title: Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.
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.
  
  
  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.
authors: Department of Internal Medicine II-Cardiology, University of Ulm, Germany. rainer.voisard@medizine.uni-ulm.de
authors: Rainer
authors: R
authors: Voisard
authors: Axel
authors: A
authors: Stemberger
authors: Regine
authors: R
authors: Baur
authors: Tina
authors: T
authors: Herter
authors: Iris
authors: I
authors: Hähnel
authors: Ansgar
authors: A
authors: Resch
authors: Christian
authors: C
authors: Seliger
authors: Wolfgang
authors: W
authors: Hemmer
authors: Andreas
authors: A
authors: Hannekum
authors: Vinzenz
authors: V
authors: Hombach
authors: Eckhard
authors: E
authors: Alt
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D001026:Coronary Artery Bypass; D023903:Coronary Restenosis / Q000517:prevention & control*; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage*; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D015607:Stents
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D016285:Iloprost; D017239:Paclitaxel