title: Dose-dependent vascular response following delivery of sirolimus via fast releasing, biodegradable polymer stent matrix: an experimental study in the porcine coronary model of restenosis.
abstract: BACKGROUND
  Fast releasing, rapamycin-eluting stents, although safe, showed inferior results with regard to inhibition of restenosis.
  
  
  OBJECTIVE
  Therefore, we report vascular effects of a novel, biodegradable polymer stent matrix with elevated sirolimus dose and fast release kinetics (ed-frSES, Alex, Balton) in the porcine coronary in-stent restenosis model.
  
  
  METHODS
  A total of 19 stents were implanted with 120% overstretch in the coronary arteries of seven domestic pigs: seven ed-frSES with 1.3 μg/mm2 of sirolimus, eight frSES with 1 μg/mm2 of sirolimus, and eight bare metal stents (BMS). For the following 28 days, coronary angiography was performed, animals were sacrificed, and the stented segments harvested for histopathological evaluation.
  
  
  RESULTS
  In angiography at 28 days the late lumen loss was lowest in the elevated dose sirolimus eluting stent (SES) (ed-frSES: 0.20 ± 0.2 vs. frSES: 0.80 ± 0.5 vs. BMS: 0.96 ± 0.5 mm, p < 0.01). This was confirmed in the morphometric evaluation in histopathology as represented by a significant and dose-dependent decrease in the percentage area of stenosis (ed-frSES: 22.4 ± 12.7% vs. frSES: 35 ± 10.7% vs. BMS: 47.5 ± 12.5%, p < 0.01). There was no peri-strut inflammation in any of the groups. However, the endothelialisation score was numerically not meaningfully decreased in ed-frSES (ed-frSES: 2.93 vs. frSES: 3. vs. BMS: 3, p = 0.05). Signs of fibrin were also noted in ed-frSES (ed-frSES: 0.4 vs. frSES: 0 vs. BMS: 0, p = 0.05).
  
  
  CONCLUSIONS
  Sirolimus dose-dependent vascular response was reported. The elevated dose, fast releasing SES shows satisfactory vascular healing, similar to regular dose, fast release SES, with improved efficacy in restenosis inhibition.
authors.affiliation: Centre for Cardiovascular Research and Development, American Heart of Poland SA, Katowice, Poland. p.buszman@ahp-ccrd.org.
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Buszman
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Orlik
authors.forename: Jacek
authors.initials: J
authors.lastname: Pająk
authors.forename: Michał
authors.initials: M
authors.lastname: Jelonek
authors.forename: Agata
authors.initials: A
authors.lastname: Krauze
authors.forename: Adam
authors.initials: A
authors.lastname: Janas
authors.forename: Jacek
authors.initials: J
authors.lastname: Legutko
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wojakowski
authors.forename: Paweł E
authors.initials: PE
authors.lastname: Buszman
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Milewski
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D023903:Coronary Restenosis / Q000473:pathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D054855:Drug-Eluting Stents; D007249:Inflammation; D023421:Models, Animal; D020123:Sirolimus / Q000494:pharmacology*; D013552:Swine
chemical_list: D020123:Sirolimus
keywords: biodegradable polymer; fast release; porcine coronary model; sirolimus eluting stent