title: Collagenase plaque digestion for facilitating guide wire crossing in chronic total occlusions.
abstract: BACKGROUND
  Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO.
  
  
  RESULTS
  Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments.
  
  
  CONCLUSIONS
  Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.
authors.affiliation: Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St Michael's Hospital, Toronto, Ontario, Canada. straussb@smh.toronto.on.ca
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
authors.forename: Lorne
authors.initials: L
authors.lastname: Goldman
authors.forename: Beiping
authors.initials: B
authors.lastname: Qiang
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Nili
authors.forename: Amit
authors.initials: A
authors.lastname: Segev
authors.forename: Jagdish
authors.initials: J
authors.lastname: Butany
authors.forename: John D
authors.initials: JD
authors.lastname: Sparkes
authors.forename: Zane S
authors.initials: ZS
authors.lastname: Jackson
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Eskandarian
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D000792:Angiography; D000818:Animals; D002908:Chronic Disease; D017364:Collagenases / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008026:Ligation; D008297:Male; D003012:Microbial Collagenase / Q000008:administration & dosage / Q000009:adverse effects; D011817:Rabbits; D011897:Random Allocation; D013917:Thrombin; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D013917:Thrombin; D017364:Collagenases; D003012:Microbial Collagenase