title: Development of a prostacyclin-agonist-eluting aortic stent graft enhancing biological attachment to the aortic wall.
abstract: OBJECTIVE
  Stent graft-related complications, including endoleaks and graft migration, are partly attributed to insufficient graft attachment to the aortic wall. ONO-1301, a stable synthetic prostacyclin agonist, reportedly reorganizes extracellular matrices, enhancing tissue healing. We hypothesized that ONO-1301-eluting stent grafts may strengthen graft attachment to the aortic wall.
  
  
  METHODS
  Polylactic acid polymer-conjugated ONO-1301, which releases ONO-1301 into adjacent tissues over 3 months (ONO(+) group), or polylactic acid polymer only (ONO(-) group) was coated onto the stent graft and placed in the descending thoracic aorta of canines weighing 16 to 20 kg under fluoroscopic guidance. Examinations occurred at 1, 2, or 3 months postoperatively (n = 6 for each time point and group).
  
  
  RESULTS
  ONO-1301 aortic-wall concentrations were within the effective range even at 3 months. The maximal load for tearing the graft from the aortic wall ex vivo was significantly greater in the ONO(+) group than in the ONO(-) group (117.1%±44.4%, 133.9%±23.2%, and 119.9%±13.5% at 1, 2, and 3 months, respectively; P=.0007). Immunohistochemical examination revealed abundant α-smooth muscle actin-positive cells in the neointima in both groups. The fibrotic area between the graft and the aortic wall was significantly larger (P<.0001), and migrating cells into the graft fabric were significantly greater (P=.0003) in the ONO(+) group than in the ONO(-) group.
  
  
  CONCLUSIONS
  In canines, the ONO-1301-eluting stent graft enhanced tissue reorganization and improved the attachment between the graft and the aortic wall. This new device may be useful in preventing inadequate graft attachment to the aortic wall.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Shirakawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kuratani
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: sawa-p@surg1.med.osaka-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015415:Biomarkers / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D054855:Drug-Eluting Stents; D057867:Endoleak / Q000209:etiology / Q000517:prevention & control; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005240:Feasibility Studies; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005548:Foreign-Body Migration / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058426:Neointima; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D044062:Prostaglandins I / Q000819:agonists* / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D044062:Prostaglandins I; D011725:Pyridines; C105488:ONO 1301; D019344:Lactic Acid; C033616:poly(lactide)