Affiliations: Dresdner Institut für Herz‐ und Kreislaufforschung, Fortstraße 5, 01099 Dresden, Germany | Abteilung für Klinische Hämostaseologie und Transfusionsmedizin, Universität des Saarlandes, 66421 Homburg/Saar, Germany | Aventis, 65812 Bad Soden, Germany | Abteilung Biomaterialen, Universität Ulm, Albert‐Einstein‐Allee 47, 89081 Ulm, Germany
Note: [] Corresponding author: Prof. Dr. F. Jung, Dresdner Institut für Herz‐ und Kreislaufforschung, Forststraße 5, 01099 Dresden, Germany. Tel.: +49 351 8064190; Fax: +49 351 8064199; E‐mail: dihkf@saarmail.de.
Abstract: It was investigated whether the NO‐donor SIN‐1, the active metabolite of molsidomine, influenced the activation of platelets, the formation of circulating platelet aggregates, the spontaneous aggregation of platelets and the activation of the clotting system triggered by a body foreign surface in an in vitro closed‐loop perfusion model. With human platelet‐rich plasma at micromolar concentrations SIN‐1 exerted pronounced effects on the interaction between platelets and an exogenous surface. In the absence of SIN‐1, the number of circulating single platelets decreased significantly, which could be due either to the formation of circulating platelet aggregates or to the adhesion of platelets to the stent. Both these processes were blocked by the addition of SIN‐1. Moreover, the platelets exhibited hyperaggregability in the absence of SIN‐1 whereas the NO‐donor was able to completely inhibit spontaneous platelet aggregation. Similar results were obtained in flow cytometry experiments. Without SIN‐1, high platelet surface densities of both the GPIb/IX and GPIIb/IIIa receptors were observed. In addition, the density of the fibrinogen receptor increased significantly with the number of perfusion cycles. SIN‐1 was able to suppress the augmented GPIIb/IIIa receptor expression significantly. Molsidomine seemed to have the potential to reduce the incidence of thrombotic processes triggered by the exogenous surface of the stent.
Keywords: Haemocompatibility, coronary stents, in vitro, platelet aggregation, platelet activation
