title: Influence of the direct NO-donor SIN-1 on the interaction between platelets and stainless steel stents under dynamic conditions.
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.
authors.affiliation: Dresdner Institut für Herz- und Kreislaufforschung, Fortstrasse 5, 01099 Dresden, Germany. dihkf@saarmail.de
authors.forename: F
authors.initials: F
authors.lastname: Jung
authors.forename: C
authors.initials: C
authors.lastname: Mrowietz
authors.forename: U T
authors.initials: UT
authors.lastname: Seyfert
authors.forename: R
authors.initials: R
authors.lastname: Grewe
authors.forename: R P
authors.initials: RP
authors.lastname: Franke
mesh_terms: D000328:Adult; D001672:Biocompatible Materials; D015415:Biomarkers / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013193:Stainless Steel; D015607:Stents
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D020030:Nitric Oxide Donors; D013193:Stainless Steel; C002385:linsidomine; D008981:Molsidomine