Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

Voisard, R; Stemberger, A; Baur, R; Herter, T; Hähnel, I; Resch, A; Seliger, C; Hemmer, W; Hannekum, A; Hombach, V; Alt, E

doi:10.1016/j.ijcard.2004.05.059

Benutzer: Gast

2005

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Titel:: Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.
Dokumenttyp:: Journal Article
Autor(en):: Voisard, R; Stemberger, A; Baur, R; Herter, T; Hähnel, I; Resch, A; Seliger, C; Hemmer, W; Hannekum, A; Hombach, V; Alt, E
Abstract:: BACKGROUND: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating. METHODS AND RESULTS: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining. CONCLUSIONS: Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.
Zeitschriftentitel:: Int J Cardiol
Jahr:: 2005
Band / Volume:: 102
Heft / Issue:: 3
Seitenangaben Beitrag:: 425-33
Sprache:: eng
Volltext / DOI:: doi:10.1016/j.ijcard.2004.05.059
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/16004887
Print-ISSN:: 0167-5273
TUM Einrichtung:: Institut für Experimentelle Onkologie und Therapieforschung
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Ehemalige Einrichtungen Institut für Experimentelle Onkologie und Therapieforschung 2005