title: Biological effect on drug distribution and vascular healing via paclitaxel-coated balloon technology in drug eluting stent restenosis swine model.
abstract: OBJECTIVE
  To evaluate the biological effect of a paclitaxel-coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES-ISR) swine model.
  
  
  BACKGROUND
  The mechanism of action and healing response via PCB technology in DES-ISR is not completely understood.
  
  
  METHODS
  A total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in-stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES-ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT).
  
  
  RESULTS
  The paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr Cmax , and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES-ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES-ISR + PCB group displayed higher levels of peri-strut inflammation and fibrin scores compared to the -limus DES-ISR + PCB group.
  
  
  CONCLUSIONS
  In ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES-ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Bard Lutonix Inc., New Hope, Minnesota.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Alizée Pathology, Thurmont, Maryland.
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.affiliation: Alizée Pathology, Thurmont, Maryland.
authors.forename: Serge D
authors.initials: SD
authors.lastname: Rousselle
authors.affiliation: Alizée Pathology, Thurmont, Maryland.
authors.forename: Krista N
authors.initials: KN
authors.lastname: Dillon
authors.affiliation: Alizée Pathology, Thurmont, Maryland.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Garza
authors.affiliation: Bard Lutonix Inc., New Hope, Minnesota.
authors.forename: Chris
authors.initials: C
authors.lastname: Barry
authors.affiliation: Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
mesh_terms: D000818:Animals; D006328:Cardiac Catheterization / Q000295:instrumentation*; D062906:Cardiac Catheters; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004864:Equipment and Supplies; D005337:Fibrin / Q000378:metabolism; D008670:Metals; D058426:Neointima; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation*; D015607:Stents; D013552:Swine; D014018:Tissue Distribution; D041623:Tomography, Optical Coherence; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D008670:Metals; D005337:Fibrin; D017239:Paclitaxel
keywords: drug eluting balloon; in-stent restenosis; pharmacokinetics; preclinical coronary model