title: Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo.
abstract: OBJECTIVE
  This study was designed to examine whether or not intramural delivery of ST638 (a specific tyrosine kinase inhibitor) with biodegradable stent can suppress the restenotic changes of the coronary artery in vivo.
  
  
  BACKGROUND
  Clinical and animal studies demonstrated that restenosis after coronary intervention results from a combined effect of neointimal formation and geometric remodeling (decrease in total cross-sectional area). Thus, the most effective strategy to prevent the restenosis appears to inhibit both the neointimal formation and geometric remodeling by antiproliferative agent and stent, respectively. We have previously shown that ST638 markedly suppresses the restenotic changes of the porcine coronary artery when applied from the adventitial site.
  
  
  METHODS
  A poly-L-lactic acid biodegradable stent was coated with either ST638 (0.8 mg) or equimolar of its inactive metabolite, ST494. A pair of these stents were implanted alternatively in the left anterior descending or circumflex coronary artery in pigs (n=6). Three weeks after the procedure, coronary stenosis was assessed by angiography followed by histological examination.
  
  
  RESULTS
  Coronary stenosis was significantly less at the ST638 stent site than at the ST494 stent site (47+/-5% vs. 25+/-4%, p < 0.01). Histological examination also showed that the extent of neointimal formation and that of geometric remodeling were significantly less at the ST638 stent site than at the ST494 stent site (p < 0.05).
  
  
  CONCLUSIONS
  These results indicate that intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent overcomes the proliferative stimuli caused by balloon injury, the stent itself, and the drug coating on the stent, resulting in the suppression of the restenotic changes of the coronary artery in vivo. This strategy might also be useful in the clinical setting in humans.
authors.affiliation: Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamawaki
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: T
authors.initials: T
authors.lastname: Kozai
authors.forename: K
authors.initials: K
authors.lastname: Miyata
authors.forename: T
authors.initials: T
authors.lastname: Higo
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: T
authors.initials: T
authors.lastname: Shiraishi
authors.forename: H
authors.initials: H
authors.lastname: Tamai
authors.forename: K
authors.initials: K
authors.lastname: Igaki
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D002934:Cinnamates / Q000008:administration & dosage*; D003327:Coronary Disease / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004343:Drug Implants; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004867:Equipment Design; D019344:Lactic Acid; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011091:Polyesters; D011108:Polymers; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012008:Recurrence; D015607:Stents; D013440:Sulfides / Q000008:administration & dosage*; D013552:Swine
chemical_list: D002934:Cinnamates; D004343:Drug Implants; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D011091:Polyesters; D011108:Polymers; D013440:Sulfides; C060747:ST 638; D019344:Lactic Acid; C033616:poly(lactide); D011505:Protein-Tyrosine Kinases