title: Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and in-stent stenosis in a passive-coated stent.
abstract: OBJECTIVE
  To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting.
  
  
  METHODS
  Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks. Histological analysis of the stented arteries was performed after hematoxylin-eosin staining. Tissue factor (TF) staining and scanning electron microscopy (SEM) were performed in animals with acute stent thrombosis.
  
  
  RESULTS
  Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups. Follow-up angiography did not show significant in-stent stenosis in either bare or ATA-coated stents. However, histomorphometry revealed larger neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p<0.05) and outward plaque area (1.56+/-0.34 mm2 versus 0.61+/-0.12 mm2, p<0.05) in ATA-coated stents. Three-dimensional IVUS analysis showed analogous results, with significantly larger neointimal volume and outward plaque volume in ATA-coated stents. There was a slight increase in TF staining around the stent struts, while SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents versus the ATA-coated and bare metal stents.
  
  
  CONCLUSIONS
  RG-13577/ATA-coated stents lead to acute stent thrombosis. The ATA coating alone did not lead to acute events, but resulted in higher neointimal hyperplasia and expansive remodeling. These results underline the importance of preclinical studies before using new coated stents in human arteries.
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria, and Departmetn of Cardiology, Karolinska University Hospital at Huddinge, Stockholm, Sweden. Christoph.Strehblow@wienkav.at
authors.forename: Christoph
authors.initials: C
authors.lastname: Strehblow
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperker
authors.forename: Akos
authors.initials: A
authors.lastname: Hevesi
authors.forename: Rita
authors.initials: R
authors.lastname: Garamvölgyi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Petrasi
authors.forename: Maryam
authors.initials: M
authors.lastname: Shirazi
authors.forename: Christer
authors.initials: C
authors.lastname: Sylvén
authors.forename: Thomas
authors.initials: T
authors.lastname: Weiss
authors.forename: Chaim
authors.initials: C
authors.lastname: Lotan
authors.forename: Thea
authors.initials: T
authors.lastname: Pugatsch
authors.forename: Shmuel A
authors.initials: SA
authors.lastname: Ben-Sasson
authors.forename: Michael
authors.initials: M
authors.lastname: Orlowski
authors.forename: Dietmar
authors.initials: D
authors.lastname: Glogar
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
mesh_terms: D000818:Animals; D001312:Aurintricarboxylic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D006965:Hyperplasia; D008855:Microscopy, Electron, Scanning; D010642:Phenoxyacetates / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D015607:Stents / Q000009:adverse effects; D013552:Swine; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D017211:Treatment Failure; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D004338:Drug Combinations; D010642:Phenoxyacetates; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D016222:Fibroblast Growth Factor 2; C090697:2-(4-hydroxyphenoxy)acetic acid-formaldehyde polymer; D001312:Aurintricarboxylic Acid