title: A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon.
abstract: OBJECTIVE
  Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound.
  
  
  METHODS
  A 140 μg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drug-delivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period.
  
  
  RESULTS
  The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies.
  
  
  CONCLUSIONS
  RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis.
authors.affiliation: Surgical Department, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Presidio Ospedaliero Capitanio, Milan, Italy; Dipartimento di Scienze della Salute, University of Milan-Bicocca, Milan, Italy. Electronic address: v.tolva@auxologico.it.
authors.forename: Valerio
authors.initials: V
authors.lastname: Tolva
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica, Università degli Studi di Milano, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mazzola
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Zerbi
authors.affiliation: Surgical Department, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Presidio Ospedaliero Capitanio, Milan, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Casana
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica, Università degli Studi di Milano, Milan, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Albertini
authors.affiliation: Department and Laboratory of Cardiac Arrhtmias on Genetic Basis, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calvillo
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cilurzo
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects* / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D004867:Equipment Design; D006801:Humans; D006965:Hyperplasia; D007083:Iliac Artery / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima; D011817:Rabbits; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D062666:Vascular Access Devices; D057772:Vascular System Injuries / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D013267:Stilbenes; D000077185:Resveratrol