title: Beneficial Effects of a Novel Bioabsorbable Polymer Coating on Enhanced Coronary Vasoconstricting Responses After Drug-Eluting Stent Implantation in Pigs in Vivo.
abstract: OBJECTIVE
  The aim of this study was to examine which component of drug-eluting stents (DES) plays a major role in enhanced coronary vasoconstricting responses after DES implantation in pigs.
  
  
  BACKGROUND
  Recent studies have reported unremitting angina due to vasomotion abnormalities even after successful DES implantation. However, it remains to be elucidated which component of DES (metal stent, polymer coating, or antiproliferative drug) is responsible for DES-induced coronary hyperconstricting responses.
  
  
  METHODS
  We developed poly-dl-lactic acid and polycaprolactone (PDLLA-PCL) copolymer technology with higher biocompatibility that is resorbed within 3 months. Four types of coronary stents were made: 1) a stent with polylactic acid (PLA) polymer coating containing antiproliferative drug (P1+D+); 2) a stent with PLA polymer coating alone without any drug (P1+D-); 3) a stent with novel PDLLA-PCL polymer coating alone (P2+D-); and 4) a bare metal stent (P-D-). The 4 stents were randomly deployed in the left anterior descending and left circumflex coronary arteries in 12 pigs.
  
  
  RESULTS
  After 1 month, coronary vasoconstriction by intracoronary serotonin was enhanced at P1+D+ and P1+D- stent edges compared with P2+D- and P-D- stent edges and was prevented by a specific Rho-kinase (a central molecule of coronary spasm) inhibitor, hydroxyfasudil. Immunostainings showed that inflammatory changes and Rho-kinase activation were significantly enhanced at P1+D+ and P1+D- sites compared with P2+D- and P-D- sites. There were significant positive correlations between the extent of inflammation or Rho-kinase expression/activation and that of coronary vasoconstriction.
  
  
  CONCLUSIONS
  These results indicate the important roles of PLA polymer coating in DES-induced coronary vasoconstricting responses through inflammatory changes and Rho-kinase activation in pigs in vivo, which are ameliorated by PDLLA-PCL copolymers.
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Kensuke
authors: K
authors: Nishimiya
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: matsumoto@cardio.med.tohoku.ac.jp.
authors: Yasuharu
authors: Y
authors: Matsumoto
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hironori
authors: H
authors: Uzuka
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Tsuyoshi
authors: T
authors: Ogata
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Michinori
authors: M
authors: Hirano
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Tomohiko
authors: T
authors: Shindo
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yuhi
authors: Y
authors: Hasebe
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Ryuji
authors: R
authors: Tsuburaya
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takashi
authors: T
authors: Shiroto
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Jun
authors: J
authors: Takahashi
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Kenta
authors: K
authors: Ito
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hiroaki
authors: H
authors: Shimokawa
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D003331:Coronary Vessels; D054855:Drug-Eluting Stents; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid; D023421:Models, Animal; D011091:Polyesters; D011108:Polymers; D013552:Swine; D017540:Tunica Media / Q000473:pathology; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D020099:Coated Materials, Biocompatible; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D019344:Lactic Acid; C033616:poly(lactide); D054460:rho-Associated Kinases
keywords: Rho-kinase; inflammation; polymers; stents