Human-grade purified collagenase for the treatment of experimental arterial chronic total occlusion

• Published in: Cardiovascular revascularization medicine 2005-04, Vol.6 (2), p.65-69
• Main Authors: Segev, Amit, Nili, Nafiseh, Qiang, Beiping, Charron, Thierry, Butany, Jagdish, Strauss, Bradley H.
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon - methods; Animal model; Animals; Arterial Occlusive Diseases - drug therapy; Arterial Occlusive Diseases - surgery; Blotting, Western - methods; Chronic Disease; Chronic total occlusion; Collagenase; Collagenases - administration & dosage; Collagenases - therapeutic use; Collagenases - toxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme; Femoral Artery - physiopathology; Femoral Artery - surgery; Gelatinases - drug effects; Male; Rabbits; Time Factors; Treatment Outcome
• ISSN: 1553-8389; 1878-0938
• DOI: 10.1016/j.carrev.2005.05.007

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. A chronic total arterial occlusion was constructed in femoral arteries of New Zealand white rabbits. The local administration of purified collagenase solution (150 μg) 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 μg) 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. 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.