or electron microscopy.

Results: Bovine pericardium patch presented higher protein binding (p < 0.05) compared with BJV and CH. Although not significant, there is a slight trend to higher Fg interaction with BJV than with CH. After incubation with plasma, S. aureus adhesion to BJV increased significantly under flow conditions compared with the respective controls (human serum p < 0.05 and albumin p < 0.01). Both bacterial and platelet adhesions to BJV were greater in relation to CH (p < 0.001 and p < 0.05, respectively). Moreover, deletion of clfA hampered bacterial adhesion to BJV (p = 0.07) as well as eptifibatide significantly reduced (p < 0.001) platelet reactivity toward BJV.

Conclusion: Our results indicate that the role of the Fg-mediated pathway is of vital importance for S. aureus recruitment to endovascular tissues. Future studies will focus on endothelialization of grafted tissues and how this affects lesion formation and development of valvular infection. Moreover, antiplatelet therapy will be addressed to study its effect on bacterial recruitment.