title: Natural history of experimental arterial chronic total occlusions.
abstract: OBJECTIVE
  We sought to perform the first systematic study of the natural history of chronic total arterial occlusions (CTOs) in an experimental model.
  
  
  BACKGROUND
  Angioplasty of CTOs has low success rates. The structural and perfusion changes during CTO maturation, which may adversely affect angioplasty outcome, have not been systematically studied.
  
  
  METHODS
  Occlusions were created in 63 rabbit femoral arteries by thrombin injection. Histology, contrast-enhanced magnetic resonance imaging, relative blood volume (RBV) index, and micro-computed tomography imaging were analyzed at 2, 6, 12, and 18 to 24 weeks.
  
  
  RESULTS
  Early changes were characterized by an acute inflammatory response and negative arterial remodeling, with >70% reduction of arterial cross-sectional area (CSA) from 2 to 6 weeks. Intraluminal neovascularization of the CTO occurred with a 2-fold increase in total (media + intima) microvessel CSA from 2 to 6 weeks (0.014 +/- 0.002 mm2 to 0.023 +/- 0.005 mm2, p = 0.0008) and a 3-fold increase in RBV index (5.1 +/- 1.9% to 16.9 +/- 2.7%, p = 0.0008). However at later time periods, there were significant reductions in both RBV (3.5 +/- 1.1%, p < 0.0001) and total microvessel CSA (0.017 +/- 0.002 mm2, p = 0.011). Micro-computed tomography imaging demonstrated a corkscrew-like recanalization channel at the proximal end at 6 weeks that regressed at later time points. These vascular changes were accompanied by a marked decrease in proteoglycans and accumulation of a collagen-enriched extracellular matrix, particularly at the entrance ("proximal fibrous cap").
  
  
  CONCLUSIONS
  This study is the first to systematically analyze compositional changes occurring during CTO maturation, which may underlie angioplasty failure. Negative remodeling, regression of intraluminal channels, and CTO perfusion, together with the accumulation of dense collagen, may represent important targets for novel therapeutic interventions.
authors.affiliation: Schulich Heart Programme, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Ronen
authors.initials: R
authors.lastname: Jaffe
authors.forename: General
authors.initials: G
authors.lastname: Leung
authors.forename: Nigel R
authors.initials: NR
authors.lastname: Munce
authors.forename: Amandeep S
authors.initials: AS
authors.lastname: Thind
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.forename: Kevan J T
authors.initials: KJ
authors.lastname: Anderson
authors.forename: Xiuling
authors.initials: X
authors.lastname: Qi
authors.forename: Judy
authors.initials: J
authors.lastname: Trogadis
authors.forename: Ariella
authors.initials: A
authors.lastname: Nadler
authors.forename: Davida
authors.initials: D
authors.lastname: Shiff
authors.forename: Jamie
authors.initials: J
authors.lastname: Saperia
authors.forename: Julia
authors.initials: J
authors.lastname: Lockwood
authors.forename: Chaim
authors.initials: C
authors.lastname: Jacobs
authors.forename: Beiping
authors.initials: B
authors.lastname: Qiang
authors.forename: Aaron
authors.initials: A
authors.lastname: Teitelbaum
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Dick
authors.forename: John D
authors.initials: JD
authors.lastname: Sparkes
authors.forename: Jagdish
authors.initials: J
authors.lastname: Butany
authors.forename: Graham A
authors.initials: GA
authors.lastname: Wright
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss