Human-grade purified collagenase for the treatment of experimental arterial chronic total occlusion.
OBJECTIVE
Chronic total occlusions (CTO) remain a major limitation of percutaneous interventions. Procedural failure is usually due to the inability to cross the lesion with a guide wire. We have previously shown that local administration of a laboratory-grade collagenase followed by a 72-h waiting period may facilitate guide-wire crossing. The aim of the present study was to evaluate the efficacy and toxicity of a human-grade purified collagenase, suitable for clinical use, in facilitating guide-wire crossing in a rabbit model of femoral artery CTO.


RESULTS
A chronic total arterial occlusion was constructed in femoral arteries of New Zealand white rabbits. The local administration of purified collagenase solution (150 microg) via an over-the-wire balloon system was performed in 10 CTO. Guide-wire crossing was attempted after 24 h and was successful in all cases. Different doses (50-500 microg) were administered to an additional 17 rabbits to assess collagenase effects. Local subcutaneous bruising was observed at higher doses. Histological evaluation showed no damage to the arterial wall structure. Arterial extracts from collagenase-treated arteries showed increased MMP-2 and MMP-9 activities and higher levels of local MMP-1 and degraded collagen.


CONCLUSIONS
Local administration of a human-grade purified collagenase degrades collagen in CTO and is highly effective for the facilitation of guide-wire crossing in CTO.
Segev
Amit
A
Roy and Ann Foss Cardiovascular Research Program, Terrence-Donnelly Heart Center, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Nili
Nafiseh
N
Qiang
Beiping
B
Charron
Thierry
T
Butany
Jagdish
J
Strauss
Bradley H
BH
D000800:Angioplasty, Balloon / Q000379:methods; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000601:surgery; D015153:Blotting, Western / Q000379:methods; D002908:Chronic Disease; D017364:Collagenases / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000503:physiopathology / Q000601:surgery; D018093:Gelatinases / Q000187:drug effects; D008297:Male; D011817:Rabbits; D013997:Time Factors; D016896:Treatment Outcome
D017364:Collagenases; D018093:Gelatinases