Published Online
on August 25, 2003

A more recent version of this article appeared on September 9, 2003

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Submitted on October 30, 2002
Revised on May 13, 2003
Accepted on May 14, 2003

Collagenase Plaque Digestion for Facilitating Guide Wire Crossing in Chronic Total Occlusions

Bradley H. Strauss MD, PhD^*, Lorne Goldman MD, Beiping Qiang MD, Nafiseh Nili PhD, Amit Segev MD, Jagdish Butany MD, John D. Sparkes MSc, Zane S. Jackson PhD, Mohammad R. Eskandarian MD, and Renu Virmani MD

From the Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St Michael's Hospital, Toronto, Ontario, Canada; University Health Network (J.B.), University of Toronto, Ontario, Canada; and Armed Forces Institute of Pathology (R.V.), Bethesda, Md.

^* To whom correspondence should be addressed. E-mail: straussb{at}smh.toronto.on.ca.

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.

Methods and Results--Type IA collagenase (100 or 450 µg) 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.

Key words: angioplasty • occlusion • collagen

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